Heart Rhythm Association (EHRA), European · 11/5/2018 · Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 11Centre for Heart Rhythm Disorders, South Australian

2018 Joint European consensus document on

the management of antithrombotic therapy in

atrial fibrillation patients presenting with acute

coronary syndrome andor undergoing

percutaneous cardiovascular interventions a

joint consensus document of the European

Heart Rhythm Association (EHRA) European

Society of Cardiology Working Group on

Thrombosis European Association of

Percutaneous Cardiovascular Interventions

(EAPCI) and European Association of Acute

Cardiac Care (ACCA) endorsed by the Heart

Rhythm Society (HRS) Asia-Pacific Heart

Rhythm Society (APHRS) Latin America

Heart Rhythm Society (LAHRS) and Cardiac

Arrhythmia Society of Southern Africa

(CASSA)

Gregory YH Lip (Chair)123 Jean-Phillippe Collet (Co-Chair)4 Michael Haude

(Co-Chair)5 Robert Byrne67 Eugene H Chung8 Laurent Fauchier9

Sigrun Halvorsen10 Dennis Lau11 Nestor Lopez-Cabanillas12 Maddalena Lettino13

Francisco Marin14 Israel Obel15 Andrea Rubboli16 Robert F Storey17

Marco Valgimigli18 and Kurt Huber (Co-Chair)19

Corresponding author Tel thorn44 121 5075080 E-mail address gyhlipbhamacuk

Europace EHRA CONSENSUS DOCUMENTdoi101093europaceeuy174

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ESC Scientific Document Group Tatjana Potpara (Review Coordinator)20

Carina Blomstrom Lundqvist21 Harry Crijns22 Jan Steffel23 Hein Heidbuchel24

Goran Stankovic25 Juhani Airaksinen26 Jurrien M Ten Berg27 Davide Capodanno28

Stefan James29 Hector Bueno3031 Joao Morais32 Dirk Sibbing33 Bianca Rocca34

Ming-Hsiung Hsieh35 Nazem Akoum36 Deborah J Lockwood37

Jorge Rafael Gomez Flores38 Ronald Jardine39

1Institute of Cardiovascular Sciences University of Birmingham UK 2Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart amp Chest HospitalLiverpool UK 3Department of Clinical Medicine Aalborg Thrombosis Research Unit Aalborg University Aalborg Denmark 4Sorbonne Universite Paris 6 ACTION StudyGroup (wwwaction-coeurorg) Institut de Cardiologie Hopital Pitie-Salpetriere (APHP) INSERM UMRS Paris France 5Stadtische Kliniken Neuss Lukaskrankenhaus GmbhKardiologie Nephrologie Pneumologie Neuss Germany 6Deutsches Herzzentrum Muenchen Munich Germany 7DZHK (German Centre for Cardiovascular Research)partner site Munich Heart Alliance Munich Germany 8University of North Carolina at Chapel Hill Medicine Cardiology Electrophysiology Chapel Hill NC USA 9CentreHospitalier Universitaire Trousseau et Faculte de MedecinemdashUniversite Francois Rabelais Tours France 10Department of Cardiology Oslo University Hospital Ulleval andInstitute of Clinical Medicine University of Oslo Oslo Norway 11Centre for Heart Rhythm Disorders South Australian Health and Medical Research Institute University ofAdelaide and Royal Adelaide Hospital Adelaide Australia 12Clinica Adventista Belgrano Instituto Del Corazon Buenos Aires Argentina 13Cardiology Department HumanitasResearch Hospital Rozzano MI Italy 14Department of Cardiology Hospital Universitario Virgen de la Arrixaca Murcia Spain 15Milpark Hospital Cardiology Unit JohannesburgSouth Africa 16Division of Cardiology Laboratory of Interventional Cardiology Ospedale Maggiore Bologna Italy 17Department of Infection Immunity and Cardiovascular DiseaseUniversity of Sheffield Sheffield UK 18Inselspital Cardiology Bern Switzerland 193rd Department of Medicine Cardiology and Intensive Care Medicine Wilhelminenhospital ViennaVienna Austria 20School of Medicine Belgrade University Cardiology Clinic Clinical Centre of Serbia Belgrade Serbia 21Department of Medical Science and Cardiology UppsalaUniversity Uppsala Sweden 22Cardiology Department Maastricht UMCthorn Maastricht Netherlands 23University Heart Center Zurich Zurich Switzerland 24Antwerp Universityand University Hospital Antwerp Belgium 25Department of Cardiology Clinical Center of Serbia Belgrade Serbia 26Turku University Hospital Cardiology Department of InternalMedicine Turku Finland 27St Antonius Hospital Cardiology Department Nieuwegein Netherlands 28Ferrarotto Hospital Azienda Ospedaliero-Univ Policlinico-VittorioEmanuele University of Catania Cardiologia Department University of Catania Catania Italy 29Department of Medical Sciences and Uppsala Clinical Research Center UppsalaUniversity Senior Interventional Cardiologist Uppsala University Hospital Uppsala Sweden 30Centro Nacional de Investigaciones Cardiovasculares (CNIC) Melchor FernandezAlmagro Madrid Spain 31Department of Cardiology Hospital Universitario 12 de Octubre Madrid Spain 32Department of Cardiology Leiria Hospital Centre Portugal33Oberarzt Medizinische Klinik und Poliklinik I Ludwig-Maximilians-Universitat (LMU) Campus Groszlighadern Munchen Germany 34Department of Pharmacology Catholic UniversitySchool of Medicine Rome Italy 35Taipei Medical University Taipei Taıwan 36Cardiology Department University of Washington Seattle USA 37OU Heart Rhythm Institute OUHealth Sciences Center Oklahoma USA 38Instituto Nacional de Cardiologia I Chavez Electrofisiologia Mexico DF Mexico and 39Linmed Hospital Benoni South Africa

Received 25 June 2018 editorial decision 28 June 2018 accepted 28 June 2018

In 2014 a joint consensus document dealing with the management of antithrombotic therapy in atrial fibrillation(AF) patients presenting with acute coronary syndrome (ACS) andor undergoing percutaneous coronary or valveinterventions was published which represented an effort of the European Society of Cardiology Working Group onThrombosis European Heart Rhythm Association (EHRA) European Association of Percutaneous CardiovascularInterventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart RhythmSociety (HRS) and Asia-Pacific Heart Rhythm Society (APHRS) Since publication of this document additional datafrom observational cohorts randomized controlled trials and percutaneous interventions as well as new guidelineshave been published Moreover new drugs and devicesinterventions are also available with an increasing evidencebase The approach to managing AF has also evolved towards a more integrated or holistic approach In recognizingthese advances since the last consensus document EHRA WG Thrombosis EAPCI and ACCA with additionalcontributions from HRS APHRS Latin America Heart Rhythm Society (LAHRS) and Cardiac Arrhythmia Society ofSouthern Africa (CASSA) proposed a focused update to include the new data with the remit of comprehensivelyreviewing the available evidence and publishing a focused update consensus document on the management ofantithrombotic therapy in AF patients presenting with ACS andor undergoing percutaneous coronary or valveinterventions and providing up-to-date consensus recommendations for use in clinical practice

Keywords European Heart Rhythm Association bull Consensus document bull Position paper bull Atrial fibrillation bull Acutecoronary syndrome bull Coronary artery disease bull Myocardial infarction bull Percutaneous coronaryintervention bull Stent bull Antithrombotic therapy bull Antiplatelet agents bull Anticoagulation bull Vitamin Kantagonists bull Non-vitamin K antagonist oral anticoagulants bull Low molecular weight heparin bull Parenteralanticoagulants bull Left atrial appendage occlusion bull Stroke bull Thromboembolism bull Thrombosis bull Bleeding

Table of Contents

Introduction 3Evidence review 3

An overview of new data since last version of the document 3

Observational cohorts 3New randomized controlled trials on antithrombotic therapy 4

Oral anticoagulants 4Antiplatelet drugs 5Parenteral anticoagulants 7

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Stents in patients with increased bleeding risk 7Other data in structural interventions ie valve interventions(TAVI mitral) LAA closure 8

Assessing stroke and bleeding risks 10Optimizing management 11

Elective PCI 11Acute management 12

Post-procedural and post-discharge therapy 16Long-term management 18

Areas for future research 22

Introduction

In 2014 a joint consensus document dealing with the management ofantithrombotic therapy in atrial fibrillation (AF) patients presentingwith acute coronary syndrome (ACS) andor undergoing percutane-ous coronary (PCI) or valve interventions was published which rep-resented an effort of the European Society of Cardiology WorkingGroup on Thrombosis European Heart Rhythm Association(EHRA) European Association of Percutaneous CardiovascularInterventions (EAPCI) and European Association of Acute CardiacCare (ACCA) endorsed by the Heart Rhythm Society (HRS) andAsia-Pacific Heart Rhythm Society (APHRS)1 Since publication ofthis document additional data from observational cohortsrandomized trials and percutaneous interventions have been pub-lished New guidelines on AF from the ESC2 and APHRS3 andEuropean ST-elevation myocardial infarction (STEMI) management4

as well as a focused update on dual antiplatelet therapy (DAPT)5

have been publishedThis year we saw publication of the 2018 update of the EHRA

practical guide on the use of non-vitamin K antagonist oral anticoagu-lants (NOACs) in patients with AF6 and we expect new AF guidelinesfrom North America from the American College of Chest Physicians(ACCP) and American College of Cardiology (ACC)AmericanHeart Association (AHA)Heart Rhythm Society (HRS)

We also recognized that the approach to managing AF has evolvedtowards an integrated or holistic approach with the three essentialcomponents of the patient management pathway as follows7 (i)Avoid stroke with Anticoagulation therapy (ii) Better symptom man-agement with a patient-centred symptom-directed decision makingwith regard to rate or rhythm control and (iii) Cardiovascular andcomobidity risk factor management ie addressing lifestyle changesand associated risks including hypertension sleep apnoea cardiac is-chaemia etc This has been referred to as the ABC (Atrial fibrillationBetter Care) pathway7

In recognizing these advances since the last consensus documentEHRA WG Thrombosis EAPCI and ACCA with additional contri-butions from HRS APHRS Latin America Heart Rhythm Society(LAHRS) and Cardiac Arrhythmia Society of Southern Africa(CASSA) proposed a focused update to include the new data withthe remit of comprehensively reviewing the available evidence andpublishing a focused update consensus document on the manage-ment of antithrombotic therapy in AF patients presenting with ACSandor undergoing PCI or valve interventions (eg transcatheteraortic valve replacement) and providing up-to-date consensus rec-ommendations for use in clinical practice However the ultimate

decision on management must be made between the healthcare pro-vider and the patient in light of all individual factors presented

Evidence reviewThis document was prepared by the Task Force with representationfrom EHRA WG Thrombosis EAPCI and ACCA with additionalcontributions from HRS APHRS LAHRS and CASSA and peer-reviewed by official external reviewers representing all these bodiesTheir members made a detailed literature review weighing thestrength of evidence for or against a specific treatment or procedureand including estimates of expected health outcomes where data ex-ist In controversial areas or with respect to issues without evidenceother than usual clinical practice a consensus was achieved by agree-ment of the expert panel after thorough deliberation

We opted for an easier and user-friendly system of ranking usinglsquocoloured heartsrsquo that should allow physicians to easily assess the cur-rent status of the evidence and consequent guidance (Table 1) ThisEHRA grading of consensus statements does not have separate defi-nitions of the level of evidence This categorization used for consen-sus statements must not be considered as directly similar to thatused for official society guideline recommendations which apply aclassification (Class I-ndashIII) and level of evidence (A B and C) to rec-ommendations used in official guidelines

Thus a green heart indicates a lsquoshould do thisrsquo consensus state-ment or indicated treatment or procedure that is based on at leastone randomized trial or is supported by strong observational evi-dence that it is beneficial and effective A yellow heart indicates gen-eral agreement andor scientific evidence favouring a lsquomay do thisrsquostatement or the usefulnessefficacy of a treatment or procedure Alsquoyellow heartrsquo symbol may be supported by randomized trials basedon a small number of patients or which is not widely applicableTreatment strategies for which there is scientific evidence of poten-tial harm and should not be used (lsquodo not do thisrsquo) are indicated by ared heart

An overview of new data since lastversion of the document

Observational cohortsSince the publication of the previous consensus document at least30 observational reports on patients on oral anticoagulation (OAC)presenting with ACS andor undergoing PCI have been published8ndash37

(Supplementary material online Table Sw1)A total of 171 026 patients have been included with AF being the

most frequent albeit not the only indication for OAC For 29 418patients information on the different antithrombotic strategies wasprovided 7656 (26) received triple antithrombotic therapy (TAT)of OAC aspirin and a P2Y12-receptor inhibitor (generally clopidog-rel) 21 279 (72) DAPT of aspirin and P2Y12-receptor inhibitor(generally clopidogrel) and 483 (2) dual antithrombotic therapy(DAT) of OAC and either aspirin or clopidogrel In all studies exceptthree141521 where approximately 50 39 and 8 of patients re-spectively received a NOAC as part of the antithrombotic regimenOAC consisted of a vitamin K-antagonist (VKA) generally warfarin(Supplementary material online Table Sw1) Indication for PCI

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included in most cases either ACS or stable coronary artery disease(CAD) The majority were retrospective analyses of either small-sizedatabases or large multicentre nationwide registries that had gener-ally been set up for other purposes In only a few cases the data werederived from prospective observational registries specificallydesigned to evaluate the management strategies and outcomes ofOAC patients undergoing PCI Length of follow-up was variableranging from in-hospital to 6 years (Supplementary material onlineTable Sw1) between 1999 and 2015

Overall TAT was consistently associated with a significantly in-creased risk of total andor major bleeding compared with otherantithrombotic regimens The risk of (major) bleeding may be in-versely related to the quality of OAC measured as time in therapeu-tic range (TTR) for patients receiving a VKA8 The bleeding riskprofile may impact on the occurrence of major bleeding more thanthe antithrombotic combination10 The rates of major adverse car-diovascular and cerebrovascular events (MACCE) were similar irre-spective of the antithrombotic regimen andor use of OAC

The limitations of these studies include the lack of randomizationand associated selection bias in the prescription of the various antith-rombotic regimens as well as the lack of systematic bleeding risk as-sessment incomplete information on adherence to treatment andTTR values the independent contribution of periprocedural manage-ment on the occurrence of MACCE and bleeding and the alterationsin the prescribed antithrombotic therapy subsequent to an ischaemicor haemorrhagic event

In patients with CHA2DS2-VASc [congestive heart failure hyper-tension age gt_75 (doubled) diabetes stroke (doubled)-vascular dis-ease age 65ndash74 and sex category (female)] score 1 when comparedwith gt_2 the efficacy of TAT in the prevention of stroke andor sys-temic embolism was not statistically superior to DAPT22

(Supplementary material online Table Sw1) In general these data

have to be interpreted with caution as this registry study was smalland not randomized The use of the newer more potent P2Y12-receptor inhibitors prasugrel and ticagrelor as part of a TAT regimehas been associated with an increased risk of bleeding events Nospecific information on the relative efficacy and safety of NOACs ei-ther as a category or as individual agents can be derived from avail-able observational data Further data are expected to come from theobservational multicentre AVIATOR 2 registry38 This study wascapped after including 500 (of the originally planned 2500) AFpatients undergoing PCI and evaluates MACCE and bleeding rates

New randomized controlled trials onantithrombotic therapyOral anticoagulants

Since publication of the 2014 consensus document two randomizedcontrolled trials on NOAC vs VKA in combination with antiplateletsfor patients with AF undergoing PCI have been published primarily in-vestigating safety3940 and at least two large trials are ongoing

In the randomized PIONEER AF PCI trial (Open-LabelRandomized Controlled Multicenter Study Exploring TwoTreatment Strategies of Rivaroxaban and a Dose-Adjusted OralVitamin K Antagonist Treatment Strategy in Subjects with AtrialFibrillation who Undergo Percutaneous Coronary Intervention)2124 participants with non-valvular AF who had undergone PCI withstenting (about 30 of patients had a troponin-positive ACS andabout 20 had unstable angina as index event) were randomlyassigned to DAT with lsquolow-dosersquo rivaroxaban [15 mg od (once daily)]plus a P2Y12 inhibitor for 12 months (Group 1) novel TAT withlsquovery-low-dosersquo rivaroxaban [25 mg bid (twice daily)] plus DAPT for1 6 or 12 months (Group 2) or standard therapy with a dose-adjusted VKA (od) plus DAPT for 1 6 or 12 months (Group 3)39

Table 1 Scientific rationale of recommendationsa

Definitions where related to a treatment or

procedure

Consensus statement

instruction

Symbol

Scientific evidence that a treatment or procedure is

beneficial and effective Requires at least one ran-

domized trial or is supported by strong observa-

tional evidence and authorsrsquo consensus (as indicated

by an asterisk)

lsquoShould do thisrsquo

General agreement andor scientific evidence favour

the usefulnessefficacy of a treatment or procedure

May be supported by randomized trials based on a

small number of patients or which is not widely

applicable

lsquoMay do thisrsquo

Scientific evidence or general agreement not to use or

recommend a treatment or procedure

lsquoDo not do thisrsquo

aThis categorization for our consensus document should not be considered as being directly similar to that used for official society guideline recommendations which apply aclassification (IndashIII) and level of evidence (A B and C) to recommendations

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The primary endpoint of the trial was clinically-significant bleedingThe rates of clinically-significant bleeding were lower in the twogroups receiving rivaroxaban than in the group receiving standardtherapy (168 in Group 1 180 in Group 2 and 267 in Group 3P lt 0001 for both comparisons) There were no statistically signifi-cant differences in the rates of death from cardiovascular causesmyocardial infarction (MI) or stroke although the study was notpowered for efficacy and the observed broad confidence intervals(CIs) diminish the surety of any conclusions No power calculation inthis exploratory trial recruitment was not event-driven and thatprior stroke was an exclusion criteria (which led to the selection oflow risk patients)

