SAN FRANCISCO—After one week of flip-flopping on whether or not to release the complete results of the PREVAIL trial—that evaluates the Watchman device compared with warfarin for stroke prevention— the trial’s sponsor Boston Scientific “broke its own embargo,” according to American College of Cardiology’s (ACC) Director of Media Relations’ Beth Casteel, and the ACC decided to pull the trial as a late-breaker approximately one hour before it was set to be presented.
The ACC, however, had previously released the trial’s results in an embargoed fashion. The study met two of its three primary endpoints, but the overall results showed that left atrial appendage closure with the Watchman device has gotten safer for stroke prevention in atrial fibrillation.
In this prospective, multicenter study, the researchers randomized 407 patients with non-valvular atrial fibrillation at risk of stroke in a 2:1 fashion to receive either the Watchman device or conventional therapy with warfarin. They used the CHADS2 score to assess patients’ risk of stroke, which includes such factors as congestive heart failure, high blood pressure, age, diabetes, prior stroke or transient ischemic attack.
The Watchman is a fabric-covered, self-expanding device that fits over the appendage opening and is permanently implanted or placed to prevent blood flow from exiting the left atrial appendage and causing a stroke. “The device works by separating this thumb-sized appendage and blocking it off as if you were to put a cover on a pipe so nothing can go in or come out,” said PREVAIL’s co-principal investigator David R. Holmes, Jr., MD, professor of medicine at Mayo Clinic College of Medicine, Rochester, Minn., past president of ACC, in a pre-organized ACC press release.
Overall, the trial’s patient population was older, had higher CHADS2 scores, more diabetes and a higher history of prior stroke or transient ischemic attack than the earlier, pivotal trial, PROTECT AF trial.
Despite the reduction in hemorrhagic stroke compared with warfarin, PROTECT AF study showed an increase in perioperative events, mainly pericardial effusion in patients implanted with the device. As a result, one of PREVAIL’s three co-primary endpoints was the composite of acute death or serious vascular complications (e.g., cardiac perforation, pericardial effusion, ischemic stroke, device embolism) that could relate to the procedure or device for seven days after implantation.
Compared with PROTECT AF, serious vascular complications were markedly reduced (8.7 vs. 4.4 percent) in the seven days post-randomization and cardiac perforation requiring surgical repair (1.6 vs. 0.4 percent).
Success rates for implanting the device also were higher in PREVAIL. Although PREVAIL was similarly designed to PROTECT AF, it was expanded to include new centers and implanting physicians to help demonstrate the effectiveness of training programs. Data showed very little difference in outcomes between implanting physicians who had experience with the procedure and newly trained operators. There were no procedure-related deaths reported in either trial.
The overall study implant success was 95.1 percent. The 26 experienced operators had a success rate of 96.3 percent, while the 24 new operators had a success rate of 93.2 percent.
On the second co-primary endpoint, researchers found no differences in the rates of stroke, systemic embolism and cardiovascular or unexplained death between both groups at 18 months of follow up using Bayesian piecewise exponential techniques; although there were a limited number of patients with 18 month follow- up data. This secondary non-inferiority endpoint was not met, exceeding the upper 95 percent confidence interval bound. The researchers attempted to explain this through an “over-performing control group.”
In contrast, the third co-primary of ischemic stroke or systemic embolism occurring greater than seven days post-implant met the primary pre-specified non-inferiority criterion. The Watchman 18-month rate was 0.0253 compared 0.0201 in the control (warfarin) group.
Holmes et al concluded that the Watchman device is an alternative to oral anticoagulation therapy for thromboembolic prevention in patients with non valvular atrial fibrillation.
Both the Mayo Clinic and Holmes have a financial interest in technology related to this research. The technology was initially licensed to Atritech, which was acquired by the Natick, Mass.-based Boston Scientific in January 2011 for $375 million.