Original Investigation
5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials

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Abstract

Background

The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time.

Objectives

The final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years.

Methods

PREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analyses are by intention-to-treat, and rates are events per 100 patient-years.

Results

For the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p = 0.27), as were all-stroke/SE (HR: 0.961; p = 0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p = 0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAAC (HR: 0.20; p = 0.0022; HR: 0.45; p = 0.03; HR: 0.59; p = 0.027; HR: 0.73; p = 0.035; HR: 0.48; p = 0.0003, respectively).

Conclusions

These 5-year outcomes of the PREVAIL trial, combined with the 5-year outcomes of the PROTECT AF trial, demonstrate that LAAC with Watchman provides stroke prevention in nonvalvular atrial fibrillation comparable to warfarin, with additional reductions in major bleeding, particularly hemorrhagic stroke, and mortality. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy; NCT01182441)

Key Words

atrial fibrillation
left atrial appendage
left atrial appendage closure
oral anticoagulation
stroke prevention
warfarin
Watchman

Abbreviations and Acronyms

AF
atrial fibrillation
CI
confidence interval
FDA
U.S. Food and Drug Administration
HR
hazard ratio
INR
international normalized ratio
LAA
left atrial appendage
LAAC
left atrial appendage closure
NOAC
nonwarfarin oral anticoagulation
OAC
oral anticoagulation
PY
patient-years
RCT
randomized control trial

Cited by (0)

The PREVAIL and PROTECT AF clinical trials were funded by Boston Scientific, the manufacturer of the Watchman LAA closure device used in this trial (which acquired the company that initiated these trials, Atritech). Dr. Reddy has received research grant support from and has been a consultant for Abbott, Biosense Webster, and Boston Scientific. Dr. Doshi has received research grants and consulting fees from Abbott, Biosense Webster, Boston Scientific, and SentreHeart; and is the national principal investigator of the Continuous Access Registry (CAP2). Dr. Kar has received research grants from and served as a consultant for Abbott Vascular and Boston Scientific; has served as a member of the advisory board for left atrial appendage closure; is the national principal investigator of the Continuous Access Registries (CAP and CAP2); and has served as a proctor for Boston Scientific. Dr. Gibson has received speaker and proctoring fees from SentreHeart and Boston Scientific. Dr. Price has received consulting honoraria from Abbott Vascular, Boston Scientific, W.L. Gore, Medtronic, and AstraZeneca; has received speaker honoraria from Abbott Vascular, Medtronic, Terumo, and AstraZeneca; has served as a site investigator for trials involving the Watchman device; has received honoraria as a proctor for Abbott Vascular and Boston Scientific; and is a member of the Steering Committee for the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry. Dr. Huber has served on the Watchman Advisory Board for Boston Scientific. Dr. Horton has received consulting fees from Boston Scientific. Dr. Buchbinder has received research grant support from and has been a consultant for Boston Scientific. Dr. Neuzil has received grant support and consulting fees from Abbott, Biosense Webster, and Boston Scientific. Nicole T. Gordon is a salaried employee of and owns stocks in Boston Scientific. Dr. Holmes and Mayo Clinic have a financial interest in technology related to this research; that technology has been licensed to Boston Scientific. Deepak L. Bhatt, MD, MPH, served as Guest Editor-in-Chief for this paper. Jacqueline Saw, MD, served as Guest Editor for this paper.

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