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Antithrombotische Therapie bei ACS: Müssen
wir etwas ändern?
Prof. Dr. med. Dirk Sibbing
20. Oktober 2018
• Research grants: Roche Diagnostics, Daiichi Sankyo
• Speaker fees / Advisory board activities: Sanofi, Bayer,
Astra Zeneca, Pfizer, Daiichi Sankyo, Haemonetics, BMS
COI
20 Jahre DAPT Studien
35 Studien
>225,000
Patienten
ESC DAPT Guidelines, Valgimigli et al., EHJ 2017
2018 ESC Guidelines: Antithrombotika
BivalirudinDabigatranEnoxaparin UFH
ApixabanEdoxaban
Rivaroxaban
VKAs
Factor Xa
Thrombin
Fibrin
FibrinoganProthrombinCoagulation
cascadeTissu Factor
(Tissue lesion)
An
ticoagu
lant d
rug
Aspirin
DAPT
ClopidogrelPrasugrelTicagrelorCangrelor
An
tiplatelet d
rug
GPIIb/IIIaactivation
TxA2
ADP
GPIIb/IIIa Inhibitors(Abciximab,Eptifibatide,
Tirofiban)
Glycoprotein IIb/IIIa receptor
Soluble mediators (ADP, TxA2)
Clot-bound thrombin/FXa
2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018
Agenda
1) Was sind die aktuellen Empfehlungen
zur dualen Plättchenhemmung bei ACS
Patienten ?
2) Strategien zur Individualisierung der
Plättchenhemmung in 2018: Länger?
Kürzer? De-Eskalation?
Agenda
1) Was sind die aktuellen Empfehlungen
zur dualen Plättchenhemmung bei ACS
Patienten ?
2) Strategien zur Individualisierung der
Plättchenhemmung in 2018: Länger?
Kürzer? De-Eskalation?
2018 ESC Guidelines
2018 ESC/EACTS Guidelines on myocardial revascularisationEuropean Heart Journal (2018) 00, 1-96 - doi:10.1093/eurheartj/ehy394
www.escardio.org/guidelineswww.escardio.org/guidelines
2018 ESC/EACTS Guidelines on myocardial revascularization
2
Authors/Task Force Members: Franz-Josef Neumann (ESC Chairperson) (Germany),Miguel Sousa-Uva (EACTS Chairperson) (Portugal), Anders Ahlsson (Sweden),Fernando Alfonso (Spain), Adrian P. Banning (UK), Umberto Benedetto (UK),Robert A. Byrne (Germany), Jean-Philippe Collet (France), Volkmar Falk (Germany),Stuart J. Head (The Netherlands), Peter Jüni (Canada), Adnan Kastrati (Germany),Akos Koller (Hungary), Steen D. Kristensen (Denmark), Josef Niebauer (Austria),Dimitrios J. Richter (Greece), Petar M. Seferovic (Serbia), Dirk Sibbing (Germany),Giulio G. Stefanini (Italy), Stephan Windecker (Switzerland), Rashmi Yadav (UK),Michael O. Zembala (Poland).
The Task Force on myocardial revascularization of the European Society of Cardiology (ESC)and European Association for Cardio-Thoracic Surgery (EACTS).
Developed with the special contribution of the European Association for Percutaneous Cardiovascular Interventions (EAPCI).
Aktuelle ESC 2018 Leitlinie
Recommendations Class Level
Pre-treatment and antiplatelet therapy
Aspirin is recommended for all patients without contraindications at an
initial oral loading dose of 150-300 mg (or 75-250 mg i.v.), and at a
maintenance dose of 75-100 mg daily long-term.
