Speaker disclosure § Abbott – consultant (minor) Updates in AF Cara Pellegrini, MD Acting Chief of Cardiology, SFVA Associate Professor of Medicine, UCSF May 22, 2017 Discussion topics Case #1 RS is an 78 yo M with new persistent AF, h/o HTN, mild LV § How does one choose the right drug for stroke prevention in AF? dysfunction, PVD, anemia, and gout. Which stroke prevention strategy would you suggest? § How worried should I be about availability of reversal agents A. Aspirin § What about non-pharmacologic stroke prevention? B. Warfarin C. Dabigatran § When should you refer your patient for consideration of AF ablation, and how can you predict success? D. Rivaroxaban E. Apixaban § Should we be advocating lifestyle changes for AF? F. Edoxaban G. Aspirin and Clopidogrel
Case #1 CHA 2 DS 2 -VASc Score RS is an 78 yo M with new persistent AF, h/o HTN, mild LV Risk factor Score dysfunction, PVD, anemia, and gout. Which stroke Congestive heart failure / LV dysfunction 1 prevention strategy would you suggest? Hypertension 1 Age ≥ 75 2 A. Aspirin Diabetes mellitus 1 Stroke / TIA / thrombo-embolism 2 B. Warfarin Vascular disease 1 C. Dabigatran Age 65-74 1 D. Rivaroxaban Female 1 E. Apixaban CHA 2 DS 2 -VASc Score 4 F. Edoxaban G. Aspirin and Clopidogrel Annual Risk of Stroke or Systemic Embolism HAS-BLED Score 10-year follow-up rates among 73,538 of “real world” patients in the Risk factor Score Danish National Patient Registry Uncontrolled hypertension 1 who have nonvalvular AF and were Significant renal dysfunction 1 not treated with warfarin. Significant liver disease 1 Previous stroke 1 History of / predisposition to bleeding 1 Labile INRs 1 Age > 65 1 Antiplatelet / NSAID use 1 ≥ 8 alcoholic drinks / week 1 HAS-BLED Score 2 Olesen JB and colleagues, BMJ 2011
Annual Risk (%/yr) of Major Bleeding Relative Risk of Stroke or Systemic Embolism Associated with Oral Anticoagulants and Antiplatelet Major bleeding: bleeding requiring Drugs hospitalization, causing ↓ hemoglobin > 2 g/L, requiring transfusion. Olesen JB and colleagues, BMJ 2011 LaHaye SA and colleagues, European Heart Journal 2012 Relative Risk of Major Bleeding Associated with Treatment Recommendation Oral Anticoagulants and Antiplatelet Drugs (Lowest Attributable Net Risk) LaHaye SA and colleagues, European Heart Journal 2012 LaHaye SA and colleagues, European Heart Journal 2012
Validation table for CHA 2 DS 2 VASc Score = 4, Phone apps: HAS-BLED score = 2 Afib CDA + SPARCtool.com LaHaye SA and colleagues, European Heart Journal 2012 Phone app: SPARCtool.com Meta-Analysis of NOAC RCTs Stroke or systemic embolism Major bleeding Ruff CT and colleagues, The Lancet 2014
Meta-Analysis of NOAC RCTs Subgroup Analysis Secondary efficacy and safety outcomes Ruff CT and colleagues, The Lancet 2014 Ruff CT and colleagues, The Lancet 2014 Recommendations for Pharmacologic Stroke Prevention Subgroup Analysis § Aspirin (low efficacy) § Warfarin (low cost) § Dabigatran (lowest stroke risk) § Rivaroxaban (once daily dosing) § Edoxaban (once daily dosing, CrCl ≤ 95 ml/min) § Apixaban (lowest net risk) § Aspirin + Clopidogrel (modest efficacy, high bleeding risk) Interactions with medications, diet, patient preferences, monitoring Ruff CT and colleagues, The Lancet 2014 requirements, renal failure
Resources Case #2 HW is a 67 yo F with HTN and new paroxysmal AF. § Online AF clinical decision aid: She is very concerned about potential bleeding and the • http://www.afib.ca/ need for a reversal agent. Which agent has the worst outcome if bleeding occurs? § Mobile apps: • AFib CDA A. Warfarin • http://SPARCtool.com/ B. Dabigatran C. Rivaroxaban D. Apixaban § American College of Cardiology E. Edoxaban • http://www.teamanticoag.com/ Case #2 Observation outcomes after major bleeding In-hospital mortality significantly lower following DOAC bleeding: 9.8% vs 15.2 % HW is a 67 yo F with HTN and new paroxysmal AF. 30 day mortality trended lower: 12.6% vs. 16.3% She is very concerned about potential bleeding and the need for a reversal agent. Which agent has the worst Warfarin outcome if bleeding occurs? A. Warfarin DOAC B. Dabigatran C. Rivaroxaban D. Apixaban E. Edoxaban Time following index hospitalization (days) Xu Y and colleagues, Chest 2017