In the Randomized Evaluation of Dual Antithrombotic TherapyWith Dabigatran vs Triple Therapy With Warfarin in Patients WithNonvalvular Atrial Fibrillation Undergoing Percutaneous CoronaryIntervention (RE-DUAL PCI) study3940 DAT with dabigatran etexi-late (110 or 150 mg bid) and a P2Y12 inhibitor (either clopidogrel orticagrelor) was compared with TAT with warfarin a P2Y12 inhibitor(either clopidogrel or ticagrelor) and low-dose aspirin (for 1 or3 months depending on stent type) in 2725 non-valvular AF patientswho had undergone PCI with stenting The primary endpoint wasmajor or clinically-relevant non-major bleeding during follow-up asdefined by the International Society on Thrombosis and Hemostasis(ISTH) The trial also tested for the non-inferiority of dual therapywith dabigatran (both doses combined) to TAT with warfarin withrespect to the incidence of a composite efficacy Endpoint of throm-boembolic events (MI stroke or systemic embolism) death orunplanned revascularization Approximately half of the patients hadan ACS Most of the patients received clopidogrel as the P2Y12 inhibi-tor only 120 received ticagrelor Drug-eluting stents alone wereused in 826 of the patients

In RE-DUAL PCI the incidence of the primary endpoint was 154in the 110-mg DAT group when compared with 269 in the TATgroup [hazard ratio (HR) 052 95 CI 042ndash063 P lt 0001 for non-inferiority P lt 0001 for superiority] and 202 in the 150-mg DATgroup when compared with 257 in the corresponding TAT groupwhich did not include elderly patients outside the United States (HR072 95 CI 058ndash088 P lt 0001 for non-inferiority) The incidenceof the composite efficacy endpoint was 137 in the two DAT groupscombined when compared with 134 in the TAT group (HR 10495 CI 084ndash129 P = 0005 for non-inferiority) When looking at thetwo dabigatran groups separately there was a non-significant excessin the number of ischaemic events (ie stent thrombosis and MI) withthe 110 mg bid dose compared with TAT

Apixaban has been shown to have similar beneficial effects onstroke or systemic embolism and major bleeding compared withwarfarin irrespective of concomitant aspirin use41 However nocompleted trial has studied apixaban as part of dual or triple therapyin patients with AF and ACS or PCI The ongoing AUGUSTUS study(NCT02415400) is an open-label 2 2 factorial randomized con-trolled non-inferiority clinical trial to evaluate the safety of apixaban(standard dosing) vs VKA and aspirin vs aspirin placebo in patientswith AF and ACS (the only trial including ACS patients treated con-servatively or by PCI)42 The primary focus is a comparison of thebleeding risk of apixaban with or without aspirin vs a VKA such as

warfarin with or without aspirin This study will include 4600 patientsand enrolment was completed in April 2018 (Table 2) The EdoxabanTreatment vs Vitamin K Antagonist in Patients With AtrialFibrillation Undergoing Percutaneous Coronary Intervention(ENTRUST-AF-PCI 1500 patients are planned) study is designed toevaluate the safety and to explore the efficacy of an edoxaban-based(standard dosing) antithrombotic regimen vs a VKA-based antith-rombotic regimen in subjects with AF following PCI with stent place-ment43 In both the AUGUSTUS and the ENTRUST-AF-PCI study(again both being safety studies not sufficiently powered for ischae-mic outcomes) standard dosing of NOAC is used in combinationwith antiplatelets with dose reduction only in selected patients fulfill-ing NOAC specific dose reduction criteria

In a systematic review and meta-analysis of four randomized clini-cal trials including 5317 patients [3039 (57) received DAT]Thrombolysis in Myocardial Infarction (TIMI) major or minor bleed-ing showed a reduction by 47 in the DAT arm compared with theTAT arm (43 vs 90 HR 053 95 CI 036ndash085)44 There was nodifference in the major adverse cardiac events (MACE) (104 vs100 HR 085 95 CrI 048ndash129) or in individual outcomes of all-cause mortality cardiac death MI stent thrombosis or stroke be-tween DAT and TAT

Antiplatelet drugs

The WOEST study initially tested the concept of dropping aspirin af-ter PCI and using a combination of clopidogrel and warfarin alonesuggesting that this approach is effective and safe in terms of throm-botic events and reduced overall bleeding risk45 As discussed abovethe PIONEER and RE-DUAL trials3940 further reinforce the conceptof potential redundancy of aspirin and its associated bleeding hazardin AF patients treated with anticoagulant and P2Y12 inhibitor

Although in a non-AF population the GEMINI-ACS-1 study hasreinforced the concept that oral anticoagulation may substitute foraspirin in patients who are stable early after PCI showing that rivar-oxaban combined with either clopidogrel or ticagrelor provided simi-lar efficacy in prevention of ischaemic events compared with aspirinwith either of these P2Y12 inhibitors46 The COMPASS study demon-strated higher efficacy of rivaroxaban 25 mg bid plus aspirin 100 mgod in long-term prevention of ischaemic events vs aspirin alone in anon-AF vascular disease population This was accompanied by higherbleeding complications when compared with aspirin alone and doesnot support the suggestion that aspirin can be substituted by anOAC47 The GLOBAL-LEADERS study is assessing amongst otherconcepts whether ticagrelor monotherapy from 1 month after PCI issuperior to standard DAPT and will further define the necessity of as-pirin from this timepoint in a non-AF population48 TWILIGHT is thelargest study to date that is designed and powered in order to dem-onstrate a lower bleeding rate with ticagrelor monotherapy vs tica-grelor plus acetylsalicylic acid (ASA) beyond 3 months post-procedure in a high-risk patient population undergoing PCI withdrug-eluting stents (DES)49

Overall limited numbers of patients have been studied with thecombination of an anticoagulant and either prasugrel or ticagre-lor232850 Because of the greater platelet inhibition with approveddoses of prasugrel or ticagrelor compared with clopidogrel the risk

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of spontaneous bleeding is higher when used in combination withaspirin5152

The PEGASUS-TIMI 54 study assessed a lower dose of ticagrelor(60 mg bid) in addition to the 90 mg bid dose licensed for use in ACSin combination with aspirin (75ndash150 mg od) in non-AF patients within1ndash3 years of MI and at higher risk of recurrent atherothromboticevents53 Both doses of ticagrelor had similar efficacy and safety al-though there were numerical trends suggesting less minor bleedingand better tolerability with ticagrelor 60 mg bid54 Interestingly theextent of platelet inhibition with ticagrelor 60 mg bid was similar tothat achieved with ticagrelor 90 mg bid55 The TROPICAL-ACS studysuggested that guided de-escalation from prasugrel to clopidogrel (inclopidogrel responders) after PCI is non-inferior to continuing prasu-grel in a DAPT strategy56 Another de-escalation trial (TOPIC) com-pared a switch from DAPT (aspirin plus a new P2Y12-inhibitor) withconservative DAPT (aspirin plus clopidorel) 1 month after ACS or tocontinue their initial drug regimen (unchanged DAPT)57 Theseauthors reported that switched DAPT is superior to an unchangedDAPT strategy to prevent bleeding complications without increase inischaemic events following ACS although these studies were notpowered to compare ischaemic event rates However the implica-tions of poor response to clopidogrel in patients treated with clopi-dogrel and an anticoagulant rather than aspirin are not wellcharacterized

Parenteral anticoagulants

Recent meta-analysis of 2325 VKA-treated AF patients undergoingcoronary angiography with or without PCI showed that bothbleeding and 30-day major adverse cardiovascular event rates weresimilar between those with interrupted or uninterrupted VKA58

However those who received parenteral bridging anticoagulants oninterruption of VKA had higher major bleeding rates58 The abovedata confirm recommendations of uninterrupted anticoagulation forelective PCI1 At present little is known regarding the bleedingand MACCE rates with continuation or interruption of NOAC dur-ing PCI

Limited data exists to guide the choice of and the dose of paren-teral anticoagulants whether unfractionated heparin (UFH) bivaliru-din or enoxaparin and their optimal dosages specific to AF patientsalready taking OAC when undergoing PCI for ACS Additional paren-teral anticoagulants may not be needed particularly if the interna-tional normalized ratio (INR) is more than 25 at the time of electivePCI159 On the other hand the usage of parenteral anticoagulantsduring PCI is recommended in AF patients on NOAC regardless ofthe timing of the last NOAC dose59

Stents in patients with increasedbleeding riskDrug-eluting and bare-metal stents

Since December 2014 three large-scale trials comparing differentstents have enrolled relatively high proportions of patients with AFrequiring treatment with OAC One trial enrolled patients regardedas being uncertain candidates for DES at the time60 About 12 hadOAC at discharge This pre-specified post hoc analysis of the ZEUStrial demonstrated that the use of the Endeavor zotarolimus-elutingstent is superior to bare-metal stents in terms of the composite of

death MI and target vessel revascularization (TVR) (HR 076 95 CI061ndash095 P = 0011) in patients at high bleeding risk (mainly triggeredby TVR)60 The median duration of DAPT was 1 month

Another prospective randomized trial enrolled patients at highbleeding risk and randomly allocated treatment with a polymer-freebiolimus A9-DES vs a bare-metal stent (LEADERS FREE trial)61 Themain finding was that the primary safety endpoint of death MI andstent thrombosis was reduced with the biolimus A9-DES (HR 07195 CI 056ndash091 P lt 0001 for non-inferiority and P = 0005 for su-periority) In line with expectations the primary efficacy endpoint oftarget lesion revascularization was reduced by half with the biolimusA9-DES (HR 050 95 CI 037ndash069 P lt 0001) while death as singleendpoint was not reduced Treatment effects were consistent inpatients with planned OAC therapy at discharge for efficacy andsafety endpoints

Subgroup analysis demonstrated similar outcome data for the biol-imus A9-DES vs bare-metal stents in elderly patients there was evi-dence of interaction with regard to treatment effect and diagnosis ofACS at baseline in relation to the primary safety endpoint (P = 004)with greater benefit for patients treated with the biolimus A9-DES62

Safety and efficacy were maintained during an extended follow-upout to 2 years even amongst the subgroup of patients who were can-didates for long term OAC6364

A more recent clinical trial compared the outcomes of elderlypatients (gt75 years) undergoing PCI with a new generation DES (bio-degradable polymer everolimus-eluting stents) compared with bare-metal stents (SENIOR trial) where 176 had AF at enrolment65

DAPT was recommended in both groups for the same duration1 month in patients with stable angina and 6 months in patients withACS The composite of death MI stroke or target lesionrevascularization was significantly reduced in patients treated withDES (relative risk 071 95 CI 052ndash094 P = 002) Bleeding was sim-ilar in both groups in line with the identical recommendations forantithrombotic treatment in both groups

Results with new-generation DES are generally excellent acrossthe spectrum of patient and lesion subgroups A recent systematic re-view of 158 trialsmdashconducted as part of a ESC-EAPCI task force onthe evaluation of coronary stentsmdashreported low rates of both reste-nosis and stent thrombosis at 9ndash12 months with new-generationDES (less than 5 and 1 respectively) with lower rates comparedwith both bare-metal stents and early-generation DES66 Large-scaleregistries support the generally high efficacy and safety of new-generation DES Convincing data to support different durations ofDAPT according to stent type are lacking and the general recommen-dation for 1-month DAPT after bare-metal stenting in stable patientsis not well supported More recently drug-eluting balloons can be analternative for stenting in special lesions (eg in patients with in-stentrestenosis)

The 2017 ESC Focused Update on Antiplatelet Therapy recom-mends that choice of duration of DAPT in patients should no longerbe differentiated on basis of device used ie whether the stentimplanted at time of PCI is a DES or bare-metal stent or whether adrug eluting balloon is used5 In view of the superior antirestenotic ef-ficacy and no signal of higher thrombotic risks even after short termDAPT duration of new generation DES when compared with BMS itis recommended that patients with AF undergoing PCI should betreated with new generation DES

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Bioresorbable scaffolds

Bioresobable scaffolds (BRS) are rarely used in clinical practice at pre-sent67 due to an increased risk of target lesion failure and devicethrombosis at 2ndash3 year follow-up and an excess of 1-year target ves-sel MI and stent thrombosis in comparison with conventional DES68

Consensus statements

Other data in structural interventionsie valve interventions (TAVI mitral)left atrial appendage closureTranscatheter aortic valve implantation

Cerebral embolization is one of the major complications that mightoccur in the very early phase of valve placement New periproceduralcerebral ischaemic defects have been reported in more than 60 ofpatients and clinically-apparent stroke occurs in around 3 of caseson average (range 0ndash6)69

Despite a higher incidence of cerebrovascular events with the firstdevices in the PARTNERS trials7071 there seems to be a similar riskof stroke in patients undergoing TAVI compared with patients receiv-ing the surgical aortic valve replacement (SAVR)72ndash75 Parenteralantithrombotic treatment during TAVI aims to prevent thrombo-embolic complications related to large catheter manipulation guide-wire insertion balloon aortic valvuloplasty and valve prosthesis im-plantation while minimizing the risk of bleeding particularly at thevascular access site Based on retrospective studies and randomizedtrials72737677 the most commonly used anticoagulant is UFH atdoses of 50ndash70 IUkg with a target activated clotting time (ACT) of250ndash300 s although no optimal ACT has been defined even in guide-lines78ndash82 Given the higher cost and similar efficacy of bivalirudinwhen compared with UFH the latter should remain the standard ofcare for patients undergoing TAVI unless contra-indications to UFHsuch as known heparin-induced thrombocytopenia exist83

Subacute cerebrovascular events associated with TAVI occur be-tween 24 h and 30 days while all the episodes occurring after 30 daysare defined as late Stroke rate at 30 days reported by randomizedclinical trials and registries ranges from 0 to 984 Factors poten-tially involved in such cerebrovascular events development arethrombogenicity of the valve apparatus exposure of the stent struts(expanded together with the valve) persistence of the perivalvularspace occupied by the native valve and the development of paroxys-mal atrial arrhythmias6982 Moreover the baseline risk for ischaemicand thromboembolic complications is further increased by comor-bidities including concomitant CAD which is present in 20ndash70 ofpatients and requires PCI in 20ndash40 of patients Furthermore AF isfound in about one-third of patients referred for TAVI707185ndash87

Prospective data on antithrombotic therapy after TAVI are stillscarce and recommendations regarding choice and optimal durationof antiplatelet or antithrombotic therapy are largely based on experi-ence from PCI and open-heart aortic valve replacement

Among patients without CAD and without AF the current stan-dard of care is still DAPT consisting of low-dose aspirin (75ndash100 mgper day) and clopidogrel 75 mg od (after loading dose of 300ndash600 mg) both started within 24 h prior to the intervention and con-tinued for 3ndash6 months followed by indefinite aspirin monotherapyPatients receiving single antiplatelet therapy soon after TAVI tendedto have a lower rate of major adverse events after the interventionwhen compared with patients on DAPT with a significant reductionof major and life-threatening bleeding complications at three monthsfollow-up88 A meta-analysis of the pooled results of this trial andother minor studies showed no benefit of DAPT in early stroke re-duction with a trend towards an increase in major bleeding thus sug-gesting the opportunity to adopt an antiplatelet monotherapy soonafter the intervention for all patients without indication foranticoagulation89

Other clinical trials are currently ongoing The AntiplateletTherapy for Patients Undergoing Transcatheter Aortic ValveImplantation (POPular TAVI n = 1000) trial is currently exploringwhether it is possible to skip clopidogrel in a larger population ofpatients undergoing TAVI with or without an indication for OACprior to the procedure Patients are randomized to aspirin alone vsaspirin plus clopidogrel for the first 3 months after the procedure andevaluated for the primary safety endpoint of freedom of non-procedure-related bleeding complications at 1 year follow-up Thecohort of patients for whom OAC is indicated (AF mechanical valveprostheses) is randomized to clopidogrel plus OAC vs OAC alone(NCT02247128)

The Global Study Comparing a rivAroxaban-basedAntithrombotic Strategy to an antiplatelet-based Strategy afterTranscatheter aortic vaLve rEplacement to Optimize ClinicalOutcome (Galileo n = 1520) study is an open-label multicentre ran-domized controlled trial actively recruiting patients undergoing TAVIwith no indication to permanent anticoagulant therapy Patientsassigned to the OAC arm are randomly assigned to receive 10 mg odrivaroxaban up to 25 months plus low-dose aspirin during the first 3months in order to assess whether this strategy is superior to DAPTwith aspirin plus clopidogrel (for 3 months) followed by aspirin alonein reducing death or first clinical thromboembolic events with no in-crease in bleeding complications (NCT02556203)90

References

bull In view of the superior anti-reste-

notic efficacy and no signal of higher

thrombotic risk of new-generation

DES it is recommended that patients

with AF undergoing PCI should be

treated with new generation DES

bull Choice of DAPT duration should not

be differentiated based on whether

the stent implanted at time of PCI is

a DES or bare-metal stent

bull Patients requiring oral anticoagula-

tion should not receive BRS

DES drug-eluting stent DAPT dual antiplatelet therapy BRS biovascularscaffold

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Third the Anti-Thrombotic Strategy after Trans-Aortic ValveImplantation for Aortic Stenosis (ATLANTIS n = 1509) trial is evalu-ating whether an anticoagulant-based strategy with apixaban 5 mg bidis superior to standard-of-care therapy in preventing death MIstroke systemic embolism intracardiac or bioprosthesis thrombusformation or life-threateningmajor bleeding complications at 1 yearfollow-up in patients successfully treated with a TAVI procedure TheATLANTIS trial will include two different populations patients withan indication for anticoagulation where standard of care is repre-sented by a VKA and patients for whom an antiplatelet regimen withaspirin plus clopidogrel is the first-choice antithrombotic treatmentRandomization is consequently stratified according to the need (orno need) for anticoagulation for clinical reasons other than TAVI it-self (NCT02664649)

