Rocking the boat on Rivaroxaban
Rocking the boat on Rivaroxaban. Manish Khullar, BSc Pharm Interior Health Pharmacy Resident August 15, 2013. Learning Objectives. Describe the risk assessment of stroke for atrial fibrillation List therapeutic alternatives for stroke prevention - PowerPoint PPT Presentation
Slide 1Rocking the boat on RivaroxabanManish Khullar, BSc PharmInterior Health Pharmacy ResidentAugust 15, 2013Learning ObjectivesDescribe the risk assessment of stroke for atrial fibrillation List therapeutic alternatives for stroke prevention Explain the role of rivaroxaban in patients with atrial fibrillation and aortic valve replacement2Our PatientIDA 74 year old male admitted to the CTU on August 6th, 2013CC/HPIShortness of breath for 3 days that has been getting progressively worseFatigue/weaknessMild non-productive cough AllergiesNo known drug allergiesSocial HistoryLives at home with spouseNo alcoholQuit smoking 40 years ago Anticoagulant historyDiagnosed with atrial fibrillation this year and placed on warfarin (INR 2-3) 2 months ago Was on warfarin for 1 month but did not tolerate side effects (insomnia, headaches, vomiting) GP switched him to rivaroxaban last month and has been on it since admission Our PatientPast Medical HistoryMedications Prior to AdmissionCongestive Heart FailureCarvedilol 25 mg po BIDValsartan 80mg po dailyFurosemide 20mg po dailyAtrial Fibrillation Rivaroxaban 20mg po daily Carvedilol 25mg po BIDSecondary prevention MICarvedilol 25 mg po BIDValsartan 80mg po dailyAtorvastatin 40mg po daily AVR (bioprosthetic)Rivaroxaban 20mg po daily Ventricular tachycardia ICD implantAmiodarone 200mg po dailyType 2 diabetesMetformin 500mg po TIDOur PatientPast Medical HistoryMedications Prior to AdmissionHypertensionCarvedilol 25 mg po BIDValsartan 80mg po dailySecondary Prevention of StrokeRivaroxaban 20mg po dailyAtorvastatin 40mg po daily Dyslipidemia Atorvastatin 40mg po dailyCKD Valsartan 80mg po daily DepressionEscitalopram 20mg po dailyOsteoarthritis (left hip) Acetaminophen 1 gram po daily prn Review of SystemsVitalsT: 36.7 BP: 94/62 HR: 92 RR: 20 SaO2: 95% RACNSGCS X 15, A+O x 3 HEENTNormal RESPShortness of breath upon moving Wheezes when laying downDecreased breath sounds left lung crackles on right lung Non-productive coughCVSJVP >3cm ASA, pedal edema, CHADS2: 5GIDistended abdomenGUSrCr: 206 (baseline SrCr 156) eGFR: 28 MSK/DERMPedal edema ENDOHEMEHg: 86 MCV: 82.4 Plt: 209 INR: 3.7 WBC: 7.9 Neuts: 6.6 LYTESNa: 131 K: 4.9 Cl: 98 InvestigationsDiagnostics:Chest x-ray (upon admission):Left sided pleural effusionMild right sided pleural effusionECHO: PendingEjection fraction from Jan 2013: 40-45% EndoscopyPending Current Problems and Medications CHFCarvedilol 25 mg po BIDFurosemide 60mg po dailyAnemiaNoneAcute onchronic renal failureNoneType 2 diabetesMetformin 250mg po TIDAortic valve replacementNoneMI- 2o preventionAtorvastatin 40 mg po dailyCarvedilol 25 mg po BIDAtrial fibrillationAmiodarone 20mg po dailyCKDNone Depression Escitalopram 20mg po dailyOsteoarthritis (left hip)Acetaminophen+caffeine+ codeine 2 tablets po HS 9Course in HospitalAdmitted to investigate shortness of breath and worsening CHFEndoscopy identified gastric ulcer Transfused with 2 units of blood List of DRPsJF is at risk of stroke secondary to not receiving any anticoagulation therapy for his atrial fibrillation and would benefit from reassessment of his stroke prophylaxis therapy.JF is at risk of stroke secondary to not receiving antithrombotic therapy with AVR and would benefit from reassessment of his stroke prophylaxis therapy. JF is at risk of death and hospitalizations secondary to receiving too low dose of atorvastatin despite his high risk and would benefit from reassessment from his prophylaxis therapy. JF is at risk of death and hospitalizations secondary to not receiving an ACE