Dabigatran Rivaroxaban Apixaban Edoxaban Causes of Death in AF (Pradaxa) (Xarelto) (Eliquis) (Savaysa) Drug class Direct thrombin Factor Xa Factor Xa Factor Xa inhibitor inhibitor inhibitor inhibitor Efficacy vs. Superior Non-inferior Superior Non-inferior warfarin Major bleeding Similar Similar Reduced Reduced vs. warfarin Reversal agents Idarucizumab Andexanet alfa, Andexanet alfa, Andexanet alfa, (Praxbind), ciraparantag ciraparantag ciraparantag ciraparantag Elimination half- 12-17 5-9 young 12 10-14 life (hrs) 11-13 elderly Renal dosing Avoid CrCl < 15 Avoid CrCl < 15 Approved for Avoid CrCl or HD or HD HD patients > 95, < 15, HD Hepatic dose OK in liver Avoid in Child- Avoid in Child- Avoid in Child- adjustments disease Pugh B Pugh C Pugh B Avoid combo / Dronedarone* Phenytoin Phenytoin decrease dose* Gómez-Outes A and colleagues, JACC 2016 Declining stroke risk after AF episode Declining stroke risk after AF episode • 83% no AF in 120 days prior to stroke • Almost 25% had h/o AF, but no AF pre-stroke -> Poor Sensitivity Turakhia MP and colleagues, Circ Arrhythm Electrophysiol 2015 Turakhia MP and colleagues, Circ Arrhythm Electrophysiol 2015
Future Directions: Targeted Therapy Case #3 MF is an 80 yo M with PAF who has a h/o HTN, DM, a TIA, and • Prn anti-coagulation PUD s/p GIB while on warfarin. How can his risk of subsequent • Guided by actual thromboembolic event best be minimized? arrhythmia burden A. Warfarin plus PPI B. Apixaban C. Aspirin and clopidogrel D. Intervention on the left atrial appendage Passman R and colleagues, J Cardiovasc Electrophysiol 2016 Case #3 Watchman • Self-expanding nitinol frame covered by fabric MF is an 80 yo M with PAF who has a h/o HTN, DM, a TIA, and • Short-term anticoagulation recommended PUD s/p GIB while on warfarin. How can his risk of subsequent • FDA approved! thromboembolic event best be minimized? A. Warfarin plus PPI B. Apixaban C. Aspirin and clopidogrel D. Intervention on the left atrial appendage Jain AK and colleagues, Heart 2011
Watchman Data Meta-Analysis: Watchman vs. Warfarin § 2 RCTs (1261 pts) + 2 registries (1145 pts) Decreased: Increased: § Non-inferior to warfarin (mostly) § Hemorrhagic strokes § Ischemic strokes § Provider experience important No difference in all stroke or systemic embolism • Complication rate: 7.7% -> 2.2% § 99% off warfarin within a year § NOAC comparisons not yet done Holmes DR and colleagues, JACC 2015 Meta-Analysis: Watchman vs. Warfarin Meta-Analysis: Watchman vs. Warfarin Decreased: Decreased: Increased: § CV / unexplained death § Nonprocedural bleeding § Procedural bleeding No difference in major bleeding Trend toward decrease in all-cause death Holmes DR and colleagues, JACC 2015 Holmes DR and colleagues, JACC 2015
Meta-Analysis: Watchman vs. Warfarin Amplatzer cardiac plug (ACP) Decreased: Increased: § Hemorrhagic strokes § Ischemic strokes § CV / unexplained death § Procedural bleeding § Nonprocedural bleeding • Nitinol only, barbs to increase stability • High deployment success • Low stroke/embolism rate • 16% peri-device leak at 6 mo f/u • No real trial data • Not approved in US; approved in Europe Holmes DR and colleagues, JACC 2015 Jain AK and colleagues, Heart 2011; Urena M and colleagues, JACC 2013 LARIAT snare Thoracoscopic stand-alone left atrial appendectomy § Percutaneous ligation of LAA § Limited short-term results favorable § Painful § Complicated § Risky? • Well-established as part of cardiac surgery § Available in the US via • Very limited data on 510(K) approval process stand-alone procedure • Surgery! Ohtsuka T and colleagues, JACC 2013 Chatterjee S and colleagues, Ann Thorac Surg 2011
True anticoagulation alternative? Recommendation § 150 pt Watchman (ASAP) 60 pt Amplatzer study § European Society of Cardiology: weak recommendation for those with high stroke risk and contraindication to long-term • Both non-randomized anticoagulation • Off anticoagulation • Lower than predicted stroke / embolism rates § Not yet part of US guidelines • 4% thrombus formation on § FDA: “suitable for warfarin” + “appropriate reason to seek a non- Watchman (can occur late) drug alternative” § Non-appendage clot sites § Hybrid approach: low-dose NOAC + Watchman? Reddy VY et al, JACC 2013; Wiebe J et al, Catheter Cardiovasc Interv 2014 Perk G et al, Eur Heart J Cardiovasc Imaging 2011 Case #4 Case #4 GG is a 60 yo F with PAF and HTN who has episodes despite GG is a 60 yo F with PAF and HTN who has episodes despite treatment with metoprolol. Why should she consider AF ablation? treatment with metoprolol. Why should she consider AF ablation? A. Decrease AF symptomatic burden A. Decrease AF symptomatic burden B. Minimize stroke risk B. Minimize stroke risk C. Decrease likelihood of developing HF C. Decrease likelihood of developing HF D. Improve her survival D. Improve hers survival
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