Finally another study that aims at demonstrating the superiority ofa single anticoagulant vs the combination of an anticoagulation plusaspirin with respect to a net clinical benefit endpoint at 1 year (theAVATAR trial NCT02735902) has been announced (n = 170)

Among TAVI patients with AF but without CAD OAC is recom-mended in accordance with recommendations for AF alone1

Whether the addition of antiplatelet therapy to OAC is required inthis context remains to be determined The existing experience withpatients receiving biological aortic valve replacement suggests thatOAC alone may be sufficient to prevent thrombotic events79

Indeed OAC (essentially VKA) use in surgically-implanted biologicalaortic valves is generally recommended for only 3 months and can bestopped thereafter except where patients have other reasons forprolonged or life-long OAC

The POPular TAVI trial which is currently recruiting patients willprovide information regarding the safety and the net clinical benefitof a VKA alone vs the combination of clopidogrel plus a VKA inpatients undergoing TAVI who have an indication to permanentOAC91 With reference to the life-long use of a NOAC comparedwith VKA beyond the reported ATLANTIS trial the EdoxabanCompared to Standard Care after Heart Valve Replacement Using aCatheter in Patients with Atrial Fibrillation (ENVISAGE-TAVI AF)trial recently started recruiting a planned population of 1400 AFpatients undergoing TAVI The study will compare the two anticoag-ulant drugs (warfarin vs edoxaban) in terms of overall side effectsand major bleeding during 3 years follow-up (NCT02943785)

In summary TAVI patients taking OAC (eg for AF) and recentPCI should be treated similarly to patients receiving a stent withoutTAVI While awaiting results of controlled randomized trials patientsundergoing TAVI without concomitant need for OAC should receivean antiplatelet regimen consisting of lifelong aspirin monotherapy oraspirin and clopidogrel for 3ndash6 months followed by aspirin mono-therapy depending on bleeding risk and concomitant treated oruntreated coronary artery disease The use of prasugrel or ticagrelorin combination with aspirin or NOAC after TAVI has not been inves-tigated and cannot be recommended at this time

Mitral intervention

No study has addressed the optimal antithrombotic regimen afterpercutaneous edge-to-edge transcatheter mitral valve repair (egMitraClip system Abbott Abbott Park IL USA92) Pivotal studieshave mandated the use of aspirin for at least 6 months in combination

with clopidogrel for 1ndash3 months in patients without AF while patientswith AF are treated with OAC plus aspirin93

Transcatheter mitral valve implantation (TMVI) with a transcath-eter mitral valve prosthesis has been performed in patients with sur-gical degenerated bioprostheses [valve-in-valve (ViV)] or withrecurrent MR following mitral repair annuloplasty [valve-in-ring(ViR)]94 There is currently limited evidence that adding a single anti-platelet therapy or DAPT to OACs further decreases the risk ofsymptomatic or asymptomatic valve thrombosis

Left atrial appendage closure

The left atrial appendage (LAA) is implicated in approximately 90 ofstrokes in patients with AF95 Left atrial appendage occlusion eitherpercutaneous or surgical is a rapidly-emerging option for patientswho cannot take long-term OAC96 Of the percutaneous optionsthe WATCHMAN (Boston Scientific) device is so far the only testedLAA closure device in a randomized controlled fashion It is currentlythe only percutaneous device approved in both Europe and the US

In the PROTECT-AF trial patients were treated with warfarin andaspirin 81 mg for 45 days post-procedure then with aspirin and clopi-dogrel for 6 months and then with aspirin indefinitely97 In thePREVAIL study patients were on warfarin plus aspirin 81 mg for thefirst 45 days then on aspirin 325 mg plus clopidogrel until post-opera-tive month 6 (in the absence of any clot) then on aspirin 325 mgalone98 Thus PROTECT and PREVAIL did not enroll patients unableto take OACs but patients who were at least able to take warfarinfor 45 days post-procedure This contradicts the current suggestedindication to use a LAA closure device in patients with contraindica-tions against OACs Moreover the efficacy and safety of using aNOAC instead of warfarin was not assessed in these two majortrials

These trials have been subject to much debate99 with reports ofdevice related thrombus that can lead to thromboembolism100 Inthe absence of clinically relevant LAA leaks OAC can be discontin-ued and the patient treated with DAPT or a single antiplatelet ther-apy for at least 6 months after the procedure although somecardiologists continue single antiplatelet therapy long term Thereare also no data to suggest the optimal management of an AF patientwith left atrial appendage occlusion who requires a cardioversion Atransoesophageal echocardiogram (TOE) assessment for thrombusmay be performed and a shorten duration of anticoagulation similarto TOE-guided cardioversion protocol may be considered

AmplatzerThe data on Amplatzer Cardiac Plug (now Amulet) are largely basedon registry studies101102 The most recent study had 189 patientson either a VKA or NOAC immediately post-procedure101 In astudy of 52 Canadian patients receiving this device there was an only19 rate of stroke when antiplatelets alone were used post-procedure during a mean follow-up of 20 plusmn 5 months103

LariatThe LARIAT device (SentreHeart) ligates off the LAA via a combinedtrans-septal and epicardial approach It received FDA approval forsoft tissue closure but not specifically for LAA closure It has notbeen tested in a randomized controlled trial so efficacy data are

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derived from prospective registries104 Since the US FDA released asafety alarm communication in July 2015 due to reports of adversepatient outcomes the use of LARIAT in the US has dropped signifi-cantly (httpswwwfdagovMedicalDevicesSafetyAlertsandNoticesucm454501htm)

In summary LAA occlusion may be considered in selected AFpatients with absolute contraindications to any OAC Trial data sup-porting use of shorter duration TAT or even DAT in these patientsin general (as discussed above) as well as the recommendation forshort duration OAC after the procedure in patients treated withWatchman device makes the rationale for implanting these devicessolely for the reason that the AF patient requires PCI unclear

Assessing stroke and bleedingrisks

The CHA2DS2-VASc has been widely used worldwide for stroke riskstratification in AF105 even in patients with coronary artery diseasetreated with coronary stenting106107 Other less established risk fac-tors for stroke include unstable INR and low TTR in patients treatedwith a VKA previous bleed or anaemia alcohol excess and othermarkers for decreased therapy adherence chronic kidney diseaseelevated high-sensitivity troponin and elevated N-terminal pro-B-type natriuretic peptide2 Some have been incorporated into morerecent stroke scores proposed for AF such as the ATRIA(AnTicoagulation and Risk factors In Atrial fibrillation) QStroke andABC-stroke scores108ndash110 Biomarker-based stroke risk scores (egABC score) do not appear to confer long-term benefit over simpleclinical scores such as CHA2DS2-VASc111112 In addition stroke riskis not static and regular review and reassessment of risk is neededduring follow-up113114

In the CHA2DS2-VASc score the V criterion for lsquovascular diseasersquois defined as lsquoprevious MI peripheral artery disease or aortic plaquersquosince these are factors which are more validated to confer anexcess of stroke risk in patients with AF Patients with mild coronaryatheroma alone or simply a history of angina have not been defini-tively shown to have an excess of stroke risk if no other CHA2DS2-VASc risk factors are present (hence do not score a point for theV criterion) Patients with a CHA2DS2-VASc score of gt_1 for menor gt_2 for women are likely to benefit from stroke preventionwith specific treatment decisions for type and duration of associa-tions of antithrombotic agents based on the clinical setting and pa-tient profile (elective PCI or ACS risk factor for CAD progressionand coronary events risk of bleeding) possibly incorporating patientpreferences

Clinical risk scores for bleedingSeveral bleeding risk scores have been developed mainly in patientson VKAs These include HAS-BLED [hypertension abnormal renalliver function (1 point each) stroke bleeding history or predisposi-tion labile INR elderly (gt65 years) drugsalcohol concomitantly(1 point each)] ATRIA ORBIT (Outcomes Registry for BetterInformed Treatment of Atrial Fibrillation) and more recently theABC (age biomarkers clinical history) bleeding score which includesselected biomarkers115ndash118 While stroke and bleeding risks correlatewith each other the HAS-BLED score is a superior predictor of

bleeding risk compared with the CHADS2 [congestive heart failurehypertension age diabetes stroke (doubled)] or CHA2DS2-VAScscores119120

The simple HAS-BLED score has similar or a superior bleeding riskassessment to other proposed scores some of which are more com-plex121ndash123 This is particularly evident amongst VKA users given thatother scores (HEMORRH2AGES ATRIA ORBIT) do not considerquality of anticoagulation control ie labile INR as a bleedingrisk124125 In another trial cohort the ORBIT score demonstratedthe best discrimination and calibration when tested in the RE-LY(Randomized Evaluation of Long-term anticoagulant therapY withdabigatran etexilate) trial whereby all the scores demonstrated to avariable extent an interaction with bleeding risk associated with dabi-gatran or warfarin126 On the other hand the biomarker-based ABCbleeding risk score did not appear to confer long-term benefit over amore simple clinical score such as HAS-BLED112127 Similarly thePRECISE DAPT score has been developed to assess the out-of-hospital bleeding risk in patients in whom DAPT but not OAC is indi-cated however this score currently does not provide useful informa-tion on the additional bleeding risk in patients in whom both OACand DAPT are concomitantly indicated128

Of note the HAS-BLED ORBIT and ABC scores have also beenvalidated in patients on NOACs126129 The HAS-BLED score hasbeen validated in patients with CAD treated with coronary sten-ting130131 A high bleeding risk score should generally not result inwithholding OAC and is appropriately used to lsquoflag uprsquo patients athigh risk of bleeding (HAS-BLED score gt_3) for more regular reviewand earlier follow-up

Of importance modifiable bleeding risk factors (eg uncontrolledblood pressure concomitant antiplatelet or NSAID use alcohol ex-cess) should always be identified and corrected at every patient con-tact In addition bleeding risk is not static and regular review andreassessment of risk is needed during follow-up especially since anadverse change in (say) HAS-BLED score is associated with excessivebleeding risk particularly in the initial 3 months132

When managing patients with AF undergoing PCIstenting it is rec-ommended to concomitantly assess stroke bleeding and ischaemicevent risks (using validated tools such as the REACH Syntax andGRACE scores6133ndash135) A recent retrospective analysis confirmedthe value of the Syntax and GRACE scores for identifying higher risksof coronary events and mortality respectively in AF patients withcoronary stenting106

What is the practical application of formal bleeding risk assess-ment An approach based only on modifiable bleeding risk factorsalone is an inferior assessment compared with a formal bleeding riskscore119136137 A high (uncorrectable) bleeding risk may flag up thepatient for earlier review and follow-up (eg 4 weeks rather than 4ndash6 months) as well as lead to shortening of TAT with earlier switch toDAT in case of estimated low atherothrombotic risk as calculatedwith the Syntax or REACH score although prospective validation ismissing in such combination scenarios A similar clinical setting maylead to the decision to discontinue all antiplatelets and provide anti-coagulation as monotherapy earlier (eg after 6 months instead of1 year)26 In the small subset of AF patients undergoing PCI with ele-vated bleeding risk and a relatively low stroke risk (CHA2DS2-VAScof one in males or two in females) one option would be to treat withonly DAPT without OACs from the onset (although in ACTIVE-W

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there were numerically more MIs with aspirin plus clopidogrel com-pared with warfarin)138

The TIMI-AF score has recently been proposed in VKA-naivepatients with AF to assist in the prediction of a poor composite out-come and guide selection of anticoagulant therapy by identifying a dif-ferential clinical benefit with a NOAC or VKA139 This complexscore includes 11 items (including a history of MI) with a maximum in-teger score of 17 and needs to be more specifically validated in AFpatients with ACS andor undergoing percutaneous coronary orvalve interventions In a lsquoreal worldrsquo cohort of VKA-experienced AFpatients the TIMI-AF score was found to have limited usefulness inpredicting net clinical outcomes over a long-term period of follow-upand was not superior to CHA2DS2-VASc and HAS-BLED for identify-ing low-risk AF patients140 Another simple score the 2MACE [twopoints for Metabolic Syndrome and Age gt_75 one point for MIrevas-cularization Congestive heart failure (ejection fraction lt_40)thrombo-embolism (stroketransient ischaemic attack)] score hasalso been proposed for the prediction of MACE but has not beenvalidated in AF patients undergoing PCI141142

Optimizing management

Table 3 summarizes the key points outlined in major European andAmerican guidelines in patients undergoing percutaneous coronaryinterventions when on oral anticoagulation

From the OAC perspective the main management aspects pertainto the introduction of the NOACs The latter drugs have changedthe landscape of stroke prevention management amongst patientswith AF although some regional differences are evident145

Table 4 provides a summary of the antithrombotic managementdifferences between a VKA and NOAC in relation to management ofAF patients presenting with an ACS andor undergoing PCIstenting

Elective percutaneous cardiovascularintervention for stable coronary arterydiseaseSince the publication of the 2014 consensus document several stud-ies (mostly observational) have been published8ndash3234ndash3739146147

As opposed to some studies where only patients with ACS havebeen included none reported exclusively on AF patients undergoingPCI in the context of stable CAD The proportion of patientswith stable CAD included in the various studies was in the range of20ndash08ndash3234ndash3739146147

Only extrapolation from the overall data can therefore be madewhen attempting to address the main issues in the management of AFpatients undergoing PCI in the context of stable CAD namely peri-procedural management of OAC especially in the current era whenboth VKA and NOAC anticoagulants are available and combinationand duration of antithrombotic therapy during the medium to long-term after the procedure

Periprocedural management

In patients receiving a VKA an uninterrupted strategy is supported byvarious studies In a meta-analysis of uninterrupted when comparedwith interrupted strategy58 uninterrupted OAC was found to be atleast as safe as interrupted OAC and seemed to be much safer than

interrupted OAC with bridging anticoagulation in patients undergo-ing coronary angiography with or without PCI

In the WOEST study148 where 573 patients on OAC with VKAfor various indications (mostly AF) underwent PCI with stable CADin approximately 70 the procedure was carried out without OACinterruption in 241 (43) and with OAC interruption plus low-mo-lecular weight heparin (LMWH) bridging in the remaining 322 (57)In most cases the vascular approach was femoral and comparable inthe two groups At 30 days as well as at 1 year follow-up the occur-rence of bleeding events was comparable in both groups (HR 08395 CI 050ndash137 P = 046 and HR 101 95 CI 071ndash144 P = 095respectively)148 Also comparable was the occurrence of MACCEincluding death MI stroke target vessel revascularization and stentthrombosis at both 30 days and 1 year (HR 048 95 CI 015ndash151P = 021 and HR 072 95 CI 046ndash114 P = 016 respectively)148

In the AFCAS registry where 663 out of 929 patients with AF un-dergoing PCI (for stable CAD in approximately 50) 498 (75) haduninterrupted periprocedural OAC whereas the remaining 165(25) had OAC interruption and LMWH bridging149 At 3 monthsboth unadjusted major bleeding and MACCE rates were significantlymore frequent in the LMWH-bridging group whereas at 12 monthsthe difference remained statistically significant only for MACCE149

After propensity score matching and subsequent comparison of 152patients in whom also the frequency of femoral access was similarmajor bleeding was more frequent in the LMWH-bridging group atboth 3 and 12 months whereas MACCE rates were comparable149

The preferential role of radial access in patients on OAC with VKAundergoing PCI is corroborated by a retrospective single-centreanalysis of 97 patients undergoing PCI (proportion of stable CADnot reported) with INRs gt20 in whom total and major BARC bleed-ing and need for transfusions was significantly lower with radial whencompared with femoral approach150

Limited data are available for AF patients undergoing PCI while onNOAC In the phase IIa multicentre D-fine clinical trial 50 patientsundergoing elective PCI were randomized to either pre-proceduraldabigatran 110 or 150 mg bid or standard intra-procedural UFH151

Following PCI dabigatran appeared to provide insufficient anticoagu-lation as shown by significantly higher values compared with UFH ofprothrombin fragment 1thorn 2 and thrombin-antithrombin complex-es152 Clinical outcomes tended to be higher in the dabigatran groupwhere 5 out of 40 (125) required bail-out anticoagulation whencompared with 1 out of 10 (10) in the standard UFH group151

No significant bleeding was observed in either group151

In a phase IIa multicentre trial (X-plorer) 108 patients undergoingelective PCI and on stable dual antiplatelet therapy of aspirin and clo-pidogrel were randomized to a single dose of either rivaroxaban10 mg rivaroxaban 20 mg rivaroxaban 10 mg plus intravenous bolusof UFH or standard UFH152 Patients with an indication for OACwere excluded Following PCI in all groups receiving rivaroxaban co-agulation was effectively suppressed comparably to standard UFH asshown by the low plasma levels of the fragment 1thorn 2 and thrombin-antithrombin complex152 No patients in the three rivaroxaban armsrequired bail-out antithrombotic medication andor had clinical signsof catheter-related thrombosis152 No significant bleeding was ob-served in either group up to 30 days after PCI152

Because of the inconsistency of the results reported with the twodifferent NOACs (dabigatran and rivaroxaban) performing elective

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PCI in patients with stable CAD on ongoing uninterrupted NOACmonotherapy is currently not recommended Also uncertainty onthe true level of anticoagulation with NOAC raises uncertainty whenthe treatment of a thrombotic complication is needed eg adminis-tration of glycoprotein IIbIIIa (GPIIbIIIa) inhibitors153 or the optimaluse of additional UFH

Whereas intra-procedural anticoagulation with UFH should becarried out as per usual practice in AF patients on NOAC uncer-tainty exists on whether additional UFH should be given to patientson OAC with VKA undergoing PCI while the INR is gt20 In a casendashcontrol study on 336 patients undergoing transradial coronary angi-ography either on therapeutic warfarin or standard intra-proceduralUFH the incidence of both early (24-h) and late (30-day) radial arteryocclusion was significantly higher in the ongoing warfarin group154

thereby supporting the addition of UFH also in VKA patients Giventhat doses as low as 30ndash50 Ukg have been shown effective in pre-venting ischaemic complications related to PCI155 they should bepreferred with the aim of limiting the risk of bleeding When coro-nary angiography is performed through the femoral approach (low-dose) UFH should likely be added only if PCI is carried out given theuncertainty on the degree of protection provided by ongoing thera-peutic VKA156