inhibitor or ARB for MI prophylaxis and would benefit from reassessment of therapy. just say he has number of DRPS like risk of stroke, risk of CHFdont read them word for word 11List of DRPsJF is at risk of death and hospitalizations secondary to not receiving antiplatelet therapy for post-MI and would benefit from reassessment of therapy. JF is at risk of death and hospitalizations secondary to not receiving an ACE inhibitor or ARB despite having congestive heart failure and would benefit from reassessment of his congestive heart failure therapy.JF is at risk of experiencing adverse effects of metformin secondary to being on metformin despite poor renal function and would benefit from reassessment of his therapy. JF is at an increased risk of bleeding, stroke/death due to unclear efficacy in rivaroxaban in AVR patients and would benefit from reassessment of therapy. DRP FocusJF is at risk of stroke secondary to not receiving any anticoagulation therapy for his atrial fibrillation and would benefit from reassessment of his stroke prophylaxis therapy.JF is at risk of stroke secondary to not receiving antithrombotic therapy with AVR and would benefit from reassessment of his stroke prophylaxis therapy. JF is at an increased risk of bleeding, stroke/death due to unclear efficacy in rivaroxaban in AVR patients and would benefit from reassessment of therapy.BackgroundStroke occurs in atrial fibrillation due to blood stasis in atria leading to clot formation inside the chambersUpon cardioversion to NSR, the clot may eject and stroke can occurAssessing Risk of Stroke in Atrial Fibrillation Stroke assessment tool: CHADS2 CHADS2 Score Stroke Risk/year01.9%12.8%24%35.9%48.5%512.5%618.2 %CHADS2VASc-same as CHADS2 but incorporates vascular disease (MI, PAD, aortic plaques) , age 65-74 and sex (female) 15Need for Antithrombotics in AVRPatients with prosthetic valves are at risk of thromboembolic complications (stroke, valve obstruction and/or regurgitation)Risk is higher with mechanical valves than with bioprosthetic valvesRisk is higher with mitral than aortic prosthetic valves Making antithrombotic therapy necessary in these patients The risk also is increased in the presence of concomitant risk factors for thromboembolism, including:-atrial fibrillation-LV dysfunction16Goals of TherapyReduce mortalityReduce morbidity (strokes, hospitalizations)Prevent adverse eventsImprove quality of life Antithrombotic Alternatives for AVRCHEST guidelines:in patients with aortic bioprosthetic valves, who are in sinus rhythm, and have no other indication for VKA therapy, we recommend ASA (50-100mg/d) CHEST 200818Antithrombotic Alternatives for AVRCHEST guidelines:in patients with bioprosthetic valves who have additional risk factors for thromboembolism, including AF, hypercoaguable state or low ejection fraction, we recommend VKA therapy (target INR 2-3)low dose aspirin should be considered, particularly in patients with history of atherosclerotic vascular disease. We suggest ASA not be added to long-term VKA therapy in patients with bioprosthetic heart valves who are at particularly high risk of bleeding CHEST 200819Therapeutic Alternatives for Atrial FibrillationAspirinAspirin + ClopidogrelWarfarinDabigatranRivaroxabanApixabansay based on these this prompted my clinical questions say that since guidelines say use warfarin with other clinical indications this is what prompted my quesTalk about patients CHADS220Clinical Question In a 74 year old patient who is at high risk of ischemic stroke secondary to atrial fibrillation and bioprosthetic aortic valve replacement, is rivaroxaban as compared to warfarin, effective at reducing stroke risk without increasing risk of bleeding? Literature ReviewDatabasesPubmed, medline, google scholar Search TermsWarfarin, atrial fibrillation, rivaroxaban, stroke, aortic valve