The FDA’s Circulatory System Devices Panel split its vote today after reconsidering whether a left atrial appendage closure device should be approved for prevention of stroke and systemic embolism and reduction of bleeding risk in patients with nonvalvular atrial fibrillation.
The panel voted 12-0 that the LAA closure device (Watchman, Atritech/Boston Scientific) is safe; 6-7 (with a tie-breaking vote by panel chair Richard L. Page, MD) that it is not effective; and 6-5, with one abstention, that its benefits outweigh its risks.
Despite the split vote, the panel had a consensus that the device’s indications for use were too broad as currently written, and that it should be considered only as a second-line therapy for appropriate patients.
Page, of the University of Wisconsin School of Medicine and Public Health, said that he voted no on the effectiveness of the device only because he did not think the current indications were supported by the data, but that he would have voted yes on its safety and on its benefits outweighing risks if needed.
“I think this device is important technology,” he said. “We’ve got to have it available. But it’s got to be available for the right people. The indication as written [is] unfortunate … but I heard consensus from everyone in the room, including the sponsor, that this is not first-line. I think this device has a home, and we just need the FDA and the sponsor to work together to develop a description for indication that’s appropriate and gives this important technology a place in our armamentarium to care for our patients with [AF] at risk of [cerebrovascular accident] from embolic stroke.”
Panel member David J. Slotwiner, MD, of Long Island Jewish Medical Center, New Hyde Park, N.Y., said that he voted no on effectiveness and on the benefit outweighing the risk because “I don’t feel comfortable with the broad indication as labeled. But … I would feel comfortable with … rewording, and clearly stating in the indications that this is not equivalent to warfarin, [and is] a second-line therapy.”
In December, the panel voted 13-1 that the benefits of the left atrial appendage closure technology (Watchman, Atritech/Boston Scientific) for the prevention of ischemic stroke and systemic embolism and the reduction of bleeding risk in patients with nonvalvular atrial fibrillation outweighed its potential risks. It also voted 13-1 that the device was safe and 13-1 that it was effective.
At that meeting, available data from the PREVAIL trial, in which patients with nonvalvular AF were randomized on a 2:1 basis to receive the Watchman device or warfarin, indicated that there had been five ischemic strokes in the Watchman group compared with one in the warfarin group.
The dataset reviewed at the December 2013 panel meeting was locked during January 2013, according to a briefing document prepared for the panel by FDA staff. “The sponsor responded on September 5, 2013 that they would conduct an updated analysis, which would be provided prior to the December 2013 panel meeting. However, this update was inadvertently not provided,” the FDA staff wrote.
Since then, the sponsor has provided two updated analyses, the most recent representing a dataset locked on June 28. At the time of this second update, after a mean follow-up of 25.9 months, there were 24 primary endpoint events in the Watchman group (13 ischemic strokes, two hemorrhagic strokes, one systolic embolism and eight CV-related or unexplained deaths) compared with nine in the warfarin group (one ischemic stroke, two hemorrhagic strokes and six CV-related or unexplained deaths), according to the document.
“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,” the FDA staff wrote in the briefing document. “A review of the ischemic stroke event narratives found no mitigating circumstances that could otherwise address the device effectiveness concerns.”
The FDA is not required to follow the recommendations of its advisory panels, but usually does.
For more information:
Circulatory System Devices Advisory Panel Clinical Briefing Document. PMA P130013.