I A
A P2Y12 inhibitor is recommended in addition to aspirin, maintained over
12 months unless there are contraindications such as an excessive risk
of bleeding. Options are:
I A
• Prasugrel in P2Y12-inhibitor naïve patients who proceed to PCI
(60 mg loading dose, 10 mg daily dose). I B
• Ticagrelor irrespective of the preceding P2Y12 inhibitor regimen
(180 mg loading dose, 90 mg b.i.d.). I B
2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018
• Clopidogrel (600 mg loading dose, 75 mg daily dose) only when prasugrel or ticagrelor are not available or are contraindicated.
I B
DAPT Dauer: NSTEMI
2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018
Antithrombotic Treatment in Patients Undergoing Percutaneous Coronary Intervention
NSTE-ACSTreatment Indication
(Pre-) Treatment DAPT
Time
1 month
3 months
6 months
12 months
30 months
36 months
DA
PT
Du
rati
on
A T C
High Bleeding Risk
No Yes
12 months DAPT
A C
A P
A Tor
or
A T
A P A C
or
DAPT >12 months
A T
orA C
6 months DAPT A
T
C
P
Antiplatelet drugs :
Aspirin
Clopidogrel
Prasugrel
Ticagrelor
DAPT Dauer: STEMI
2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018
Antithrombotic Treatment in Patients Undergoing Percutaneous Coronary Intervention
STEMITreatment Indication
(Pre-) Treatment DAPT
Time
1 month
3 months
6 months
12 months
30 months
36 months
DA
PT
Du
rati
on
A T P C
No Yes
12 months DAPT
A C
A P
A Tor
or
A T
A P A C
or
DAPT >12 months
A T
orA C
6 months DAPT
High Bleeding Risk
A
T
C
P
Antiplatelet drugs :
Aspirin
Clopidogrel
Prasugrel
Ticagrelor
Triple: Was? Wielange?
2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018
NOACs & Triple
2018 ESC/EACTS Guidelines on myocardial revascularisationEuropean Heart Journal (2018) 00, 1-96 - doi:10.1093/eurheartj/ehy394
www.escardio.org/guidelineswww.escardio.org/guidelines
Dual antiplatelet therapy duration in patients with indication for oral anticoagulation
20
Recommendations Class Level
Dual therapy with clopidogrel 75 mg/day and an OAC should be considered as an alternative to 1-month triple antithrombotic therapy in patients in whom the bleeding risk outweighs the ischaemic risk.
IIa A
In patients with non-valvular AF requiring anticoagulation and antiplatelet treatment, a NOAC should be preferred over VKAs. IIa A
In patients with an indication for a VKA in combination with aspirin and/or clopidogrel, the dose intensity of the VKA should be care-fully regulated with a target INR in the lower part of the re-commended target range and time in the therapeutic range >65%.
IIa B
Discontinuation of antiplatelet treatment in patients treated withOAC should be considered at 12 months. IIa B
NEW:
PIONNER
RE-DUAL
Agenda
1) Was sind die aktuellen Empfehlungen
zur dualen Plättchenhemmung bei ACS
Patienten ?
2) Strategien zur Individualisierung der
Plättchenhemmung in 2018: Länger?
Kürzer? De-Eskalation?
Scores
2017 ESC/EACTS DAPT Guidelines, EHJ 2017
DAPT Eskalation
• GRAVITAS
• TRIGGER-PCI
• ARCTIC
Kein Benefit einer „Guided* Eskalation“
Price et al., JAMA 2011, Trenk et al., JACC 2012, Collet et al., NEJM 2012
*Guided = gesteuert durch Plättchenfunktionstestung
Prasugrel: Ischämien vs.
Blutungen
Antman et al., JACC 2009, Wiviott et al., NEJM 2007
Akute Phase Chronische Phase
Defi
nit
e S
T
Becker et al., EHJ 2011; Velders et al., Heart 2016
Ticagrelor: Ischämien vs.