Whether bivalirudin which in both stable and ACS patients hasbeen shown to be associated with a significantly lower rate of bleed-ing than UFH plus glycoprotein (GPI)157 may be a preferable optionfor intra-procedural anticoagulation on ongoing effective VKA is un-certain Limited observational data suggest that bivalirudin may in-deed be preferred given that the 30-day occurrence of majorbleeding and MACCE was shown to be lower in 51 patients receivingbivalirudin (stable CAD in 47) when compared with 87 treatedwith UFH plus GPI (stable CAD in 15) who were identified out of1104 on warfarin undergoing PCI in two study protocols158

While there is a general agreement on the need for at least initialTAT of OAC plus DAPT of aspirin and clopidogrel in most AFpatients undergoing PCI the optimal timing and schedule for antipla-telet agents administration is not established In patients not on OAC

and stable aspirin therapy clopidogrel may be administered eitherprior to or during PCI with no apparent differences in outcomes withthe two strategies159 Given that TAT is associated with an increasedrisk of bleeding it may be considered to withhold the additional anti-platelet agent until indication for PCI arises from diagnostic coronaryangiography

The time required to reaching effective platelet inhibition with oralloading of clopidogrel is approximately 2 to 6ndash8 h depending onwhether a 600 or 300 mg dose respectively is given160 as opposedto either intravenous or oral aspirin which has a nearly immediateantiplatelet effect161 When carried out pre-treatment with both as-pirin and clopidogrel should preferably include loading with 300 mggiven that the slower and less intense platelet inhibition comparedwith 600 mg162 may reduce the initial risk of bleeding in patients naiveto antiplatelet therapy and on ongoing OAC

No additional data are available on GPI use in AF patients treatedwith OAC undergoing PCI As for non-OAC patients with stableCAD indication for GPI remains essentially limited to bail-out situa-tions where however further care is advised given the previouslyreported substantial risk of major bleeding in the absence of a signifi-cant benefit on MACCE153 When abciximab is used bolus only ei-ther intracoronary or intravenous may be considered because ofpossible superior safety compared with conventional intravenous bo-lus plus infusion strategy163 Use of GPI as per standard practice canbe considered for patients on NOAC when timely discontinuationbefore PCI has been carried out

Acute managementNo randomized trials have specifically studied periprocedural man-agement in anticoagulated patients developing an ACS and undergo-ing acute angiography with or without PCI The following suggestionsare based on observational studies and expert opinion and are in ac-cordance with recent ESC guidelines5164165 All AF patients takingOAC developing an ACS should receive aspirin immediately [150ndash300 mg oral loading dose or 75ndash150 mg iv (intravenous)]164 To re-duce the risk of bleeding one option is to postpone the

Table 3 Summary of main recommendations in recent guidelines

ESC myocardial

revascularization

2017143

AF 20162

ACCAHA

2016 combined

OACAPT144

ESC 2017

update5

Use of periprocedural aspirin and clopidogrel thornthornPreferred use of DES thornthorn thornthornRecommendations according to the type of platform (DES vs BMS) na thornthorn na

Use of ticagrelor or prasugrel Use of specific score for ischaemic or bleeding risks thornthorn na na na

DAPT as an alternative to TAT in CHA2DS2-VASc score lt_1 thornthorn na na na

DAT as an alternative to initial TAT thorn thorn na thornthorn1ndash6 months as the default strategy in ACS patients thornthorn thornthorn thornthorn thornthornUse of NOAC thornthorn thornthorn thornthorn thornthornStopping aspirin rather than clopidogrel thorn thorn thornthorn thornStopping all antiplatelet therapy after 1 year na thornthorn na thornthorn

thornthorn recommended thorn may be considered not recommended by the relevant guideline ACS acute coronary syndrome BMS bare-metal stent DAT dual therapy DESdrug-eluting stent na box means not stated NOAC non-vitamin K antagonist oral anticoagulant TAT triple therapy

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bullBe

(12ndash

ndash48

(30ndash

(70ndash

limite

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0ndash2

ndash70

ndash30

65ndash7

ithits

20ndash

65ndash7

to3ndash

ndash100

limite

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20ndash

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administration of P2Y12 inhibitors to the time of PCI when the anat-omy is known165

Oral anticoagulation is a relative contraindication for fibrinolysisWhen anticoagulated patients present with a STEMI they should betriaged for primary PCI regardless of the anticipated time to PCI-mediated reperfusion164 Primary PCI via a radial approach is stronglyrecommended166 and clopidogrel is the P2Y12 inhibitor of choice(600 mg loading dose given at the time of primary PCI)164

The more potent P2Y12 inhibitors prasugrel and ticagrelor are gen-erally not routinely recommended in anticoagulated patients due totheir increased bleeding risk in combination with aspirin6165167

Anticoagulated patients undergoing primary PCI should receive addi-tional low-dose parenteral anticoagulation regardless of the timing ofthe last dose of OAC (VKA or NOAC) (eg enoxaparin 05 mgkg ivor UFH 60 IUkg)165

In NSTE-ACS patients undergoing an immediate invasive strategy(ie lt2 h from symptom onset) periprocedural treatment should beas in STEMI patients If invasive treatment is delayed it is still sug-gested to perform PCI without interruption or discontinuation ofVKAs or possibly NOACs58165 As discussed above an uninter-rupted strategy was not associated with an increase in bleeding ormajor cardiovascular events compared with bridging therapy58168 Inpatients on VKAs it is suggested either not to administer additionalintraprocedural UFH if INR value is gt25 or to consider a lower UFHdose regime165 In patients on NOACs additional intraprocedurallow-dose parenteral anticoagulation (eg enoxaparin 05 mgkg iv orUFH 60 IUkg) should be added irrespective of the time of the last ad-ministration of NOAC165 GPIs should be avoided unless for bail-out

situations The new bioabsorbable vascular scaffolds should not beused in patients on OAC due to their higher thrombotic risk andneed for a longer DAPT duration169

Post-procedural and post-discharge therapy

As regards the anti-thrombotic treatment to be prescribed atdischarge most of the additional evidence published since 2014reports that TAT of OAC with either VKA or NOAC is consis-tently associated with an increased risk of major or total bleedingcompared with other regimens with more heterogeneous effect onMACCE8ndash3234ndash3739146147 The several limitations of observationalstudies including lack of randomization small size insufficient infor-mation on treatment adherence quality of OAC and limited absolutenumber of events preclude definitive conclusions especially regard-ing efficacy

For most patients TAT in the form of OAC aspirin and clopidog-rel should be considered for 1ndash6 months after an ACS2164165 Theoptimal duration of such TAT depends on the patientrsquos ischaemic andbleeding risks Non-vitamin K antagonist oral anticoagulants as part ofTAT or DAT are generally safer than VKA use with respect to bleed-ing risk and is the preferred option in the absence of contraindica-tions to these drugs

Three randomized trials (WOEST PIONEER AF PCI and RE-DUAL PCI)3940148 showed that double therapy with a P2Y12 inhibi-tor and either VKA (WOEST) or a NOAC (PIONEER REDUALPCI) was safer with respect to bleeding than TAT However none ofthese studies were sufficiently powered for efficacy and the popula-tions studied were a mixture of stable CAD and ACS patients Of

AF patients undergoing PCI

VKA NOAC

Any clinical setting

At the time ofprocedure

H heparin(s) (either UFH or enoxaparin)

when NOAC has been timely interrupted when NOAC has not been timely interrupted^ at reduced dose bivalirudin may be considered instead

O A C H^ H^ H^A C O A C

ElectiveNSTE-ACS STEMINSTE-ACS

Figure 1 Intra-procedural antithrombotic strategies in AF patients undergoing PCI in relation to VKA or NOAC use For NOACs in electiveNSTE-ACS interruption (12ndash24 h in advance based on renal function and agent) is preferred A aspirin AF atrial fibrillation C clopidogrel H hepa-rin NOAC non-vitamin K antagonist oral anticoagulant NSTE-ACS non-ST-elevation acute coronary syndrome O oral anticoagulation PCI per-cutaneous coronary intervention STEMI ST-elevation myocardial infarction VKA vitamin K antagonist

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note a signal of increased harm in the risk of stroke was apparent inthe very low dose ie 25 mg bid rivaroxaban arm compared withconventional TAT(39) In the RE-DUAL PCI trial a numerical trendfor more thrombotic endpoints was also seen with the dabigatran110 mg bid arm3940 Until more data are available TAT is still the rec-ommended as the initial treatment for the first month after PCI or anACS in patients with a high ischaemic risk and a low bleeding risk5

Trials with apixaban and edoxaban are ongoing Because full-doseapixaban 5 mg bid and edoxaban 60 mg od were associated with sig-nificantly less major bleeding than warfarin in the ARISTOTLE(Apixaban for Reduction of Stroke and Other ThromboembolicEvents in Atrial Fibrillation)170 and ENGAGE AF-TIMI 48171 trials forstroke prevention in non-valvular AF these doses should generallybe selected for TAT Whereas safety of reduced-dose apixaban25 mg bid and edoxaban 30 mg bid is likely higher true efficacy instroke prevention is unknown when these doses are used in the ab-sence of factors qualifying patients for dose reduction and shouldtherefore generally not be used even when DAPT of aspirin and clo-pidogrel is given in conjunction

In patients with a low risk of bleeding TAT may be extended lon-ger for to 3ndash6 months depending on the clinical scenario After this

period of TAT OAC plus aspirin or (preferably) clopidogrel shouldbe considered up to 12 months after PCI After 1 year it is reasonableto maintain OAC alone25

In cases of high bleeding risk DAT (OAC plus aspirin or preferablyclopidogrel) may be considered from the time of discharge and con-tinued for 1 year followed thereafter by OAC alone25 WhenNOACs are used in general dose reduction below the approveddoses for stroke prevention is not recommended The dose intensityof VKA should be carefully monitored with an INR in the lower partof the recommended range and to ensure good quality anticoagula-tion control as reflected by high TTR (eg gt65ndash70) Gastric protec-tion with a proton pump inhibitor (PPI) is recommended in patientson triple therapy and in high bleeding risk patients on doubletherapy165

As regards the optimal duration of TAT especially with the aim ofreducing the risk of bleeding both the prospective randomizedISAR-TRIPLE trial147 and the observational data by Koskinas et al20

have provided additional information In the ISAR-TRIPLE trial147

614 patients receiving concomitant aspirin and VKA after PCI (forstable CAD in approximately 65) with implantation of new-generation DES in about 80 of cases were randomized to either 6-

AF Patients presenting with Elective PCI or ACS undergoing PCI1

Concerns aboutthrombotic risk2

prevailing

Dual Therapy with OAC plusP2Y12 inhibitor up to 12 mo

OAC alone

Time fromtreatmentinitiation

Beyond12mo

1 Periprocedural administration of aspirin and clopidogrel during PCI is recommended irrespective of thetreatment strategy as dual therapy potent P2Y12 inhibitors (ticagrelor) may be combined with dabigatran

2 High atherothrombotic risk (For Elective PCI use SYNTAX score for ACS GRACE score gt140 stenting of the leftmain proximal LAD proximal bifurcation recurrent MIs stent thrombosis etc) and low bleeding risk

3 Bleeding risk can be estimated using the HAS-BLED score correct modifiable bleeding risk factors

(Patient very high bleeding risk)

1 mo Triple Therapy

Triple Therapyup to 6 mo

O Oral anticoagulant withVKA (TTRgt70) or NOAC

Aspirin

Clopidogrel

Concerns about high bleeding risk3

prevailing

1 mo Triple Therapy

Figure 2 Management algorithm for AF patients presenting with elective PCI or ACS undergoing PCI

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week or 6-month clopidogrel therapy At 9-month follow-up thecomposite in incidence of death MI definite stent thrombosis or ma-jor bleeding was comparable in the two groups147 In the analysis byKoskinas et al20 of the prospective Bern PCI registry out of the 568patients with indication for VKA and discharged on TAT 245 (43)were prescribed 1-month duration of treatment whereas the remain-ing 323 (57) were prescribed 6-month after PCI with implantationof new-generation DES in about 60 of cases20 At 1 year the pri-mary composite endpoint of cardiac death MI stroke definite stentthrombosis or major bleeding was comparable in the two groups20

In the current era of new-generation less thrombogenic DES itappears therefore that duration of TAT in OAC patients may be lim-ited to 1ndash3 months only No data were available on the quality ofOAC nor on the recommended INR range (commonly 20ndash25) butobservational data suggest that freedom from major bleeding eventsmay indeed be inversely related to TTR values8

Additional evidence on the regimen to adopt or prolong after theinitial course of TAT has been concluded is not available As per ac-cepted recommendations withdrawal of one of the two antiplateletagents either aspirin (preferably) or clopidogrel should be per-formed and combination of ongoing OAC (either VKA or NOAC)should be continued up to 1 year If reduced dose rivaroxaban 15 mgod was ongoing full dose 20 mg od could be started when one anti-platelet agent is withdrawn The decision whether or not to increasethe dose of dabigatran from 110 to 150 mg bid should be left at thediscretion of the attending care provider based on the patientrsquos over-all risk of bleeding and stroke

Post hoc analyses of the stroke prevention trials did not suggest re-duced efficacy or increased harm when NOAC plus antiplatelet ther-apy was compared with VKA plus antiplatelet therapy

Atrial fibrillation occurring early afterpercutaneous cardiovascularintervention in acute coronary syndromepatientsApproximately 10 of patients hospitalized for ACS and generallyundergoing PCI plus stenting develop AF in the early phase172

Although it is presently unclear whether new onset AF associatedwith ACS has the same risk as a prior history of paroxysmal AF173

OAC should be generally prescribed according to the individual riskof stroke usually in combination at least for some time with antipla-telet agents Initiation of warfarin in OAC-naive patients as generallyare those developing AF in the context of an ACS is associated withan increase risk of bleeding which may result in the withdrawal ofantithrombotic agents therefore increasing the risk of thromboem-bolic events174 In the absence of established factors requiring dosereduction the appropriate dose of NOAC should be given as dis-cussed above175

Long-term management

After 1 year of combined OAC and (dual and single) antiplatelet ther-apy has been completed OAC monotherapy (either VKA orNOAC) should be continued long term Based on historical datawith warfarin176 the efficacy of OAC monotherapy in secondary pre-vention after a coronary event appears at least comparable to stan-dard aspirin VKA monotherapy has been associated with significantly

less major bleeding compared with combined VKA and antiplatelettherapy with no difference in the risk of cardiovascular death MI ornon-haemorrhagic stroke at 2 years177 Extrapolation of the VKAresults has been made for NOAC

Given the lack of specific data combined OAC and single antiplate-let agent either aspirin or clopidogrel may be considered long-termonly in highly selected cases with a very increased ongoing ischaemicrisk when clinical andor anatomical circumstances indicate a highrisk of thrombosis andor major cardiovascular events if stent throm-bosis occur

Consensus statements for themanagement of atrial fibrillationpatients presenting with anpercutaneous cardiovascularintervention andor undergoingpercutaneous cardiovascularinterventionstenting

In general the period of TAT should be as short as possible followedby OAC plus a single antiplatelet agent (clopidogrel 75 mg od or al-ternatively aspirin 75ndash100 mg od) The duration of TAT is dependenton a number of considerations acute vs elective procedures bleed-ing risk (as assessed by the HAS-BLED score) type of stent (with apreference for new-generation DES or BMS) Suboptimal stent place-ment might also increase the risk for ischaemic events and should beavoided in selected cases by use of intracoronary imaging techniques

In case we refer to OAC this can be with well-controlled ad-justed-dose VKA (with TTR gt70) or with a NOAC

