FDA Panel Narrowly Approves Atrial Fibrillation Device

A experimental device designed to replace medications such a warfarin in the treatment of nonvalvular atrial fibrillation (AF) may have taken another step closer to market earlier this month.

The Circulatory System Devices Panel of the US Food and Drug Administration (FDA) gave the narrowest possible endorsement to a left atrial appendage closure device known as the Watchman.

Panel members, who unanimously agreed that research had proven the device safe, split 6-6 on whether research had proven it effective for the prevention of ischemic stroke and systemic embolism, and the reduction of bleeding risk. Panel chair Richard Page, MD, broke the tie with a “no” vote. However, on the vote over whether the benefits of use outweighed the risks, one member abstained and the motion carried 6-5.

Page said after the meeting that, despite the apparently sharp divide, panel members actually agreed on the basics: the device is an important piece of new technology, one that certainly belongs on the market, but study results probably do not justify the request by manufacturers to approve it as a first-line treatment for AF.

This vote marked the third time that a panel of experts has recommended that the FDA formally approve the device. The first recommendation came from a narrowly divided panel in 2009, but FDA officials refused approval. The second came late last year, when another panel voted 13-1 in favor of the Watchman on all three of the questions, but FDA officials requested more follow-up data.

The second and third panels have both evaluated the device with information from the PREVAIL trial, which randomized patients with nonvalvular AF on a 2-to-1 basis between the Watchman and warfarin.

The second panel saw data that dated from January 2013 and indicated that there had been 5 ischemic strokes in the Watchman group compared to 1 in the warfarin group.

The third panel saw data that dated from June 28. That data, which provided a median follow-up time of 25.9 months, reported 13 ischemic strokes in the Watchman group compared to just 1 in the warfarin group. The more recent results also reported 2 hemorrhagic strokes, 1 systolic embolism and 8 relevant deaths in the Watchman group compared to 2 hemorrhagic strokes and 6 relevant deaths in the warfarin group.

“The number of new ischemic strokes and the increased ischemic stroke rate in the Watchman group of PREVAIL raise questions about the long-term effectiveness of the Watchman device to protect patients from ischemic stroke,” FDA staff members wrote in a briefing for the panel. “A review of the ischemic stroke event narratives found no mitigating circumstances that could otherwise address the device effectiveness concerns.”

The FDA generally follows advice from its expert panels, but, as its prior decisions concerning the Watchman indicate, it is not obligated to do so.

In this case, the agency could approve the device, reject it, or request still more data and start the process all over again.

Page, the panel chair, said after the meeting that he thought the Watchman could find a place on the market, if its sponsors and the FDA worked together to determine an appropriate indication for use.