Blutungen
PLATO
Real-World Daten zu DAPT De-Eskalation (Switching)
15 % 28 % DAPT De-Eskalation
Zettler et al., AHJ 2017
Cuisset et al., EHJ 2017
PR
O
TOPIC Studie
De Luca et al., Eurointervention 2017
CO
NT
RA
SCOPE Register
Clopidogrel: Wirkung & Outcome
Gurbel et al., Circulation 2003 Aradi, …, Sibbing, EHJ 2015
Plattchenfunktionstestung (PFT) als “Tool” um eine DAPT De-Eskalation
sicherer zu machen
20,839 Patienten
Patienten & Studienarme
Biomarker
positive ACS
patients
(n=2610) with
successful
PCI
7 days
clopidogrel
7 days
prasugrel
14 days prasugrel
11 ½ months
prasugrel
11 ½ months
clopidogrel
PF
T (
Mu
ltip
late
an
aly
ser)
@ 2
weeks a
fter
dis
ch
arg
e
Low
Responders
(40%)
Good
Responders
(60%)
Follow-up:
Guided de-escalation
(n=1304)
11 ½ months
prasugrel
Ho
sp
ita
l d
isc
ha
rge
Control
(n=1306)
98%
@ 2 weeks
96%
@ 12 months
Dec 2013 –
May 2016
R*
1:1
unchanged
therapy
Ad
he
ren
ce
to
tre
atm
en
t:
>9
4%
in
bo
th g
rou
ps
Sibbing et al., Lancet 2017
Primärer Studienendpunkt
0
2
4
6
8
10
0 60 120 180 240 300 360 (days)
HR 0·81 (0·62-1·06)
p=0·0004 for non-inferiority
(p=0·1202 for superiority)
(CVD, MI, stroke, BARC ≥2)
-- Control group
-- Guided de-escalation group
No. at risk Control
De-escalation 1306
1304
1238
1234
1220
1213 1190
1189
1132
1129 1124
1124
924
942
9·0%
7·3%
Eve
nt p
rob
ab
ility
(%
)
Sibbing et al., Lancet 2017
Blutungen (BARC 1-5)
Sekundäre Studienendpunkt
(CV
D,
MI, s
troke
)
Ischämien
Sibbing et al., Lancet 2017
PEGASUS: Primärer
Endpunkt
Bonaca et al., NEJM 2015
ARR: 1.2% RRR: 15% NNT: 84
PEGASUS: Blutungen
Bonaca et al., NEJM 2015
PEGASUS: Mehrgefäß-KHK
Bansilal et al., JACC 2018
DAPT Alternativen in 2018
2018 ESC/EACTS guidelines on myocardial revascularization, EHJ 2018
Recommendations Clas
s Leve
l
De-escalation of P2Y12 inhibitor treatment (e.g. with a switch from prasugrel or ticagrelor to clopidogrel) guided by platelet function testing may be considered as an alternative DAPT strategy, especially for ACS patients deemed unsuitable for 12-month potent platelet inhibition.
IIb B
In patients with ACS who have tolerated DAPT without a bleeding complication, continuation of DAPT for longer than 12 months may be considered.
IIb A
∑: Alternative DAPT Strategien zur DAPT Eskalation und De-eskalation
PEGASUS DAPT
TROPICAL-ACS TOPIC
Zusammenfassung
• Standards zur Plättchenhemmung nach ESC Leitlinie sind eine 12 monatige DAPT Dauer mit ASS + Prasugrel oder Ticagrelor und eine 6 monatige DAPT Dauer bei hohem Blutungsrisiko
• Alternative Strategien und DAPT Optionen sind
a) eine verlängerte DAPT Dauer mit potenten Plättchenhemmern wenn das Ischämierisiko überwiegt
b) sowie eine verkürzte DAPT Dauer oder eine DAPT De-Eskalation bei hohem Blutungsrisiko oder aus sozio-ökonomischer Indikation
• Aktuelle Leitlinien unterstützen eine individualisierte Therapie in
ausgewählten Fällen und insb. i.R. einer DAPT De-Eskalation
Vielen Dank für die
Aufmerksamkeit!
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