General management considerations

In AF patients stroke risk must be

assessed using the CHA2DS2-

VASc score and bleeding risk

should be assessed using the

HAS-BLED scorebull Stroke and bleeding risk stratifi-

cation is a dynamic process and

must be performed at regular

intervalsbull Every effort should be made to

address modifiable bleeding risk

factors at every patient contactbull Established bleeding scores eg

HAS-BLED should be used to

draw attention to modifiable

bleeding risk factors and to iden-

tify the patients for earlier review

and followup

106107113122

130136137

Continued

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An initial period of triple therapy

should be used in most AF

patients undergoing PCI depend-

ing on presentation (ACS vs elec-

tive) stroke vs bleeding risk

procedural considerations (eg

disease severity) etcbull Dual therapy with OAC plus one

P2Y12 inhibitor (usually clopidog-

rel) may be considered in

patients who are predisposed to

excessive bleeding risk and have

low thrombotic risk

In anticoagulated patients pretreat-

ment with antiplatelet therapy is

appropriate if PCI plannedbull Clopidogrel is the P2Y12 inhibitor

of choice in anticoagulated

patients prasugrel and ticagrelor

should be avoided in patients also

receiving aspirin due to their

higher bleeding risk if used in

combination as part of a TAT

regimen

bull In anticoagulated patients post-

pone pretreatment with P2Y12

inhibitors if the coronary anat-

omy is not known

NOACs as part of TAT or DAT are

safer than VKA (eg Warfarin)

with respect to bleeding risk and

is the preferred option in the ab-

sence of contraindications to use

of these drugsbull AF patients with CHA2DS2-VASc

score gt_2 treated with a NOAC

should continue their NOAC in-

definitely with addition of anti-

platelets for up to 12 months

after PCIACS

DAT with rivaroxaban or dabigatran

and a P2Y12 inhibitor is associated

with a lower risk of bleeding than

TAT with warfarinbull None have been sufficiently eval-

uated with respect to efficacy

When dabigatran is used as part of

DAT the standard doses of 150

mg bid should be used to reduce

the risk of ischaemic events

Continued

bull As per prescribing label dabiga-

tran 110 mg bid can be consid-

ered in elderly patients

concomitant when PgP inhibitors

(eg verapamil) are used and in

patients with high bleeding riskbull Both dabigatran 150 mg or 110

mg bid have been shown to be

non-inferior (and in the case of

150 mg bid superior) to warfarin

for stroke prevention in AF

When rivaroxaban is used as part of

DAT reduced dose 15 mg od

should be consideredbull The efficacy with respect to

stroke prevention of this reduced

dose in this population has not

been sufficiently evaluated

When apixaban or edoxaban are

used as part of TAT or DAT the

standard dose (5 mg bid and 60

mg od respectively unless label-

guided dose reduction is indi-

cated) should be selected pending

results of ongoing trials

Expert consensus

When VKA is given in combination

with clopidogrel andor low-dose

aspirin the dose intensity of VKA

should be carefully regulated

with a target INR range of 20ndash

25bull Good quality anticoagulation is

recommended with a high time

in therapeutic range (TTR gt65ndash

70) aimed for

In patients on VKA undergoing cor-

onary angiography andor PCI an

uninterrupted VKA strategy is at

least as safe as interrupted VKA

and seems to be much safer than

interrupted VKA with bridging

anticoagulation

Patients with AF and stable vascular

disease (arbitrarily defined as be-

ing free from any acute ischaemic

event or repeat revascularisation

for gt1 year) should be managed

with OAC alone

Continued

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Radial access should be considered

as the default approach for coro-

nary angiographyintervention to

minimize the risk of access-re-

lated bleeding depending on op-

erator expertise and preference

Gastric protection with PPIs should

be considered in all patients with

OAC plus antiplatelet therapy

Long-term antithrombotic therapy

(beyond 12 months) is recom-

mended with OAC in all patientsbull Combination OAC plus single

antiplatelet therapy (ie aspirin)

may sometimes be continued in

very selected cases eg stenting

of the left main proximal bifurca-

tion recurrent MIs etc

Elective or stable CAD

For NOAC-treated patients under-

going elective PCI timed cessa-

tion (eg gt12ndash48 h) before

intervention may be considered

depending on the agent and renal

function (see text) and use of

standard local anticoagulation

practices periprocedurallybull Early after PCI such as the same

evening or the next morning

NOAC therapy should be

restarted

In patients with stable CAD and AF

undergoing PCI at low bleeding

risk (HAS-BLED lt_2) TAT (OAC

aspirin 75ndash100 mg daily clopidog-

rel 75 mg daily) should be given

for a minimum of 4 weeks (and

no longer than 6 months) after

PCI following which DAT with

OAC and clopidogrel 75 mgday

(or alternatively aspirin 75ndash100

mgday) should be continued for

up to 6ndash12 months

undergoing PCI at high bleeding

risk (HAS-BLED gt_3) TAT (OAC

rel 75 mg daily) or DAT consist-

ing of OAC and clopidogrel 75

mgday should be given for 1

Continued

month after PCI following which

DAT with OAC and clopidogrel

75 mgday (or alternatively aspi-

rin 75ndash100 mgday) should be

continued for up to 6 months be-

yond which patients would be

managed on OAC alonebull In patients at very high bleeding

risk (eg recent bleeding event)

aspirin may be omitted and DAT

with a NOAC and clopidogrel 75

mgday continued for 3ndash6

months beyond which patients

would be managed on OAC

with OAC (beyond 12 months) is

recommended in all patientsbull Combination OAC plus single

may be considered in only very

selected cases with an increased

ongoing ischaemic risk

When the procedures require inter-

ruption of OAC for longer than

48 h in high-risk patients (ie

TAVI or other non-PCI proce-

dures at high bleeding risk) enox-

aparin may be administered

subcutaneously although the effi-

cacy of this strategy is uncertainbull Bridging is often considered in

patients with mechanical heart

valves recent strokevenous

thromboembolism (lt3 months)bull Pharmacodynamic data suggest

that enoxaparin might be a better

option than unfractionated hepa-

rin because of the more predict-

able and stable level of

anticoagulationbull Such lsquobridgingrsquo therapies may be

associated with an excess bleed-

ing risk possibly due to dual

modes of anticoagulation in the

overlap periodsbull When NOACs are used timing

of any bridging therapy should be

tailored based on renal function

and the pharmacokinetics of the

specific NOAC

Expert consensus

Continued

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NSTE-ACS including unstable angina and NSTEMI

In patients on OAC developing a

NSTE-ACS aspirin loading should

be as in STEMI and clopidogrel is

again the P2Y12 inhibitor of

choicebull As clopidogrel takes considerable

time to achieve its maximal anti-

platelet effect in unstable

patients clopidogrel without as-

pirin cannot be recommended in

the acute or periprocedural

phasebull Pretreatment with P2Y12 recep-

tor antagonists may be withheld

until the time of coronary angiog-

raphy in case of an early invasive

strategy within 24 hbull The use of ticagrelor or prasugrel

in combination with OAC may

only be considered under certain

circumstances (eg definite stent

thrombosis while on clopidogrel

aspirin and OAC)

Administer unfractionated heparin

or bivalirudin only as bailout (but

avoiding GPIIbIIIa inhibitors) or if

INRlt_2 in a patient on VKA bal-

ancing the acute need for addi-

tional antithrombotic therapy

with the excess bleeding risk and

the lsquothrombus burdenrsquobull Glycoprotein IIbIIIa inhibitors

should be avoided unless for bail-

out situations due to the in-

creased risk of bleeding associ-

ated with their use

Expert consensus

TAT is still the recommended initial

treatment for the first month af-

ter PCI or an ACS in AF patients

with a high ischemic risk and a

low bleeding risk

An early invasive strategy (within 24

h) should be preferred among AF

patients with moderate to high-

risk NSTE-ACS in order to expe-

dite treatment allocation (medical

vs PCI vs coronary artery bypass

grafting) and to determine the op-

timal antithrombotic regimen

Continued

In AF patients with ACS at low risk

of bleeding (HAS-BLED 0ndash2) the

initial use of TAT (OAC aspirin

and clopidogrel) should be con-

sidered for 3ndash6 months following

PCI irrespective of stent type this

should be followed by long term

DAT (up to 12 months) with

OAC and clopidogrel 75mgday

mgday)

In patients with ACS and AF at high

risk of bleeding (HAS-BLED gt_3)

the initial use of TAT (OAC aspi-

rin and clopidogrel) should be

considered for 4 weeks following

mgday)bull In patients at very high bleeding

aspirin may be omitted and dual

therapy with OAC and clopidog-

rel 75 mgday continued for 3ndash6

would be managed with OAC

(beyond 12 months) with OAC

whether with VKA or NOAC is

may be considered in very se-

lected cases eg extensive multi-

vessel CAD last remaining patent

coronary artery stenting of the

left main stem or a proximal bi-

furcation recurrent MIs etc

Primary PCI

When anticoagulated patients pre-

sent with a STEMI they should be

triaged for primary PCI regardless

of the anticipated time to PCI-me-

diated reperfusion

14ndash6

Continued

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Areas for future research

Dual antithrombotic therapy by omittingaspirin in secondary prevention afteracute coronary syndrome in patientswith atrial fibrillationAlthough both the PIONEER-AF179180 and RE-DUAL PCI40 trialshave shown a benefit of DAT (ie a NOAC in combination with clo-pidogrel) over TAT some questions still remain and need to be an-swered Both studies miss a DAT comparator with VKA plusClopidogrel Moreover 15 mg rivaroxaban in combination with clo-pidogrel does not reflect current guidelines that the NOAC shouldbe used in the lowest dose that has been tested for strokereduction5

Finally the use of potent P2Y12-inhibitors (ticagrelor or prasugrel)in combination with a NOAC in this indication is still not sufficientlyproven given that only 12 of patients in RE-DUAL PCI and a minor-ity in PIONEER-AF had these drugs A particular patient group forfurther research with these newer agents includes those with high onclopidogrel platelet reactivity especially in patients with a high preva-lence of comorbidity181182 Such high on treatment platelet reactivitymay have implications for prognosis and optimal managementremains uncertain183

New anticoagulants and new antiplateletagents on the horizonThe search for the lsquoholy grailrsquo of anticoagulation an agent that com-bines optimal efficacy with minimal bleeding diathesis continuesAlso novel antiplatelet drugs that selectively inhibit arterial thrombo-sis without interfering with normal haemostasis may yet occur Newantiplatelet drugs interfering with the interaction of von Willebrandfactor (VWF) with glycoprotein (GP) Iba and directed against GPVIGPIIbIIIa (integrin aIIbb3) the thrombin receptor PAR-1 and theADP receptor P2Y12 are on the horizon184

The development of new anticoagulant drugs is also rapidlyexpanding targeting other factors in the coagulation cascade such asFactor XI and XII185186 Factor XI has emerged as a particularlypromising target for new anticoagulants that may be even safer thanthe NOACs given the reduced thrombosis in factor XI-deficientmice and that congenital factor XI deficiency is associated with only amild bleeding diathesis187 A recent Phase II trial showed that whencompared with enoxaparin factor XI inhibition by an antisense anti-body reduced venous thromboembolism without increasing bleedingafter elective knee arthroplasty188 Whether these new drugs can betranslated to thromboprophylaxis for AF patients in the ACS or PCIsetting requires further investigation

Supplementary material

Supplementary material is available at Europace online

Conflict of interest See Supplementary material online

In the setting of STEMI radial access

for primary PCI is the best option

when feasible to avoid proce-

dural bleeding depending on op-

14ndash6

In patients with STEMI and AF at

low risk of bleeding (HAS-BLED

0ndash2) the initial use of TAT (OAC

aspirin and clopidogrel) should be

considered for 6 months follow-

ing PCI irrespective of stent type

this should be followed by long

term DAT (up to 12 months)

with OAC and clopidogrel 75 mg

day (or alternatively aspirin 75ndash

100 mgday)

high risk of bleeding (HAS-BLED

gt_3) the initial use of TAT (OAC

aspirin and clopidogrel) should

be considered for 4 weeks follow-

100 mgday)bull In patients at very high bleeding

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References1 Lip GY Windecker S Huber K Kirchhof P Marin F Ten Berg JM et al

Management of antithrombotic therapy in atrial fibrillation patients presentingwith acute coronary syndrome andor undergoing percutaneous coronary orvalve interventions a joint consensus document of the European Society ofCardiology Working Group on Thrombosis European Heart RhythmAssociation (EHRA) European Association of Percutaneous CardiovascularInterventions (EAPCI) and European Association of Acute Cardiac Care(ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific HeartRhythm Society (APHRS) Eur Heart J 2014353155ndash79

2 Kirchhof P Benussi S Kotecha D Ahlsson A Atar D Casadei B 2016 ESCGuidelines for the management of atrial fibrillation developed in collaborationwith EACTS Europace 2016181609ndash78

3 Chiang CE Wang TD Lin TH Yeh HI Liu PY Cheng HM The 2017 FocusedUpdate of the Guidelines of the Taiwan Society of Cardiology (TSOC) and theTaiwan Hypertension Society (THS) for the Management of Hypertension ActaCardiol Sin 201733213ndash25

4 Ibanez B James S Agewall S Antunes MJ Bucciarelli-Ducci C Bueno H 2017ESC Guidelines for the management of acute myocardial infarction in patientspresenting with ST-segment elevation the Task Force for the management ofacute myocardial infarction in patients presenting with ST-segment elevation ofthe European Society of Cardiology (ESC) Eur Heart J 201839119ndash77

5 Valgimigli M Bueno H Byrne RA Collet JP Costa F Jeppsson A et al 2017 ESCfocused update on dual antiplatelet therapy in coronary artery disease devel-oped in collaboration with EACTS the Task Force for dual antiplatelet therapyin coronary artery disease of the European Society of Cardiology (ESC) and ofthe European Association for Cardio-Thoracic Surgery (EACTS) Eur Heart J201839213ndash60

6 Steffel J Verhamme P Potpara TS Albaladejo P Antz M Desteghe L et al The2018 European Heart Rhythm Association Practical Guide on the use of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation executivesummary Europace 2018 doi101093europaceeuy054 [Epub ahead of print]

7 Lip GYH The ABC pathway an integrated approach to improve AF manage-ment Nat Rev Cardiol 201714627ndash8

8 Proietti M Airaksinen KEJ Rubboli A Schlitt A Kiviniemi T Karjalainen PP et alTime in therapeutic range and major adverse outcomes in atrial fibrillationpatients undergoing percutaneous coronary intervention the Atrial FibrillationUndergoing Coronary Artery Stenting (AFCAS) registry Am Heart J 201719086ndash93

9 Choi HI Ahn JM Kang SH Lee PH Kang SJ Lee SW et al Prevalencemanagement and long-term (6-year) outcomes of atrial fibrillation amongpatients receiving drug-eluting coronary stents JACC Cardiovasc Interv 2017101075ndash85

10 Rubboli A Saia F Sciahbasi A Leone AM Palmieri C Bacchi-Reggiani ML et alTwelve-month outcome of patients with an established indication for oral anti-coagulation undergoing coronary artery stenting and stratified by the baselinerisk of bleeding insights from the Warfarin and Coronary Stenting (War-Stent)Registry Cardiovasc Revasc Med 201718425ndash30

11 Verlinden NJ Coons JC Iasella CJ Kane-Gill SL Triple antithrombotic therapywith aspirin P2Y12 inhibitor and warfarin after percutaneous coronary inter-vention an evaluation of prasugrel or ticagrelor versus clopidogrel J CardiovascPharmacol Ther 201722546ndash51

12 Faza NN Mentias A Parashar A Chaudhury P Barakat AF Agarwal S et alBleeding complications of triple antithrombotic therapy after percutaneous cor-onary interventions Catheter Cardiovasc Interv 201789E64ndashE74

13 Fauchier L Ruiz-Nodar JM Valdes M Angoulvant D Lip GYH Marın F Is oralanticoagulation needed in patients with atrial fibrillation and stent implantationat low-moderate risk of stroke Eur J Intern Med 201635e9ndashe10

14 Sra S Tan MK Mehta SR Fisher HN Dery J-P Welsh RC et al Ischemic andbleeding events in patients with myocardial infarction undergoing percutaneouscoronary intervention who require oral anticoagulation insights from theCanadian observational AntiPlatelet sTudy Am Heart J 201618082ndash9

15 Bogacki P Kabłak-Ziembicka A Bryniarski K Wrotniak L Ostrowska-Kaim E_Zmudka K et al Triple anticoagulation therapy in patients with atrial fibrillationundergoing percutaneous coronary interventionmdashreal life assessment PostepyKardiol Interwencyjnej 20164303ndash13

16 Fu A Singh K Abunassar J Malhotra N Le May M Labinaz M et al Ticagrelor intriple antithrombotic therapy predictors of ischemic and bleeding complica-tions Clin Cardiol 20163919ndash23

17 Sambola A Mutuberria M Garcia Del Blanco B Alonso A Barrabes JA BuenoH et al Impact of triple therapy in elderly patients with atrial fibrillation under-going percutaneous coronary intervention PLoS One 201611e0147245

18 Lopes RD Rao M Simon DN Thomas L Ansell J Fonarow GC et al Triple vsdual antithrombotic therapy in patients with atrial fibrillation and coronary ar-tery disease Am J Med 2016129592ndash9e1

19 De Vecchis R Cantatrione C Mazzei D Clinical relevance of anticoagulationand dual antiplatelet therapy to the outcomes of patients with atrial fibrillationand recent percutaneous coronary intervention with stent J Clin Med Res 20168153ndash61

20 Koskinas KC Raber L Zanchin T Pilgrim T Stortecky S Hunziker L et alDuration of triple antithrombotic therapy and outcomes among patients under-going percutaneous coronary intervention JACC Cardiovasc Interv 201691473ndash83

21 Secemsky EA Butala NM Kartoun U Mahmood S Wasfy JH Kennedy KF et alUse of chronic oral anticoagulation and associated outcomes among patientsundergoing percutaneous coronary intervention J Am Heart Assoc 20165e004310

22 Sambola A Mutuberria M Garcia Del Blanco B Alonso A Barrabes JA AlfonsoF et al Effects of triple therapy in patients with non-valvular atrial fibrillation un-dergoing percutaneous coronary intervention regarding thromboembolic riskstratification Circ J 201680354ndash62

23 Braun OO Bico B Chaudhry U Wagner H Koul S Tyden P et al Concomitantuse of warfarin and ticagrelor as an alternative to triple antithrombotic therapyafter an acute coronary syndrome Thromb Res 201513526ndash30

24 Hess CN Peterson ED Peng SA de Lemos JA Fosbol EL Thomas L et al Useand outcomes of triple therapy among older patients with acute myocardial in-farction and atrial fibrillation J Am Coll Cardiol 201566616ndash27

25 Mennuni MG Halperin JL Bansilal S Schoos MM Theodoropoulos KN MeeluOA et al Balancing the risk of bleeding and stroke in patients with atrial fibrilla-tion after percutaneous coronary intervention (from the AVIATOR Registry)Am J Cardiol 201511637ndash42

26 Staudacher DL Kaiser M Hehrlein C Bode C Ahrens I Triple antithrombotictherapy after percutaneous coronary intervention (PCI) in patients with indica-tion for oral anticoagulation data from a single center registry PLoS One 201510e0140101

27 Kawai H Watanabe E Yamamoto M Harigaya H Sano K Takatsu H et alMajor bleeding complications related to combined antithrombotic therapy inatrial fibrillation patients 12 months after coronary artery stenting J Cardiol201565197ndash202