replacementLimitsmeta-analysesRCTs, english, humanResults 0 trials DatabasesPubmed, medline, google scholar Search TermsRivaroxaban, atrial fibrillation, stroke Limitsmeta-analysesRCTs, english, humanResults 1 RCTCouldnt find any evidence in these patients so I had to broaden my search etc 22ROCKET-AFDesignRandomized, multicenter, double blind, double-dummy, non-inferiority trialPopulationAtrial fibrillation, age > 18, CHADS2 > 2 Excluded patients with prosthetic heart valvesAt baseline:(n=14, 264) median age 73 years old, male 60%, 90% with CHADS2 > 2 (mean 3.48), CrCl 67Prior CVA (~55%), HF (~63%), HTN (~90%), DM (~40%), MI (~16.6%), PVD (~5%), COPD (~11%)BB (65%), diuretic (60%), ACEI (55%), statin (43%), digitalis (39%), aspirin (38%) InterventionRivaroxaban 20mg po daily or 15mg po daily if CrCl 30-49mL/min vs dose-adjusted warfarin (INR 2-3) Primary OutcomeComposite of stroke and systemic embolism Composite of major and clinically relevant nonmajor bleedingROCKET-AF. NEJM 2011;10.1056/NEJMoa1009638-Stroke was defined as an acute, focal neurologic deficit of presumed cerebrovascular etiology that persisted beyond 24 hours (if 20g/L, transfusion of 2 units of whole blood or packed red cells or permanent disability-Clinically relevant bleed criteria did not meet for major bleed but reqd necessitated medical treatment, unplanned medical attention, or temporary interruption of the study drug23Results: Efficacy RivaroxabanWarfarinHazard Ratio (95% CI) p-value Patients(n) Events (n) Event rate/100 patient yearsPatients(n) Events (n) Event rate/100 patient yearsRivaroxaban vs warfarinNoninfe-riority69581881.770042412.2 0.79 (0.66-0.96) 1) -Less effective than other agents and same bleed risk as Warfarin-Patient didnt tolerate warfarin -Patient doesnt want to go for INR testing-Indicated for A. fib-Shown to be harmful in those with mechanical valves-Renal failure -Twice daily -Expensive-Indicated for A.fib-No evidence/studies and harm suggested with similar agent-Once daily-Expensive-Indicated for A. fib-Twice daily-Expensivehttp://www.sparctool.com/Use NESA to weed out my choices Major Bleeding: Definition varies from trial to trial, but generally includes bleeding requiring hospitalization, gastrointestinal bleeding, intracranialhemorrhage, hemorrhage associated with >20 g/L drop in HgB, bleeding requiring transfusion of two or more units of blood, any intraocular,retroperitoneal, or intraarticular bleeding.27Assessment of Therapeutic Alternatives for AVRASAASA + ClopidogrelWarfarinDabigatranRivaroxabanApixabanStroke Reduction--Studied in mechanical valves --Bleed RiskIncreased harm (RE-ALIGN) 28Therapeutic Recommendation and JustificationDo not restart rivaroxaban for stroke prophylaxisSuggest starting warfarin at a low dose such as 3mg po daily to target INR 2-3 once clinically stable and active bleeding ruled out1) Not studied in aortic valve replacement; Suggestion of harm with other new anticoagulants (dabigatran) in patients with valve replacement; renal impairment 2) Given high stroke risk and presence of bioprosthetic valve, the patient may benefit from warfarin; likely still has rivaroxaban in the body due to its prolonged half-life in renal impaired patients (normal is 10-15 hours so probably even longer in him) 29Monitoring: EfficacyS: dizziness, blurred vision, numbness, paralaysis or weakness, fatigue, shortness of breath O: loss of coordination, slurred speechMonitoring: SafetyS: Dizziness, fatigue, headache, lethargy, GI upset, abdominal pain, O: vitals, Hgb, MCV, INR, AST, ALT, rash, urticaria, bruisingFollow-upAugust 12:Discussed pros and cons of warfarin therapy with patientAfter learning more about the drug and importance of INR monitoring and interactions, the patient and his family were amenable to trying warfarin againInitiated warfarin 3mg po daily with daily INRs Questions?