Results of the PREVAIL trial were not reported as late-breaking clinical news in San Francisco at the American College of Cardiology meeting last week, but the media coverage garnered around the offending embargo break that took it off the program has provided the study team with myriad opportunities for comment.
The back story
PREVAIL was designed to confirm the safety and efficacy of the Watchman left atrial appendage closure device and to validate the safety of the implant procedure, called into question by results of the previous PROTECT-AF trial. The device may have the potential to replace lifelong warfarin therapy in appropriate patients.
A recent update of PROTECT-AF demonstrated an adverse event rate of 5.5 cases of major bleeding, pericardial effusion, or device embolization per 100 patient years in the device arm after a mean follow-up of 2.3 years versus a rate of 3.6 per 100 patient years in the warfarin-treated control group—a 53% increase in risk with Watchman therapy.
The primary treatment efficacy endpoint in this PROTECT-AF update, however, consisting of stroke, systemic embolus, and cardiovascular death, reflected a 29% reduction in risk for the Watchman device versus warfarin.
To start, a success rate of 95% was reported in PREVAIL for implantation of the Watchman device— a significant improvement over the 90.9% rate in PROTECT-AF.
PREVAIL also met its primary safety endpoint—7-day composite rate of acute occurrence of death, ischemic stroke, systemic embolism, and procedure- or device-related complications at a rate of 2.2%.
A primary efficacy endpoint—the combined rate of stroke, systemic embolism, and cardiovascular/unexplained death at 18 months, was 6.4% in both study arms but did not meet statistical criterion for noninferiority.
The third primary endpoint was the comparison of ischemic stroke or systemic embolism after 7 days. After 18 months the event rate in the Watchman arm was 2.53% versus 2.01% in the warfarin arm, a result that did meet the noninferiority standard.
A narrow indication for the device is predicted, ie, for patients at high risk, in whom warfarin has proved inadequate, or for patients who cannot be safely anticoagulated.
In short, the Watchman data require further examination and the manufacturer Boston Scientific will continue to await approval from the FDA device panel.
Reddy VY, Doshi SK, Sievert H, et al; PROTECT AF Investigators. Percutaneous left atrial appendage closure for stroke prophylaxis in patients with atrial fibrillation: 2.3-year follow-up of the PROTECT-AF (Watchman Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial. Circulation. 2013;127:720-729. doi:10.1161/CIRCULATIONAHA.112.114389.
Husten L. Following An Embargo Break PREVAIL Trial Won't Be Presented At ACC. Forbes. March 9, 2013.
Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy. The PREVAIL Study. Clinical trial data available at: http://www.bostonscientific.com/watchman-eu/clinical-data/prevail-clinical-study.html