28 Jackson LR Ju C Zettler M Messenger JC Cohen DJ Stone GW et alOutcomes of patients with acute myocardial infarction undergoing percutane-ous coronary intervention receiving an oral anticoagulant and dual antiplatelettherapy a comparison of clopidogrel versus prasugrel from the TRANSLATE-ACS study JACC Cardiovasc Interv 201581880ndash9

29 Karrowni W Wang TY Chen AY Thomas L Saucedo JF El Accaoui RNChronic vitamin K antagonist therapy and bleeding risk in ST elevation myocar-dial infarction patients Heart (British Cardiac Society) 2015101264ndash70

30 Enomoto Y Iijima R Tokue M Ito N Nagashima Y Araki T et al Bleeding riskwith triple antithrombotic therapy in patients with atrial fibrillation and drug-eluting stents Cardiovasc Interv Ther 201429193ndash9

31 Rubboli A Schlitt A Kiviniemi T Biancari F Karjalainen PP Valencia J et alOne-year outcome of patients with atrial fibrillation undergoing coronary arterystenting an analysis of the AFCAS registry Clin Cardiol 201437357ndash64

32 Goto K Nakai K Shizuta S Morimoto T Shiomi H Natsuaki M et alAnticoagulant and antiplatelet therapy in patients with atrial fibrillation undergo-ing percutaneous coronary intervention Am J Cardiol 201411470ndash8

33 Alonso A Gore JM Awad HH Quill AL Montalescot G van de Werf F et alManagement and outcomes of patients presenting with STEMI by use of chronicoral anticoagulation results from the GRACE registry Eur Heart J AcuteCardiovasc Care 20132280ndash91

34 Dabrowska M Ochała A Cybulski W Tendera M Balancing between bleedingand thromboembolism after percutaneous coronary intervention in patientswith atrial fibrillation Could triple anticoagulant therapy be a solution PostepyKardiol Interwencyjnej 20133234ndash40

35 Fosbol EL Wang TY Li S Piccini J Lopes RD Mills RM et al Warfarin useamong older atrial fibrillation patients with non-ST-segment elevation myocar-dial infarction managed with coronary stenting and dual antiplatelet therapy AmHeart J 2013166864ndash70

36 Seivani Y Abdel-Wahab M Geist V Richardt G Sulimov DS El-Mawardy Met al Long-term safety and efficacy of dual therapy with oral anticoagulationand clopidogrel in patients with atrial fibrillation treated with drug-elutingstents Clin Res Cardiol 2013102799ndash806

37 Denas G Padayattil Jose S Gresele P Erba N Testa S De Micheli V et alMajor bleeding in patients undergoing PCI and triple or dual antithrombotictherapy a parallel-cohort study J Thromb Thrombolysis 201335178ndash84

38 Chandrasekhar J Mastoris I Baber U Sartori S Schoos M Bansilal S et alAntithrombotic strategy variability in ATrial fibrillation and obstructive coro-nary disease revascularized with PCI-rationale and study design of the prospec-tive observational multicenter AVIATOR 2 registry Am Heart J 20151701234ndash42

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ovember 2018

39 Gibson CM Mehran R Bode C Halperin J Verheugt FW Wildgoose P et alPrevention of bleeding in patients with atrial fibrillation undergoing PCI N Engl JMed 20163752423ndash34

40 Cannon CP Bhatt DL Oldgren J Lip GYH Ellis SG Kimura T et al Dual antith-rombotic therapy with dabigatran after PCI in atrial fibrillation N Engl J Med20173771513ndash24

41 Alexander JH Lopes RD Thomas L Alings M Atar D Aylward P et alApixaban vs warfarin with concomitant aspirin in patients with atrial fibrillationinsights from the ARISTOTLE trial Eur Heart J 201435224ndash32

42 Lopes RD Vora AN Liaw D Granger CB Darius H Goodman SG et al Anopen-Label 2 2 factorial randomized controlled trial to evaluate the safety ofapixaban vs vitamin K antagonist and aspirin vs placebo in patients with atrial fi-brillation and acute coronary syndrome andor percutaneous coronary interven-tion rationale and design of the AUGUSTUS trial Am Heart J 201820017ndash23

43 Vranckx P Lewalter T Valgimigli M Tijssen JG Reimitz PE Eckardt L et alEvaluation of the safety and efficacy of an edoxaban-based antithrombotic regi-men in patients with atrial fibrillation following successful percutaneous coro-nary intervention (PCI) with stent placement rationale and design of theENTRUST-AF PCI trial Am Heart J 2018196105ndash12

44 Golwala HB Cannon CP Steg PG Doros G Qamar A Ellis SG et al Safety andefficacy of dual vs triple antithrombotic therapy in patients with atrial fibrillationfollowing percutaneous coronary intervention a systematic review and meta-analysis of randomized clinical trials Eur Heart J 2018391726ndash35a

45 Dewilde WJM Oirbans T Verheugt FWA Kelder JC De Smet BJGL HerrmanJ-P et al Use of clopidogrel with or without aspirin in patients taking oral anti-coagulant therapy and undergoing percutaneous coronary intervention anopen-label randomised controlled trial Lancet 20133811107ndash15

46 Ohman E Roe M Steg P James S Povsic T White J et al Clinically significantbleeding with low-dose rivaroxaban versus aspirin in addition to P2Y12 inhibi-tion in acute coronary syndromes (GEMINI-ACS-1) a double-blind multi-centre randomised trial Lancet 20173891799ndash808

47 Eikelboom JWCS Bosch J Dagenais GR Hart RG Shestakovska O Diaz Ret al Rivaroxaban with or without aspirin in stable cardiovascular disease NEngl J Med 20173771319ndash30

48 Vranckx P Valgimigli M Windecker S Steg P Hamm C Juni P et al Long-termticagrelor monotherapy versus standard dual antiplatelet therapy followed byaspirin monotherapy in patients undergoing biolimus-eluting stent implantationrationale and design of the GLOBAL LEADERS trial EuroIntervention 2016121239ndash45

49 Baber U Dangas G Cohen DJ Gibson CM Mehta SR Angiolillo DJ et alTicagrelor with aspirin or alone in high-risk patients after coronary interventionrationale and design of the TWILIGHT study Am Heart J 2016182125ndash34

50 Sarafoff N Martischnig A Wealer J Mayer K Mehilli J Sibbing D et al Tripletherapy with aspirin prasugrel and vitamin K antagonists in patients with drug-eluting stent implantation and an indication for oral anticoagulation J Am CollCardiol 2013612060ndash6

51 Wiviott SD Antman EM Gibson CM Montalescot G Riesmeyer JWeerakkody G et al Evaluation of prasugrel compared with clopidogrel inpatients with acute coronary syndromes design and rationale for the TRial toassess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioNwith prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38)Am Heart J 2006152627ndash35

52 Wallentin L Becker RC Budaj A Cannon CP Emanuelsson H Held C et alTicagrelor versus clopidogrel in patients with acute coronary syndromes NEngl J Med 20093611045ndash57

53 Bonaca MP Bhatt DL Braunwald E Cohen M Steg PG Storey RF et al Designand rationale for the prevention of cardiovascular events in patients with priorheart attack using ticagrelor compared to placebo on a background of aspirin-thrombolysis in myocardial infarction 54 (PEGASUS-TIMI 54) trial Am Heart J2014167437ndash44e5

54 Bonaca MP Bhatt DL Cohen M Steg PG Storey RF Jensen EC et al Long-term use of ticagrelor in patients with prior myocardial infarction N Engl J Med20153721791ndash800

55 Storey RF Angiolillo DJ Bonaca MP Thomas MR Judge HM Rollini F et alPlatelet inhibition with ticagrelor 60 mg compared with 90 mg twice-daily inthe PEGASUS-TIMI 54 study J Am Coll Cardiol 2016671145ndash54

56 Sibbing D Aradi D Jacobshagen C Gross L Trenk D Geisler T et al Guidedde-escalation of antiplatelet treatment in patients with acute coronary syn-drome undergoing percutaneous coronary intervention (TROPICAL-ACS) arandomised open-label multicentre trial Lancet 20173901747ndash57

57 Cuisset T Deharo P Quilici J Johnson TW Deffarges S Bassez C et al Benefitof switching dual antiplatelet therapy after acute coronary syndrome theTOPIC (timing of platelet inhibition after acute coronary syndrome) random-ized study Eur Heart J 2017383070ndash8

58 Kowalewski M Suwalski P Raffa GM Słomka A Kowalkowska ME Szwed KA et alMeta-analysis of uninterrupted as compared to interrupted oral anticoagulation

with or without bridging in patients undergoing coronary angiography with or with-out percutaneous coronary intervention Int J Cardiol 2016223186ndash94

59 Kolh P Windecker S Alfonso F Collet J-P Cremer J Falk V et al ESCEACTSmyocardial revascularization guidelines 2014 Eur Heart J 201446 517ndash6

60 Valgimigli M Patialiakas A Thury A McFadden E Colangelo S Campo G et alZotarolimus-eluting versus bare-metal stents in uncertain drug-eluting stentcandidates J Am Coll Cardiol 201565805ndash15

61 Urban P Meredith IT Abizaid A Pocock SJ Carrie D Naber C et al Polymer-free drug-coated coronary stents in patients at high bleeding risk N Engl J Med20153732038ndash47

62 Naber CK Urban P Ong PJ Valdes-Chavarri M Abizaid AA Pocock SJ et alBiolimus-A9 polymer-free coated stent in high bleeding risk patients withacute coronary syndrome a Leaders Free ACS sub-study Eur Heart J 201738961ndash9

63 Garot P Morice MC Tresukosol D Pocock SJ Meredith IT Abizaid A et al 2-Year outcomes of high bleeding risk patients after polymer-free drug-coatedstents J Am Coll Cardiol 201769162ndash71

64 Carrie D Menown I Oldroyd K Copt S Talwar S Maillard L et al Safety andefficacy of polymer-free biolimus A9-coated versus bare-metal stents in orallyanticoagulated patients 2-year results of the LEADERS FREE oral anticoagula-tion substudy JACC Cardiovasc Interv 2017101633ndash42

65 Varenne O Cook S Sideris G Kedev S Cuisset T Carrie D et al Drug-elutingstents in elderly patients with coronary artery disease (SENIOR) a randomisedsingle-blind trial Lancet 201839141ndash50

66 Byrne RA Serruys PW Baumbach A Escaned J Fajadet J James S et al Reportof a European Society of Cardiology-European Association of PercutaneousCardiovascular Interventions task force on the evaluation of coronary stents inEurope executive summary Eur Heart J 2015362608ndash20

67 Byrne RA Stefanini GG Capodanno D Onuma Y Baumbach A Escaned J et alReport of an ESC-EAPCI Task Force on the evaluation and use of bioresorb-able scaffolds for percutaneous coronary intervention executive summaryEuroIntervention 2018131574ndash86

68 Cassese S Byrne RA Juni P Wykrzykowska JJ Puricel S Ndrepepa G et alMidterm clinical outcomes with everolimus-eluting bioresorbable scaffoldsversus everolimus-eluting metallic stents for percutaneous coronary inter-ventions a meta-analysis of randomised trials EuroIntervention 2018131565ndash73

69 Rodes-Cabau J Dauerman HL Cohen MG Mehran R Small EM Smyth SS et alAntithrombotic treatment in transcatheter aortic valve implantation insights forcerebrovascular and bleeding events J Am Coll Cardiol 2013622349ndash59

70 Leon MB Smith CR Mack M Miller DC Moses JW Svensson LG et alTranscatheter aortic-valve implantation for aortic stenosis in patients who can-not undergo surgery N Engl J Med 20103631597ndash607

71 Smith CR Leon MB Mack MJ Miller DC Moses JW Svensson LG et alTranscatheter versus surgical aortic-valve replacement in high-risk patients NEngl J Med 20113642187ndash98

72 Adams DH Popma JJ Reardon MJ Yakubov SJ Coselli JS Deeb GM et alTranscatheter aortic-valve replacement with a self-expanding prosthesis N EnglJ Med 20143701790ndash8

73 Hamm CW Mollmann H Holzhey D Beckmann A Veit C Figulla HR et alThe German Aortic Valve Registry (GARY) in-hospital outcome Eur Heart J2014351588ndash98

74 Gargiulo G Sannino A Capodanno D Barbanti M Buccheri S Perrino Cet al Transcatheter aortic valve implantation versus surgical aortic valve re-placement a systematic review and meta-analysis Ann Intern Med 2016165334ndash44

75 Siontis GC Praz F Pilgrim T Mavridis D Verma S Salanti G et alTranscatheter aortic valve implantation vs surgical aortic valve replacement fortreatment of severe aortic stenosis a meta-analysis of randomized trials EurHeart J 2016373503ndash12

76 Ussia GP Scarabelli M Mule M Barbanti M Sarkar K Cammalleri V et al Dualantiplatelet therapy versus aspirin alone in patients undergoing transcatheteraortic valve implantation Am J Cardiol 20111081772ndash6

77 Stabile E Pucciarelli A Cota L Sorropago G Tesorio T Salemme L et al SAT-TAVI (single antiplatelet therapy for TAVI) study a pilot randomized studycomparing double to single antiplatelet therapy for transcatheter aortic valveimplantation Int J Cardiol 2014174624ndash7

78 Holmes DR Jr Mack MJ Kaul S Agnihotri A Alexander KP Bailey SR et al2012 ACCFAATSSCAISTS expert consensus document on transcatheteraortic valve replacement J Am Coll Cardiol 2012591200ndash54

79 Vahanian A Alfieri O Andreotti F Antunes MJ Baron-Esquivias GBaumgartner H et al Guidelines on the management of valvular heart disease(version 2012) Eur Heart J 2012332451ndash96

80 Webb J Rodes-Cabau J Fremes S Pibarot P Ruel M Ibrahim R et alTranscatheter aortic valve implantation a Canadian Cardiovascular Society po-sition statement Can J Cardiol 201228520ndash8

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ovember 2018

81 Whitlock RP Sun JC Fremes SE Rubens FD Teoh KH Antithrombotic andthrombolytic therapy for valvular disease antithrombotic Therapy andPrevention of Thrombosis 9th ed american College of Chest PhysiciansEvidence-Based Clinical Practice Guidelines Chest 2012141e576Sndash600S

82 Gargiulo G Collet JP Valgimigli M Antithrombotic therapy in TAVI patientschanging concepts EuroIntervention 201511(Suppl W)W92ndash5

83 Dangas GD Lefevre T Kupatt C Tchetche D Schafer U Dumonteil N et alBivalirudin versus heparin anticoagulation in transcatheter aortic valve replace-ment the randomized BRAVO-3 trial J Am Coll Cardiol 2015662860ndash8

84 Nijenhuis VJ Bennaghmouch N van Kuijk JP Capodanno D ten Berg JMAntithrombotic treatment in patients undergoing transcatheter aortic valve im-plantation (TAVI) Thromb Haemost 2015113674ndash85

85 Di Mario C Eltchaninoff H Moat N Goicolea J Ussia GP Kala P et al The2011-12 pilot European Sentinel Registry of Transcatheter Aortic ValveImplantation in-hospital results in 4 571 patients EuroIntervention 201381362ndash71

86 Gilard M Eltchaninoff H Iung B Donzeau-Gouge P Chevreul K Fajadet J et alRegistry of transcatheter aortic-valve implantation in high-risk patients N Engl JMed 20123661705ndash15

87 Sannino A Gargiulo G Schiattarella GG Perrino C Stabile E Losi MA et al Ameta-analysis of the impact of pre-existing and new-onset atrial fibrillation onclinical outcomes in patients undergoing transcatheter aortic valve implantationEuroIntervention 201612e1047ndashe56

88 Rodes-Cabau J Masson JB Welsh RC Garcia Del Blanco B Pelletier M WebbJG et al Aspirin versus aspirin plus clopidogrel as antithrombotic treatment fol-lowing transcatheter aortic valve replacement with a balloon-expandable valvethe ARTE (Aspirin Versus Aspirin thorn Clopidogrel Following TranscatheterAortic Valve Implantation) randomized clinical trial JACC Cardiovasc Interv 2017101357ndash65

89 Capodanno D Angiolillo DJ Antithrombotic therapy for prevention of cerebralthromboembolic events after transcatheter aortic valve replacement evolvingparadigms and ongoing directions JACC Cardiovasc Interv 2017101366ndash9

90 Windecker S Tijssen J Giustino G Guimaraes AH Mehran R Valgimigli Met al Trial design rivaroxaban for the prevention of major cardiovascular eventsafter transcatheter aortic valve replacement rationale and design of theGALILEO study Am Heart J 201718481ndash7

91 Nijenhuis VJ Bennaghmouch N Hassell M Baan J Jr van Kuijk JP Agostoni Pet al Rationale and design of POPular-TAVI antiPlatelet therapy fOr Patientsundergoing Transcatheter Aortic Valve Implantation Am Heart J 201617377ndash85

92 Feldman T Kar S Elmariah S Smart SC Trento A Siegel RJ et al Randomizedcomparison of percutaneous repair and surgery for mitral regurgitation 5-yearresults of EVEREST II J Am Coll Cardiol 2015662844ndash54

93 Whitlow PL Feldman T Pedersen WR Lim DS Kipperman R Smalling R et alAcute and 12-month results with catheter-based mitral valve leaflet repair theEVEREST II (Endovascular Valve Edge-to-Edge Repair) High Risk Study J AmColl Cardiol 201259130ndash9

94 Yoon SH Whisenant BK Bleiziffer S Delgado V Schofer N Eschenbach L et alTranscatheter mitral valve replacement for degenerated bioprosthetic valvesand failed annuloplasty rings J Am Coll Cardiol 2017701121ndash31

95 Blackshear JL Odell JA Appendage obliteration to reduce stroke in cardiac sur-gical patients with atrial fibrillation Ann Thorac Surg 199661755ndash9

96 Peritz DC Chung EH Left atrial appendage closure an emerging option in atrialfibrillation when oral anticoagulants are not tolerated Cleve Clin J Med 201582167ndash76

