The Poor Long-Term Candidate for Warfarin: NOAC or Left Atrial Appendage Closure?

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1 The Poor Long-Term Candidate for Warfarin: NOAC or Left Atrial Appendage Closure? Suneet Mittal, MD, FACC, FHRS Director, Electrophysiology Laboratory Valley Health System Ridgewood, NJ and New York, NY May 14, 2016 Disclosures: Consultant to Boston Scientific, SentreHeart

2 Professional Society Recommendations Published online August 29, 2014

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4 Although this population constitutes a small minority of LAA occlusion recipients today, this is the only indication that is currently based on randomized controlled data

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6 What About NOACs? Retrospective analysis of administrative claims data (privately insured and Medicare Advantage enrollees) Patients (n=64,661) with atrial fibrillation who initiated treatment with warfarin, dabigatran, rivaroxaban, or apixaban between November 1, 2010 and December 31, 2014 were identified Endpoint: adherence 80% Yao X et al. J Am Heart Assoc 2016 doi: /jaha

7 Yao X et al. J Am Heart Assoc 2016 doi: /jaha

8 Patients with a high thrombo-embolic risk (CHA 2 DS 2 -VASc score > 2) but contraindication to oral and systemic anticoagulation (e.g., history of a significant bleeding event such as intracranial or life threatening bleeding, the source of which cannot be eliminated) represent the most accepted clinical indication for LAA occlusion

9 Higher rate of total bleeding in DAFT arm as compared with warfarin Trends towards high rate of major and severe bleeding in DAFT arm Lancet 2006; 367:

10 US FDA Approved Indication This device is indicated to reduce the risk of thromboembolism from the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation who: Are at increased risk for stroke and systemic embolism based on CHADS 2 or CHA 2 DS 2 -VASc scores and are recommended for anticoagulation; Are deemed by their physicians to be suitable for warfarin; and Have an appropriate rationale to seek a nonpharmacologic alternative to warfarin, taking into account the safety and effectiveness of the device compared to warfarin. (March 13, 2015)

11 CMS Approved Indication This device is indicated to reduce the risk of thromboembolism from the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation who: A CHADS 2 score 2 or CHA 2 DS 2 -VASc score 3 A formal shared decision making interaction with an independent non-interventional physician using an evidence-based decision tool on oral anticoagulation in patients with NVAF prior to LAAC. A suitability for short-term warfarin but deemed unable to take long term oral anticoagulation following the conclusion of shared decision making, as LAAC is only covered as a second line therapy to oral anticoagulants. Decision memo: CAG-00445N (March 13, 2015)

12 CMS Approved Indication This device is indicated to reduce the risk of thromboembolism from the left atrial appendage (LAA) in patients with non-valvular atrial fibrillation who: A CHADS 2 score 2 or CHA 2 DS 2 -VASc score 3 A formal shared decision making interaction with an independent non-interventional physician using an evidence-based decision tool on oral anticoagulation in patients with NVAF prior to LAAC. A suitability for short-term warfarin but deemed unable to take long term oral anticoagulation following the conclusion of shared decision making, as LAAC is only covered as a second line therapy to oral anticoagulants. Decision memo: CAG-00445N (March 13, 2015)

13 HAS-BLED Score H: hypertension A: abnormal renal/liver function S: stroke B: bleeding history L: labile INR E: elderly D: drug consumption/alcohol abuse Danish cohort of 118,584 patients with non-valvular AF 1-year bleeding rate on VKA 0-1: 2.66% (95% CI: ) 2: 5.54% (95% CI: ) 3: 8.11% (95% CI: ) Olesen JB et al. J Thromb Haemost 2011; 9:

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15 The Perils of Triple Therapy Dewilde WJM et al. Lancet 2013; 381: Lamberts M et al. JACC 2013; 62:

16 The Perils of Triple Therapy ISAR-TRIPLE Fiedler KA et al. Am Heart J 2014; 162: e1

17 The Perils of Triple Therapy ISAR-TRIPLE (DES stents) BARC Types 1 to 5 Bleeding Composite Ischemic Endpoints Fiedler KA et al. JACC 2015; 65:

18 Unanswered Questions What about the use of ticagrelor or prasugrel instead of clopidogel? Limited data for prasugrel (n=21) No data for ticagrelor Sarafoff et al. JACC 2013; 61:

19 Unanswered Questions What about the use of ticagrelor or prasugrel instead of clopidogel? What about the use of NOACs instead of VKAs? Data from patients undergoing PCI

20 NOACs + DAPT Post-PCI ATLAS ACS 2 TIMI 51 (N Engl J Med 2012; 366:9-19) Rivaroxaban associated with Increased rates of major bleeding not related to coronary-artery bypass grafting (2.1% vs. 0.6%, P<0.001) Increased rates of intracranial hemorrhage (0.6% vs. 0.2%, P=0.009) No significant increase in fatal bleeding (0.3% vs. 0.2%, P=0.66) APPRAISE-2 (N Engl J Med 2011; 365: ) Apixaban associated with Increased major bleeding (1.3% vs. 0.5%, P=0.001) A greater number of intracranial and fatal bleeding events RE-DEEM (Eur Heart J 2011; 32: ) Dabigatran associated with Dose dependent increase in, the composite of major or clinically relevant minor bleeding events (3.5, 4.3, 7.9, and 7.8% in the respective 50, 75, 110, and 150 mg dabigatran groups, compared with 2.2% in the placebo group, P< 0.001)

21 Ongoing Studies PIONEER-AF-PCI Gibson CM et al. Am Heart J 2015; 169: e5

22 Ongoing Studies REDUAL PCI (NCT ) Compare the following protocols in patients with atrial fibrillation undergoing a PCI with stenting (elective or due to ACS) 110 mg bid dabigatran + clopidogrel or ticagrelor 150 mg bid dabigatran +clopidogrel or ticagrelor warfarin (INR 2-3) + clopidogrel or ticagrelor + aspirin <= 100mg qd

23 Conclusions Although the Watchman left atrial appendage closure is now available, there are important differences between the types of patients that were enrolled in the clinical trials that led to device approval and recommendations from professional societies, labeling per the US FDA, and CMS requirements for payment coverage NOACs alone are unlikely to be the answer for many patients Low rates of adherence over time High risk of embolic events in non-adherent patients with elevated CHA 2 DS 2 -VASc scores Need to be very careful utilizing the device in patients with absolute contraindications to even short-term warfarin Registry and randomized trial data needed DAPT by itself not necessarily a low-risk alternative A big opportunity may be in patients with elevated HAS-BLED score and those that would otherwise be exposed to triple therapy