Author + information
- Received December 20, 2013
- Revision received February 25, 2014
- Accepted April 3, 2014
- Published online July 8, 2014.
- David R. Holmes Jr., MD∗∗ (, )
- Saibal Kar, MD†,
- Matthew J. Price, MD‡,
- Brian Whisenant, MD§,
- Horst Sievert, MD‖,
- Shephal K. Doshi, MD¶,
- Kenneth Huber, MD# and
- Vivek Y. Reddy, MD∗∗
- ∗Mayo Clinic, Rochester, Minnesota
- †Cedars Sinai Medical Center, Los Angeles, California
- ‡Scripps Clinic, La Jolla, California
- §Intermountain Medical Center, Salt Lake City, Utah
- ‖Cardiovasculares Centrum, Frankfurt, Germany
- ¶Pacific Heart Institute, Santa Monica, California
- #Saint Luke’s Mid America Heart Institute, Kansas City, Missouri
- ∗∗Mount Sinai School of Medicine, New York, New York
- ↵∗Reprint requests and correspondence:
Dr. David R. Holmes, Jr., Mayo Clinic, 200 First Street SW, Rochester, Minnesota 55905.
Background In the PROTECT AF (Watchman Left Atrial Appendage Closure Technology for Embolic Protection in Patients With Atrial Fibrillation) trial that evaluated patients with nonvalvular atrial fibrillation (NVAF), left atrial appendage (LAA) occlusion was noninferior to warfarin for stroke prevention, but a periprocedural safety hazard was identified.
Objectives The goal of this study was to assess the safety and efficacy of LAA occlusion for stroke prevention in patients with NVAF compared with long-term warfarin therapy.
Methods This randomized trial further assessed the efficacy and safety of the Watchman device. Patients with NVAF who had a CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and previous stroke/transient ischemic attack) score ≥2 or 1 and another risk factor were eligible. Patients were randomly assigned (in a 2:1 ratio) to undergo LAA occlusion and subsequent discontinuation of warfarin (intervention group, n = 269) or receive chronic warfarin therapy (control group, n = 138). Two efficacy and 1 safety coprimary endpoints were assessed.
Results At 18 months, the rate of the first coprimary efficacy endpoint (composite of stroke, systemic embolism [SE], and cardiovascular/unexplained death) was 0.064 in the device group versus 0.063 in the control group (rate ratio 1.07 [95% credible interval (CrI): 0.57 to 1.89]) and did not achieve the prespecified criteria noninferiority (upper boundary of 95% CrI ≥1.75). The rate for the second coprimary efficacy endpoint (stroke or SE >7 days’ postrandomization) was 0.0253 versus 0.0200 (risk difference 0.0053 [95% CrI: –0.0190 to 0.0273]), achieving noninferiority. Early safety events occurred in 2.2% of the Watchman arm, significantly lower than in PROTECT AF, satisfying the pre-specified safety performance goal. Using a broader, more inclusive definition of adverse effects, these still were lower in PREVAIL (Watchman LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial than in PROTECT AF (4.2% vs. 8.7%; p = 0.004). Pericardial effusions requiring surgical repair decreased from 1.6% to 0.4% (p = 0.027), and those requiring pericardiocentesis decreased from 2.9% to 1.5% (p = 0.36), although the number of events was small.
Conclusions In this trial, LAA occlusion was noninferior to warfarin for ischemic stroke prevention or SE >7 days’ post-procedure. Although noninferiority was not achieved for overall efficacy, event rates were low and numerically comparable in both arms. Procedural safety has significantly improved. This trial provides additional data that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF who do not have an absolute contraindication to short-term warfarin therapy.
This study was sponsored by Atritech/Boston Scientific. Dr. Holmes (along with the Mayo Clinic) have a financial interest in technology related to this research; that technology has been licensed to Atritech. Dr. Kar receives research grants from Boston Scientific; is a member of the advisory board for left atrial appendage closure; is the national principal investigator of the Continuous Access Registry (CAP2); receives research grants from St. Jude Medicalhttp://dx.doi.org/10.13039/100006279 and Abbott Vascular; and is a consultant for Abbott Vascular. Dr. Price has received consulting honoraria from Boston Scientific, St. Jude, Janssen Pharmaceuticals, Daiichi-Sankyo, and Terumo; and his institution receives research support from Boston Scientific, St. Jude, and SentreHEART. Dr. Whisenant is a stockholder in Coherex Medical. Dr. Sievert receives study honoraria, travel expenses, consulting fees <$25,000 from Abbott, Access Closure, AGA, Angiomed, Aptus, Atrium, Avinger, Bard, Boston Scientific, Bridgepoint, Cardiac Dimensions, CardioKinetix, CardioMEMS, Coherex, Contego, Covidien, CSI, CVRx, EndoCross, ev3, FlowCardia, Gardia, Gore, Guided Delivery Systems, InSeal Medical, Lumen Biomedical, HLT, Lifetech, Lutonix, Maya Medical, Medtronic, NDC, Occlutech, Osprey, Ostial, PendraCare, pfm Medical, Recor, ResMed, Rox Medical, SentreHEART, Spectranetics, SquareOne, Svelte Medical Systems, Trireme, Trivascular, Venus Medical, Veryan, and Vessix; he has received grant research support <$25,000 from Cook and St. Jude Medical; and he has stock options <$25,000 from Cardiokinetix, Access Closure, Velocimed, Lumen Biomedical, Coherex, and SMT. Dr. Doshi is a consultant for Atritech/Boston Scientific. Dr. Huber is on the Watchman Advisory Board for Boston Scientific. Dr. Reddy has received research grant support and consultant fees from Boston Scientific, Coherex, and St. Jude Medical.
- Received December 20, 2013.
- Revision received February 25, 2014.
- Accepted April 3, 2014.
- American College of Cardiology Foundation