97 Holmes DR Reddy VY Turi ZG Doshi SK Sievert H Buchbinder M et alPercutaneous closure of the left atrial appendage versus warfarin therapy forprevention of stroke in patients with atrial fibrillation a randomised non-inferiority trial Lancet 2009374534ndash42

98 Holmes DR Jr Kar S Price MJ Whisenant B Sievert H Doshi SK et alProspective randomized evaluation of the Watchman Left Atrial AppendageClosure device in patients with atrial fibrillation versus long-term warfarin ther-apy the PREVAIL trial J Am Coll Cardiol 2014641ndash12

99 Mandrola J Foy A Naccarelli G Percutaneous left atrial appendage closure isnot ready for routine clinical use Heart Rhythm 201815298ndash301

100 Fauchier L Cinaud A Brigadeau F Lepillier A Pierre B Abbey S et al Device-related thrombosis after percutaneous left atrial appendage occlusion for atrialfibrillation J Am Coll Cardiol 2018711528ndash36

101 Landmesser U Schmidt B Nielsen-Kudsk JE Lam SCC Park JW Tarantini Get al Left atrial appendage occlusion with the AMPLATZER Amulet deviceperiprocedural and early clinicalechocardiographic data from a global prospec-tive observational study EuroIntervention 201713867ndash76

102 Tzikas A Shakir S Gafoor S Omran H Berti S Santoro G et al Leftatrial appendage occlusion for stroke prevention in atrial fibrillation multicentreexperience with the AMPLATZER Cardiac Plug EuroIntervention 2016111170ndash9

103 Urena M Rodes-Cabau J Freixa X Saw J Webb JG Freeman M et alPercutaneous left atrial appendage closure with the AMPLATZER cardiac plugdevice in patients with nonvalvular atrial fibrillation and contraindications toanticoagulation therapy J Am Coll Cardiol 20136296ndash102

104 Lakkireddy D Afzal MR Lee RJ Nagaraj H Tschopp D Gidney B et al Shortand long-term outcomes of percutaneous left atrial appendage suture ligationresults from a US multicenter evaluation Heart Rhythm 2016131030ndash6

105 Lip GYH Freedman B De Caterina R Potpara TS Stroke prevention in atrial fi-brillation past present and future Comparing the guidelines and practical deci-sion-making Thromb Haemost 20171171230ndash9

106 Fauchier L Lecoq C Ancedy Y Stamboul K Saint Etienne C Ivanes F et alEvaluation of 5 prognostic scores for prediction of stroke thromboembolic andcoronary events all-cause mortality and major adverse cardiac events inpatients with atrial fibrillation and coronary stenting Am J Cardiol 2016118700ndash7

107 Capodanno D Rossini R Musumeci G Lettieri C Senni M Valsecchi O et alPredictive accuracy of CHA2DS2-VASc and HAS-BLED scores in patients with-out atrial fibrillation undergoing percutaneous coronary intervention and dis-charged on dual antiplatelet therapy Int J Cardiol 2015199319ndash25

108 Singer DE Chang Y Borowsky LH Fang MC Pomernacki NK Udaltsova Net al A new risk scheme to predict ischemic stroke and other thromboembo-lism in atrial fibrillation the ATRIA study stroke risk score J Am Heart Assoc20132e000250

109 Hippisley-Cox J Coupland C Brindle P Derivation and validation of QStrokescore for predicting risk of ischaemic stroke in primary care and comparisonwith other risk scores a prospective open cohort study BMJ 2013346f2573

110 Hijazi Z Lindback J Alexander JH Hanna M Held C Hylek EM et al The ABC(age biomarkers clinical history) stroke risk score a biomarker-based riskscore for predicting stroke in atrial fibrillation Eur Heart J 2016371582ndash90

111 Rivera-Caravaca JM Roldan V Esteve-Pastor MA Valdes M Vicente V LipGYH et al Long-term stroke risk prediction in patients with atrial fibrillationcomparison of the ABC-stroke and CHA2DS2-VASc scores J Am Heart Assoc20176e006490

112 Roldan V Rivera-Caravaca JM Shantsila A Garcia-Fernandez A Esteve-PastorMA Vilchez JA et al Enhancing the 0real world0 prediction of cardiovascularevents and major bleeding with the CHA2DS2-VASc and HAS-BLED scores us-ing multiple biomarkers Ann Med 20185026ndash34

113 Chao TF Lip GYH Liu CJ Lin YJ Chang SL Lo LW et al Relationship of agingand incident comorbidities to stroke risk in patients with atrial fibrillation J AmColl Cardiol 201871122ndash32

114 Yoon M Yang PS Jang E Yu HT Kim TH Uhm JS et al Dynamic changes ofCHA2DS2-VASc score and the risk of ischaemic stroke in asian patients withatrial fibrillation a Nationwide Cohort Study Thromb Haemost 20181181296ndash1304

115 Pisters R Lane DA Nieuwlaat R de Vos CB Crijns HJGM Lip GYH A noveluser-friendly score (HAS-BLED) to assess 1-year risk of major bleeding inpatients with atrial fibrillation the Euro Heart Survey Chest 20101381093ndash100

116 Fang MC Go AS Chang Y Borowsky LH Pomernacki NK Udaltsova N et al Anew risk scheme to predict warfarin-associated hemorrhage the ATRIA(Anticoagulation and Risk Factors in Atrial Fibrillation) Study J Am Coll Cardiol201158395ndash401

117 OrsquoBrien EC Simon DN Thomas LE Hylek EM Gersh BJ Ansell JE et al TheORBIT bleeding score a simple bedside score to assess bleeding risk in atrial fi-brillation Eur Heart J 2015363258ndash64

118 Hijazi Z Oldgren J Lindback J Alexander JH Connolly SJ Eikelboom JW et alThe novel biomarker-based ABC (age biomarkers clinical history)-bleeding riskscore for patients with atrial fibrillation a derivation and validation study Lancet20163872302ndash11

119 Roldan V Marin F Manzano-Fernandez S Gallego P Vilchez JA Valdes M et alThe HAS-BLED score has better prediction accuracy for major bleeding thanCHADS2 or CHA2DS2-VASc scores in anticoagulated patients with atrial fibril-lation J Am Coll Cardiol 2013622199ndash204

120 Apostolakis S Lane DA Buller H Lip GY Comparison of the CHADS2CHA2DS2-VASc and HAS-BLED scores for the prediction of clinically relevantbleeding in anticoagulated patients with atrial fibrillation the AMADEUS trialThromb Haemost 20131101074ndash9

121 Guo YT Zhang Y Shi XM Shan ZL Wang CJ Wang YT et al Assessing bleed-ing risk in 4824 Asian patients with atrial fibrillation the Beijing PLA HospitalAtrial Fibrillation Project Sci Rep 2016631755

122 Guo Y Zhu H Chen Y Lip GYH Comparing bleeding risk assessment focusedon modifiable risk factors only versus validated bleeding risk scores in atrial fi-brillation Am J Med 2018131185ndash92

123 Wang C Yu Y Zhu W Yu J Lip GYH Hong K Comparing the ORBIT andHAS-BLED bleeding risk scores in anticoagulated atrial fibrillation patients asystematic review and meta-analysis Oncotarget 20178109703ndash11

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ovember 2018

124 Rivera-Caravaca JM Roldan V Esteve-Pastor MA Valdes M Vicente V LipGYH et al Importance of time in therapeutic range on bleeding risk predictionusing clinical risk scores in patients with atrial fibrillation Sci Rep 2017712066

125 Proietti M Senoo K Lane DA Lip GY Major bleeding in patients with non-valvular atrial fibrillation impact of time in therapeutic range on contemporarybleeding risk scores Sci Rep 2016624376

126 Proietti M Hijazi Z Andersson U Connolly SJ Eikelboom JW Ezekowitz MDet al Comparison of bleeding risk scores in patients with atrial fibrillationinsights from the RE-LY trial J Intern Med 2018283282ndash92

127 Esteve-Pastor MA Rivera-Caravaca JM Roldan V Vicente V Valdes M Marin Fet al Long-term bleeding risk prediction in 0real world0 patients with atrial fibril-lation comparison of the HAS-BLED and ABC-Bleeding risk scores The MurciaAtrial Fibrillation Project Thromb Haemost 20171171848ndash58

128 Costa F van Klaveren D James S Heg D Raber L Feres F et al Derivation andvalidation of the predicting bleeding complications in patients undergoing stentimplantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) scorea pooled analysis of individual-patient datasets from clinical trials Lancet 20173891025ndash34

129 Lip GYH Skjoth F Nielsen PB Kjaeldgaard JN Larsen TB The HAS-BLEDATRIA and ORBIT bleeding scores in atrial fibrillation patients using non-vitamin K antagonist oral anticoagulants Am J Med 2017131574e13ndash27

130 Ruiz-Nodar JM Marın F Roldan V Valencia J Manzano-Fernandez S CaballeroL et al Should we recommend oral anticoagulation therapy in patients withatrial fibrillation undergoing coronary artery stenting with a high HAS-BLEDbleeding risk score Circ Cardiovasc Interv 20125459ndash66

131 Smith JG Wieloch M Koul S Braun OO Lumsden J Rydell E et al Tripleantithrombotic therapy following an acute coronary syndrome prevalence out-comes and prognostic utility of the HAS-BLED score EuroIntervention 20128672ndash8

132 Chao TF Lip GYH Lin YJ Chang SL Lo LW Hu YF et al Incident risk factorsand major bleeding in patients with atrial fibrillation treated with oral anticoagu-lants a comparison of baseline follow-up and delta HAS-BLED scores with anapproach focused on modifiable bleeding risk factors Thromb Haemost 2018118768ndash77

133 Wilson PWF DrsquoAgostino R Bhatt DL Eagle K Pencina MJ Smith SC et al Aninternational model to predict recurrent cardiovascular disease Am J Med 2012125695ndash703e1

134 Girasis C Garg S Raber L Sarno G Morel M-A Garcia-Garcia HM et alSYNTAX score and Clinical SYNTAX score as predictors of very long-termclinical outcomes in patients undergoing percutaneous coronary interventionsa substudy of SIRolimus-eluting stent compared with pacliTAXel-eluting stentfor coronary revascularization (SIRTAX) trial Eur Heart J 2011323115ndash27

135 Fox KAA Dabbous OH Goldberg RJ Pieper KS Eagle KA Van de Werf F et alPrediction of risk of death and myocardial infarction in the six months after pre-sentation with acute coronary syndrome prospective multinational observa-tional study (GRACE) BMJ 20063331091

136 Chao TF Lip GYH Lin YJ Chang SL Lo LW Hu YF et al Major bleeding andintracranial hemorrhage risk prediction in patients with atrial fibrillation atten-tion to modifiable bleeding risk factors or use of a bleeding risk stratificationscore A nationwide cohort study Int J Cardiol 2018254157ndash61

137 Esteve-Pastor M Rivera-Caravaca J Shantsila A Roldan V Lip G Marın FAssessing bleeding risk in atrial fibrillation patients comparing a bleeding riskscore based only on modifiable bleeding risk factors against the HAS-BLEDscore The AMADEUS trial Thromb Haemost 20171172261ndash6

138 Connolly S Pogue J Hart R Pfeffer M Hohnloser S Chrolavicius S et alClopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in theAtrial fibrillation Clopidogrel Trial with Irbesartan for prevention of VascularEvents (ACTIVE W) a randomised controlled trial Lancet 20063671903ndash12

139 Fanola CL Giugliano RP Ruff CT Trevisan M Nordio F Mercuri MF et al Anovel risk prediction score in atrial fibrillation for a net clinical outcome fromthe ENGAGE AF-TIMI 48 randomized clinical trial Eur Heart J 201738888ndash96

140 Rivera-Caravaca JM Roldan V Esteve-Pastor MA Valdes M Vicente V Marin Fet al Prediction of long-term net clinical outcomes using the TIMI-AF scorecomparison with CHA2DS2-VASc and HAS-BLED Am Heart J 201819727ndash34

141 Rivera-Caravaca JM Marın F Esteve-Pastor MA Ra~na-Mıguez P Anguita MMu~niz J et al Usefulness of the 2MACE score to predicts adverse cardiovascularevents in patients with atrial fibrillation Am J Cardiol 20171202176ndash81

142 Pastori D Rivera-Caravaca JM Esteve-Pastor MA Roldan V Marin F PignatelliP et al Comparison of the 2MACE and TIMI-AF scores for composite clinicaloutcomes in anticoagulated atrial fibrillation patients Circ J 2018821286ndash92

143 Windecker S Kolh P Alfonso F Collet JP Cremer J et al 2014 ESCEACTSGuidelines on myocardial revascularization the Task Force on MyocardialRevascularization of the European Society of Cardiology (ESC) and theEuropean Association for Cardio-Thoracic Surgery (EACTS)Developed with

the special contribution of the European Association of PercutaneousCardiovascular Interventions (EAPCI) Eur Heart J 2014352541ndash619

144 Levine GN Bates ER Bittl JA Brindis RG Fihn SD Fleisher LA et al 2016ACCAHA Guideline focused update on duration of dual antiplatelet therapy inpatients with coronary artery disease a report of the American College ofCardiologyAmerican Heart Association Task Force on Clinical PracticeGuidelines an Update of the 2011 ACCFAHASCAI Guideline forPercutaneous Coronary Intervention 2011 ACCFAHA Guideline forCoronary Artery Bypass Graft Surgery 2012 ACCAHAACPAATSPCNASCAISTS Guideline for the Diagnosis and Management of Patients With StableIschemic Heart Disease 2013 ACCFAHA Guideline for the Management ofST-Elevation Myocardial Infarction 2014 AHAACC Guideline for theManagement of Patients With Non-ST-Elevation Acute Coronary Syndromesand 2014 ACCAHA Guideline on Perioperative Cardiovascular Evaluation andManagement of Patients Undergoing Noncardiac Surgery Circulation 2016134e192ndash55

145 Mazurek M Huisman MV Rothman KJ Paquette M Teutsch C Diener HC et alRegional differences in antithrombotic treatment for atrial fibrillation insights fromthe GLORIA-AF Phase II Registry Thromb Haemost 20171172376ndash88

146 Alsolamy S Al-Sabhan A Alassim N Sadat M Qasim EA Tamim H et alManagement and outcomes of patients presenting with sepsis and septic shockto the emergency department during nursing handover a retrospective cohortstudy BMC Emerg Med 2018183

147 Fiedler KA Maeng M Mehilli J Schulz-Schupke S Byrne RA Sibbing D et alDuration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent implantation the ISAR-TRIPLE trial J Am Coll Cardiol 2015651619ndash29

148 Dewilde WJ Oirbans T Verheugt FW Kelder JC De Smet BJ Herrman JPet al Use of clopidogrel with or without aspirin in patients taking oral anticoag-ulant therapy and undergoing percutaneous coronary intervention an open-label randomised controlled trial Lancet 20133811107ndash15

149 Kiviniemi T Airaksinen KE Rubboli A Biancari F Valencia J Lip GY et alBridging therapy with low molecular weight heparin in patients with atrial fibril-lation undergoing percutaneous coronary intervention with stent implantationthe AFCAS study Int J Cardiol 2015183105ndash10

150 Baker NC OrsquoConnell EW Htun WW Sun H Green SM Skelding KA et alSafety of coronary angiography and percutaneous coronary intervention via theradial versus femoral route in patients on uninterrupted oral anticoagulationwith warfarin Am Heart J 2014168537ndash44

151 Vranckx P Verheugt FW de Maat MP Ulmans VA Regar E Smits P et al Arandomised study of dabigatran in elective percutaneous coronary interventionin stable coronary artery disease patients EuroIntervention 201381052ndash60

152 Vranckx P Leebeek FW Tijssen JG Koolen J Stammen F Herman JP et al Peri-procedural use of rivaroxaban in elective percutaneous coronary interventionto treat stable coronary artery disease The X-PLORER trial Thromb Haemost2015114258ndash67

153 Lahtela H Karjalainen PP Niemela M Vikman S Kervinen K Ylitalo A et al Areglycoprotein inhibitors safe during percutaneous coronary intervention inpatients on chronic warfarin treatment Thromb Haemost 20091021227ndash33

154 Pancholy SB Ahmed I Bertrand OF Patel T Frequency of radial artery occlu-sion after transradial access in patients receiving warfarin therapy and undergo-ing coronary angiography Am J Cardiol 2014113211ndash4

155 Niccoli G Banning AP Heparin dose during percutaneous coronary interven-tion how low dare we go Heart 200288331ndash4

156 Chang RJ Doherty TM Goldberg SL How does warfarin affect the activatedcoagulation time Am Heart J 1998136477ndash9

157 Lincoff AM Bittl JA Harrington RA Feit F Kleiman NS Jackman JD et alBivalirudin and provisional glycoprotein IIbIIIa blockade compared with heparinand planned glycoprotein IIbIIIa blockade during percutaneous coronary inter-vention REPLACE-2 randomized trial JAMA 2003289853ndash63

158 Kiviniemi T Karjalainen P Niemela M Rubboli A Lip GY Schlitt A et alBivalirudin use during percutaneous coronary intervention in patients onchronic warfarin therapy Thromb Res 2014133695ndash6

159 Di Sciascio G Patti G Pasceri V Gatto L Colonna G Montinaro AEffectiveness of in-laboratory high-dose clopidogrel loading versus routine pre-load in patients undergoing percutaneous coronary intervention results of theARMYDA-5 PRELOAD (Antiplatelet therapy for Reduction of MYocardialDamage during Angioplasty) randomized trial J Am Coll Cardiol 201056550ndash7

160 Hochholzer W Trenk D Frundi D Blanke P Fischer B Andris K et al Time de-pendence of platelet inhibition after a 600-mg loading dose of clopidogrel in alarge unselected cohort of candidates for percutaneous coronary interventionCirculation 20051112560ndash4

