Persist & prevail

Are clinical trial names prophetic? PREVAIL may provide the answer.

Yesterday the FDA’s Circulatory System Devices Panel of the Medical Devices Advisory Committee voted 13-1 in favor of the Watchman Left Atrial Appendage Closure device for patients with atrial fibrillation who are at risk of strokes. The panelists made their nearly unanimous vote after a review of the device’s safety and efficacy in two clinical trials, PROTECT AF and PREVAIL.

It has been a long road for the Watchman, which won a slim majority vote by the panel in its favor in 2009. At the time, panelists voiced reservations, given the lack of long-term follow-up data. The FDA followed up with a nonapproval letter on March 10, 2010.

Concerns about longer-term outcomes may have been put to rest earlier this year, with a presentation at the 2013 Heart Rhythm Society scientific session in Denver. Vivek Y. Reddy, MD, of the Cardiovascular Institute at Mount Sinai School of Medicine in New York City, shared results at a press conference.

“There was an approximately 60 percent decrease in cardiovascular death in the Watchman group compared to the control group, which was statistically significant,” he said. The randomized trial compared Watchman with warfarin in 800 patients who were followed for a mean 45 months. “There was also an 85 percent decrease in hemorrhagic stroke in the Watchman group compared to the control group, which was also statistically significant.”

He added a secondary analysis found an unexpected decreased risk of 34 percent in all-cause mortality.

Watchman, which is made by Boston Scientific, has received CE Mark in Europe but remains an investigational device in the U.S. When asked about the likelihood of FDA approval, Reddy responded that “the FDA is difficult to predict.”

PREVAIL was designed by Boston Scientific and the FDA. The agency said the newer trial would augment existing data and overcome some of the limitations in PROTECT AF. PREVAIL enrolled higher risk participants and excluded patients indicated for clopidogrel (Plavix, Bristol Myers-Squibb/Sanofi Aventis) within seven days of enrollment, among other things.

The FDA noted that the trial failed to reach its noninferiority endpoint, a composite of stroke, systemic embolism and cardiovascular or unexpected death compared with warfarin. But it did prevail on the noninferiority endpoint on ischemic stroke and systemic embolism after seven days of implantation.

Is that enough to sway the FDA this time? That is difficult to predict.

Candace Stuart

Cardiovascular Business, editor