Stroke Prevention in Atrial Fibrillation Old Standards, New Developments, and the Future Michael Rinaldi, MD The Sanger Heart and Vascular Institute Carolinas HealthCare System Charlotte NC USA michael.rinaldi@carolinashealthcare.org Disclosures Consultant: Abbott Vascular Boston Scientific St Jude Medical The AF Epidemic Projected Number of Adults With Atrial Fibrillation in the United States Between 1995 and 2050 Projected Number of Adults with Atrial Fibrillation in the United States Extrapolation of Kaiser Permanente data Go, A S et al JAMA 2001;285:2370-2375 Copyright restrictions may apply AF is a Major Cause of Stroke LAA source of embolic stroke in 90% Assessment of Thromboembolic Risk CHA2DS2-VASc CHF/ LV dysfunction Hypertension Age 75 years Diabetes mellitus Stroke/TIA/TE Vascular disease (CAD, AoD, PAD) Age 65–74 years Sex category (female) 1 2 1 Score 0–9 Lip GY, et al Chest 2010;137(2):263–272 Olesen JB, et al BMJ 2011;342:d124 Stroke Prevention: Pharmacologic Options Stroke or systemic embolism Relative Hazard Ratio (95% CI) Category Intracranial haemorrhage W vs Dabigatran 110 W vs Placebo W vs Rivaroxaban W vs Wlow dose W vs Dabigatran 150 W vs Aspirin W vs Apixaban W vs Aspirin + Clop 0.3 0.6 0.9 1.2 1.5 1.8 2.0 W vs Ximelagatran Major bleeding W vs Dabigatran 110 W vs Rivaroxaban W vs Dabigatran 110 W vs Dabigatran 150 W vs Rivaroxaban W vs Apixaban W vs Dabigatran 150 0.3 0.6 0.9 1.2 1.5 1.8 2.0 Favours Favours other Rx warfarin W vs Apixaban 0.3 0.6 0.9 1.2 1.5 1.8 2.0 Favours Favours other Rx warfarin Modified from Camm A.J EHJ 2009;30:2554-5 Bleeding Risk Prediction with Oral AC HAS-BLED Score Score Bleeds per 100 pt-yrs 1.13 1.02 1.88 3.74 8.70 New Oral AC Drugs vs Warfarin Study RE-LY1 Treatment Major Bleeding Hemorrhagic Stroke Dabigatran (110 mg) 2.71% 0.12% Dabigatran (150 mg) 3.11% 0.10% Warfarin 3.36% 0.38% Rivaroxaban 3.6% 0.5% Warfarin 3.4% 0.7% Apixaban 2.13% 0.24% Warfarin 3.09% 0.47% ROCKET-AF2 ARISTOTLE3 Non Pharmacologic Options for Stroke Prevention A more superior lobe is selected and guice is positioned Compare new position (left) with first position (right) Watchman is deployed and Tug Test performed to assure stability First deployment canted and less stable Second deployment more coaxial and stable The Watchman Device PROTECT-AF:Overview Randomized FDA-IDE Trial Can the WATCHMAN device replace Warfarin? Non-Valvular AF CHADs ≥ Efficacy Endpoint: Stroke CV death (& Unknown) Systemic embolism Randomization (1:2) Safety Endpoint Non-inferiority & Superiority Bayesian Sequential Design Analysis at 600 pt-yrs & every 150 pt-yrs thereafter  1500 pt-yr Follow-up till years Warfarin Watchman Follow-Up Patient Study Timeline PostImplant Day Day 45 Day 180 Ongoing WATCHMAN Day 2-14 Pre-implant interval Patient gets WATCHMAN Patient takes Warfarin Patient discontinues Warfarin / takes Clopidogrel Patient discontinues Clopidogrel Control Randomize Control patient takes Warfarin Day Ongoing Vascular Complications Day Serious Procedure/Device Related  Composite of vascular complications includes cardiac perforation, pericardial effusion with tamponade, ischemic stroke, device embolization, and other vascular complications1 10.0% p = 0.005 8.7% % of Patients 8.0% 6.0% 4.0% 2.0% n=39 4.1% 4.4% n=23 n=12 0.0% PROTECT AF CAP PREVAIL No procedure-related deaths reported in any of the trials PROTECT AF Long Term (4 Year Follow-up) Rate per 100 patient years Events in PROTECT AF trial at 2,621 patient years 10 34% lower 60% lower 40% lower P=0.0379 P=0.0045 PS = 0.96 4.8 3.8 3.2 2.4 2.3 1.0 Primary Efficacy CV or Unexplained Death WATCHMAN Group N=463 All-Cause Death Warfarin Group N=244 Ps = Posterior Probability for Superiority All three endpoints met statistical superiority Protect AF and Prevail Pooled Analysis What About Absolute Oral AC Contraindicated Patients? ASAP Registry 150 AF patients contraindicated for LT warfarin therapy Rate of Success with implantation in warfarin contraindicated patients • Patients had a history of hemorrhagic & bleeding tendencies or a hypersensitivity to warfarin • 150 patients enrolled at European centers • Average CHADS2 = 2.8 94.7% successfully implanted • Post procedure anti-platelet regimen – Clopidogrel through months – Aspirin indefinitely • Patients were followed for up to year – Follow-up @ 3, 6, 12, 18 & 24 months – TEE at and 12 months ASAP Registry Efficacy outcome versus expected 8.0% Ischemic Stroke 7.3% Expected, based on CHADS₂ Score Ischemic Stroke Rate (%/pt-yr) 7.0% 6.0% 5.0% 77% Reduction 5.0% 4.0% 64% Reduction 3.0% 1.7% 2.0% 1.0% 0.0% Expected, if Clopidogrel was used throughout follow-up Observed rate in ASAP Conclusions • Oral Anticoagulation is under utilized for stroke prevention in AF • NOACs are a major advance over warfarin for stroke prevention in AF – No monitoring – Equal or superior stroke protection – 50% reduction in IC bleeding – Expensive – Cannot use in severe renal failure Conclusions • LAA Closure with Watchman is an effective alternative to warfarin for stroke prevention in AF • Superiority over warfarin for mortality, bleeding, IC hemorrhage • Equivalent to warfarin for all strokes with higher risk of embolic stroke balanced by lower risk of hemorrhagic stroke • May be particularly well suited to patients with relative or absolute contraindications to oral AC • Untested vs NOACs [...]... 100 patient years Events in PROTECT AF trial at 2,621 patient years 10 9 8 7 6 5 4 3 2 1 0 34% lower 60% lower 40% lower P=0.0379 P=0.0045 PS = 0.96 4.8 3.8 3.2 2.4 2.3 1.0 Primary Efficacy CV or Unexplained Death WATCHMAN Group N=463 All-Cause Death Warfarin Group N=244 Ps = Posterior Probability for Superiority All three endpoints met statistical superiority Protect AF and Prevail Pooled Analysis