161 Awtry EH Loscalzo J Aspirin Circulation 20001011206ndash18162 Payne CD Li YG Small DS Ernest CS Farid NA Jakubowski JA et al Increased

active metabolite formation explains the greater platelet inhibition with prasu-grel compared to high-dose clopidogrel J Cardiovasc Pharmacol 200750555ndash62

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163 Dominguez-Rodriguez A Abreu-Gonzalez P Avanzas P Bosa-Ojeda F Samimi-Fard S Marrero-Rodriguez F et al Intracoronary versus intravenous abciximabadministration in patients with ST-elevation myocardial infarction undergoingthrombus aspiration during primary percutaneous coronary interventionmdasheffects on soluble CD40 ligand concentrations Atherosclerosis 2009206523ndash7

164 Ibanez B James S Agewall S Antunes MJ Bucciarelli-Ducci C Bueno H et alESC Scientific Document Group 2017 ESC Guidelines for the management ofacute myocardial infarction in patients presenting with ST-segment elevationThe Task Force for the management of acute myocardial infarction in patientspresenting with ST-segment elevation of the European Society of Cardiology(ESC) Eur Heart J 201839119ndash77

165 Roffi M Patrono C Collet JP Mueller C Valgimigli M Andreotti F et al 2015ESC Guidelines for the management of acute coronary syndromes in patientspresenting without persistent ST-segment elevation task Force for theManagement of Acute Coronary Syndromes in Patients Presenting withoutPersistent ST-Segment Elevation of the European Society of Cardiology (ESC)Eur Heart J 201637267ndash315

166 Valgimigli M Gagnor A Calabro P Frigoli E Leonardi S Zaro T et al Radial ver-sus femoral access in patients with acute coronary syndromes undergoing inva-sive management a randomised multicentre trial Lancet 20153852465ndash76

168 Dewilde WJ Janssen PW Kelder JC Verheugt FW De Smet BJ Adriaenssens Tet al Uninterrupted oral anticoagulation versus bridging in patients with long-term oral anticoagulation during percutaneous coronary intervention subgroupanalysis from the WOEST trial EuroIntervention 201511381ndash90

169 Kang SH Chae IH Park JJ Lee HS Kang DY Hwang SS et al Stent thrombosiswith drug-eluting stents and bioresorbable scaffolds evidence from a networkmeta-analysis of 147 trials JACC Cardiovasc Interv 201691203ndash12

170 Granger CB Alexander JH McMurray JJ Lopes RD Hylek EM Hanna M et alApixaban versus warfarin in patients with atrial fibrillation N Engl J Med 2011365981ndash92

171 Giugliano RP Ruff CT Braunwald E Murphy SA Wiviott SD Halperin JL et alEdoxaban versus warfarin in patients with atrial fibrillation N Engl J Med 20133692093ndash104

172 Gorenek B Blomstrom Lundqvist C Brugada Terradellas J Camm AJ Hindricks GHuber K et al Cardiac arrhythmias in acute coronary syndromes position paperfrom the joint EHRA ACCA and EAPCI task force Europace 2014161655ndash73

173 Zeymer U Annemans L Danchin N Pocock S Newsome S Van de Werf Fet al Impact of known or new-onset atrial fibrillation on 2-year cardiovascularevent rate in patients with acute coronary syndromes results from the pro-spective EPICOR Registry Eur Heart J Acute Cardiovasc Care 2018 doi1011772048872618769057

174 Rivera-Caravaca JM Roldan V Esteve-Pastor MA Valdes M Vicente V LipGYH et al Cessation of oral anticoagulation is an important risk factor forstroke and mortality in atrial fibrillation patients Thromb Haemost 20171171448ndash54

175 Rubboli A Agewall S Huber K Lip GYH New-onset atrial fibrillation after per-cutaneous coronary intervention with stent updated proposal of an algorithmfor the choice of oral anticoagulant and its dose Eur J Intern Med 201740e11ndash12

176 Hurlen M Abdelnoor M Smith P Erikssen J Arnesen H Warfarin aspirin orboth after myocardial infarction N Engl J Med 2002347969ndash74

177 Hamon M Lemesle G Tricot O Meurice T Deneve M Dujardin X et alIncidence source determinants and prognostic impact of major bleeding inoutpatients with stable coronary artery disease J Am Coll Cardiol 2014641430ndash6

178 Proietti M Lip GYH Impact of quality of anticoagulation control on outcomesin patients with atrial fibrillation taking aspirin an analysis from the SPORTIF tri-als Int J Cardiol 201825296ndash100

179 Gibson CM Mehran R Bode C Halperin J Verheugt F Wildgoose P et al Anopen-label randomized controlled multicenter study exploring two treatmentstrategies of rivaroxaban and a dose-adjusted oral vitamin K antagonist treat-ment strategy in subjects with atrial fibrillation who undergo percutaneous cor-onary intervention (PIONEER AF-PCI) Am Heart J 2015169472ndash8

180 Gibson CM Kirtane AJ Murphy SA Rohrbeck S Menon V Lins J et alTIMI Study Group Early initiation of eptifibatide in the emergency depart-ment before primary percutaneous coronary intervention for ST-segmentelevation myocardial infarction results of the Time to Integrilin Therapy inAcute Myocardial Infarction (TITAN)-TIMI 34 trial Am Heart J 2006152668ndash75

181 Bomicke T Valina CM Stratz C Amann M Neumann FJ Hochholzer W On-clopidogrel platelet reactivity as predictor for long-term clinical outcome inpatients after planned discontinuation of clopidogrel Thromb Haemost 20171171644ndash50

182 Reny JL Fontana P Hochholzer W Neumann FJ Ten Berg J Janssen PW et alVascular risk levels affect the predictive value of platelet reactivity for the oc-currence of MACE in patients on clopidogrel Systematic review and meta-analysis of individual patient data Thromb Haemost 2016115844ndash55

183 Podda GM Cattaneo M High on treatment platelet reactivity as a risk factorfor adverse left ventricular remodelling after STEMI Thromb Haemost 2017117829

184 Jamasbi J Ayabe K Goto S Nieswandt B Peter K Siess W Platelet receptorsas therapeutic targets past present and future Thromb Haemost 20171171249ndash57

185 Weitz JI Harenberg J New developments in anticoagulants past present andfuture Thromb Haemost 20171171283ndash8

186 Dimitropoulos G Rahim SMZ Moss AS Lip GYH New anticoagulants for ve-nous thromboembolism and atrial fibrillation what the future holds Expert OpinInvestig Drugs 20182771ndash86

187 Weitz JI Fredenburgh JC 2017 Scientific Sessions Sol sherry distinguished lec-ture in thrombosis factor XI as a target for new anticoagulants ArteriosclerThromb Vasc Biol 201838304ndash10

188 Buller HR Bethune C Bhanot S Gailani D Monia BP Raskob GE et al FactorXI antisense oligonucleotide for prevention of venous thrombosis N Engl J Med2015372232ndash40

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ESC Scientific Document Group Tatjana Potpara (Review Coordinator)20

Carina Blomstrom Lundqvist21 Harry Crijns22 Jan Steffel23 Hein Heidbuchel24

Goran Stankovic25 Juhani Airaksinen26 Jurrien M Ten Berg27 Davide Capodanno28

Stefan James29 Hector Bueno3031 Joao Morais32 Dirk Sibbing33 Bianca Rocca34

Ming-Hsiung Hsieh35 Nazem Akoum36 Deborah J Lockwood37

Jorge Rafael Gomez Flores38 Ronald Jardine39

1Institute of Cardiovascular Sciences University of Birmingham UK 2Liverpool Centre for Cardiovascular Science University of Liverpool and Liverpool Heart amp Chest HospitalLiverpool UK 3Department of Clinical Medicine Aalborg Thrombosis Research Unit Aalborg University Aalborg Denmark 4Sorbonne Universite Paris 6 ACTION StudyGroup (wwwaction-coeurorg) Institut de Cardiologie Hopital Pitie-Salpetriere (APHP) INSERM UMRS Paris France 5Stadtische Kliniken Neuss Lukaskrankenhaus GmbhKardiologie Nephrologie Pneumologie Neuss Germany 6Deutsches Herzzentrum Muenchen Munich Germany 7DZHK (German Centre for Cardiovascular Research)partner site Munich Heart Alliance Munich Germany 8University of North Carolina at Chapel Hill Medicine Cardiology Electrophysiology Chapel Hill NC USA 9CentreHospitalier Universitaire Trousseau et Faculte de MedecinemdashUniversite Francois Rabelais Tours France 10Department of Cardiology Oslo University Hospital Ulleval andInstitute of Clinical Medicine University of Oslo Oslo Norway 11Centre for Heart Rhythm Disorders South Australian Health and Medical Research Institute University ofAdelaide and Royal Adelaide Hospital Adelaide Australia 12Clinica Adventista Belgrano Instituto Del Corazon Buenos Aires Argentina 13Cardiology Department HumanitasResearch Hospital Rozzano MI Italy 14Department of Cardiology Hospital Universitario Virgen de la Arrixaca Murcia Spain 15Milpark Hospital Cardiology Unit JohannesburgSouth Africa 16Division of Cardiology Laboratory of Interventional Cardiology Ospedale Maggiore Bologna Italy 17Department of Infection Immunity and Cardiovascular DiseaseUniversity of Sheffield Sheffield UK 18Inselspital Cardiology Bern Switzerland 193rd Department of Medicine Cardiology and Intensive Care Medicine Wilhelminenhospital ViennaVienna Austria 20School of Medicine Belgrade University Cardiology Clinic Clinical Centre of Serbia Belgrade Serbia 21Department of Medical Science and Cardiology UppsalaUniversity Uppsala Sweden 22Cardiology Department Maastricht UMCthorn Maastricht Netherlands 23University Heart Center Zurich Zurich Switzerland 24Antwerp Universityand University Hospital Antwerp Belgium 25Department of Cardiology Clinical Center of Serbia Belgrade Serbia 26Turku University Hospital Cardiology Department of InternalMedicine Turku Finland 27St Antonius Hospital Cardiology Department Nieuwegein Netherlands 28Ferrarotto Hospital Azienda Ospedaliero-Univ Policlinico-VittorioEmanuele University of Catania Cardiologia Department University of Catania Catania Italy 29Department of Medical Sciences and Uppsala Clinical Research Center UppsalaUniversity Senior Interventional Cardiologist Uppsala University Hospital Uppsala Sweden 30Centro Nacional de Investigaciones Cardiovasculares (CNIC) Melchor FernandezAlmagro Madrid Spain 31Department of Cardiology Hospital Universitario 12 de Octubre Madrid Spain 32Department of Cardiology Leiria Hospital Centre Portugal33Oberarzt Medizinische Klinik und Poliklinik I Ludwig-Maximilians-Universitat (LMU) Campus Groszlighadern Munchen Germany 34Department of Pharmacology Catholic UniversitySchool of Medicine Rome Italy 35Taipei Medical University Taipei Taıwan 36Cardiology Department University of Washington Seattle USA 37OU Heart Rhythm Institute OUHealth Sciences Center Oklahoma USA 38Instituto Nacional de Cardiologia I Chavez Electrofisiologia Mexico DF Mexico and 39Linmed Hospital Benoni South Africa

Received 25 June 2018 editorial decision 28 June 2018 accepted 28 June 2018

In 2014 a joint consensus document dealing with the management of antithrombotic therapy in atrial fibrillation(AF) patients presenting with acute coronary syndrome (ACS) andor undergoing percutaneous coronary or valveinterventions was published which represented an effort of the European Society of Cardiology Working Group onThrombosis European Heart Rhythm Association (EHRA) European Association of Percutaneous CardiovascularInterventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart RhythmSociety (HRS) and Asia-Pacific Heart Rhythm Society (APHRS) Since publication of this document additional datafrom observational cohorts randomized controlled trials and percutaneous interventions as well as new guidelineshave been published Moreover new drugs and devicesinterventions are also available with an increasing evidencebase The approach to managing AF has also evolved towards a more integrated or holistic approach In recognizingthese advances since the last consensus document EHRA WG Thrombosis EAPCI and ACCA with additionalcontributions from HRS APHRS Latin America Heart Rhythm Society (LAHRS) and Cardiac Arrhythmia Society ofSouthern Africa (CASSA) proposed a focused update to include the new data with the remit of comprehensivelyreviewing the available evidence and publishing a focused update consensus document on the management ofantithrombotic therapy in AF patients presenting with ACS andor undergoing percutaneous coronary or valveinterventions and providing up-to-date consensus recommendations for use in clinical practice

Keywords European Heart Rhythm Association bull Consensus document bull Position paper bull Atrial fibrillation bull Acutecoronary syndrome bull Coronary artery disease bull Myocardial infarction bull Percutaneous coronaryintervention bull Stent bull Antithrombotic therapy bull Antiplatelet agents bull Anticoagulation bull Vitamin Kantagonists bull Non-vitamin K antagonist oral anticoagulants bull Low molecular weight heparin bull Parenteralanticoagulants bull Left atrial appendage occlusion bull Stroke bull Thromboembolism bull Thrombosis bull Bleeding

Table of Contents

Introduction 3Evidence review 3

An overview of new data since last version of the document 3

Observational cohorts 3New randomized controlled trials on antithrombotic therapy 4

Oral anticoagulants 4Antiplatelet drugs 5Parenteral anticoagulants 7

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low thrombotic risk

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Expert consensus

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restarted

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specific NOAC

Expert consensus

Continued

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aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

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Introduction

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procedure

Consensus statement

instruction

Symbol

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applicable

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Antiplatelet drugs

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ESC 2017

update5

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and followup

106107113122

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Continued

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low thrombotic risk

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Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

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restarted

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specific NOAC

Expert consensus

Continued

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aspirin and OAC)

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Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

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with OAC alone

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aspirin and OAC)

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low bleeding risk

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Clopidogrel

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ownloaded from

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oma user on 05 N

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and followup

106107113122

130136137

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low thrombotic risk

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after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

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restarted

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specific NOAC

Expert consensus

Continued

ownloaded from

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oma user on 05 N

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aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

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low thrombotic risk

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after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

References

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

Mitral intervention

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ESC myocardial

revascularization

2017143

AF 20162

ACCAHA

2016 combined

OACAPT144

ESC 2017

update5

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullBe

(12ndash

ndash48

(30ndash

(70ndash

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

0ndash2

ndash70

ndash30

65ndash7

ithits

20ndash

65ndash7

to3ndash

ndash100

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullIn

20ndash

ndash70

bullLo

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

References

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

Mitral intervention

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ESC myocardial

revascularization

2017143

AF 20162

ACCAHA

2016 combined

OACAPT144

ESC 2017

update5

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullBe

(12ndash

ndash48

(30ndash

(70ndash

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

0ndash2

ndash70

ndash30

65ndash7

ithits

20ndash

65ndash7

to3ndash

ndash100

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullIn

20ndash

ndash70

bullLo

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

Mitral intervention

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ESC myocardial

revascularization

2017143

AF 20162

ACCAHA

2016 combined

OACAPT144

ESC 2017

update5

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullBe

(12ndash

ndash48

(30ndash

(70ndash

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

0ndash2

ndash70

ndash30

65ndash7

ithits

20ndash

65ndash7

to3ndash

ndash100

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullIn

20ndash

ndash70

bullLo

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ESC myocardial

revascularization

2017143

AF 20162

ACCAHA

2016 combined

OACAPT144

ESC 2017

update5

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullBe

(12ndash

ndash48

(30ndash

(70ndash

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

0ndash2

ndash70

ndash30

65ndash7

ithits

20ndash

65ndash7

to3ndash

ndash100

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullIn

20ndash

ndash70

bullLo

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ESC myocardial

revascularization

2017143

AF 20162

ACCAHA

2016 combined

OACAPT144

ESC 2017

update5

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullBe

(12ndash

ndash48

(30ndash

(70ndash

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

0ndash2

ndash70

ndash30

65ndash7

ithits

20ndash

65ndash7

to3ndash

ndash100

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullIn

20ndash

ndash70

bullLo

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

ESC myocardial

revascularization

2017143

AF 20162

ACCAHA

2016 combined

OACAPT144

ESC 2017

update5

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullBe

(12ndash

ndash48

(30ndash

(70ndash

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

0ndash2

ndash70

ndash30

65ndash7

ithits

20ndash

65ndash7

to3ndash

ndash100

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullIn

20ndash

ndash70

bullLo

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

bullBe

(12ndash

ndash48

(30ndash

(70ndash

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

0ndash2

ndash70

ndash30

65ndash7

ithits

20ndash

65ndash7

to3ndash

ndash100

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullIn

20ndash

ndash70

bullLo

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

0ndash2

ndash70

ndash30

65ndash7

ithits

20ndash

65ndash7

to3ndash

ndash100

limite

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

bullIn

20ndash

ndash70

bullLo

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

bullIn

20ndash

ndash70

bullLo

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

VKA NOAC

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

prevailing

OAC alone

Beyond12mo

1 mo Triple Therapy

Aspirin

Clopidogrel

prevailing

1 mo Triple Therapy

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

and followup

106107113122

130136137

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

low thrombotic risk

regimen

omy is not known

after PCIACS

Continued

Expert consensus

70) aimed for

anticoagulation

with OAC alone

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

restarted

Continued

specific NOAC

Expert consensus

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

aspirin and OAC)

ated with their use

Expert consensus

low bleeding risk

Continued

mgday)

Primary PCI

diated reperfusion

14ndash6

Continued

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

14ndash6

100 mgday)

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

ownloaded from

httpsacademicoupcom

oma user on 05 N

ovember 2018

euy174-TF2

euy174-TF3

euy174-TF1

euy174-TF4

euy174-TF5

euy174-TF6

Documents

Heart Rhythm Association (EHRA), European · 11/5/2018 · Institute of Clinical Medicine, University of Oslo, Oslo, Norway; 11Centre for Heart Rhythm Disorders, South Australian