This article is more than 5 years old. Information may no longer be current.
FDA panel voted in favor of Watchman device for stroke prevention
Click Here to Manage Email Alerts
The FDA’s Circulatory System Devices Panel voted 13-1 that the benefits of a left atrial appendage closure technology for the prevention of ischemic stroke and systemic embolism and the reduction of bleeding risk in patients with nonvalvular atrial fibrillation outweigh its potential risks.
The panel also voted 13-1 that the device is safe and 13-1 that it is effective. Panel member Richard A. Lange, MD, of the University of Texas, San Antonio, cast the sole dissenting vote in all three cases.
If approved, the device (Watchman, Atritech/Boston Scientific) could be used as an alternative to warfarin.
“This is a transformative technology,” panelist David J. Slotwiner, MD, of Long Island Jewish Medical Center, Hyde Park, N.Y., said. “This represents a new course of management for patients with AF, and it’s very exciting.”
Second review
This is the second time the device has been considered by the agency. The FDA issued a Not Approvable letter for the device in 2010, contrary to the recommendations of the advisory panel, because of concerns over the conduct and execution of the PROTECT AF trial, and requested a new prospective trial.
Boston Scientific primarily made its case for approval based on the results of that new trial, PREVAIL, in which patients assigned to receive the Watchman experienced similar outcomes compared with patients assigned warfarin. The company also presented long-term data from PROTECT AF.
In PREVAIL, the second primary endpoint of acute occurrence of death, ischemic stroke, systemic embolism and procedure- or device-related complications requiring major CV or endovascular intervention was met (95% upper CI limit <2.67%). The rate of ischemic stroke or systemic embolism occurring more than 7 days post-randomization, the study’s third primary endpoint, was also met (95% CI upper limit <0.0275%).
However, the Watchman did not meet non-inferiority criterion for the first primary endpoint of 18-month rates of stroke, systemic embolism and CV or unexplained death. The 95% upper credibility interval limit was 1.89, above the goal of <1.75.
Panelists debated the significance of this missed goal. Some said missing a primary endpoint is an important drawback. However, others argued that the goal — a product of negotiation between the sponsor and the FDA — had no clinical significance, that the raw 18-month endpoint rates of 0.064 for the device group and 0.063 for the control group were virtually identical, and that the rest of the data from PREVAIL, PROTECT AF and the CAP registry overshadowed it.
Lange praised the technology despite his negative vote, which he said he cast because he did not think there were enough data from PREVAIL to indicate that the device was as safe and effective in those patients as it was in the PROTECT AF patients followed long-term. “I think it’s a good technology, I just wish we had all the data,” he said.
Complications reduced
PREVAIL was launched after training programs were conducted with the goal of reducing complication and procedure-related stroke rates. Panelists recommended that such training programs be mandatory if the device makes it to market. The rate of serious vascular complications among Watchman recipients was reduced in PREVAIL participants compared with PROTECT AF participants (8.7% vs. 4.6%; P=.004), as were rates of procedure-related stroke (P=.019) and surgical repairs (P=.027).
The FDA is not required to follow the recommendations of its advisory panels, but usually does. Boston Scientific stated in a press release that it expects an approval decision from the FDA in the first half of 2014.
For more information:
Circulatory System Devices Advisory Panel Clinical Briefing Document. PMA P130013.
Disclosure: The panel members report no relevant financial disclosures.
Perspective
Back to Top
Walid Saliba, MD
We know that patients who have nonvalvular AF have an increased risk of having a stroke, and traditionally, over the past 2-3 decades, the recommendation has been to decrease the risk of stroke with anticoagulation. With the newer anticoagulants that came out over the past 2-3 years, you can take them and don't need to have your blood checked on a regular basis. The problems with the new anticoagulants are that they're expensive, and there's no antidote, so if you're actively bleeding, you can't reverse it right away.
Left atrial appendage occlusive devices theoretically minimize the problems of bleeding seen with anticoagulants and reduce the risk of stroke at least to the same extent. We know from the surgical literature that 90% of strokes that happen in the setting of AF occur because of clot formation in the left atrial appendage. Therefore, taking the left atrial appendage out of the equation is associated with a reduction in the risk of stroke in these patients.
With the device strategy, you may have, at least at the beginning, a little bit of an increased risk in terms of the implant procedure, but follow-up studies showed that that risk is minimal. Once you have the device in, not only is your stroke risk reduced, but you're not exposed to the risk of bleeding that is associated with anticoagulation. At 5 years of follow-up, studies have shown no complications from the device, continuous decrease in the risk of stroke and a decreased mortality risk that is predominantly related to a decrease in bleeding.
There is a minority of patients who cannot be on anticoagulation who may ask for this device, but that's not the bulk of the population with AF. If you have AF and are at risk for stroke, and you have the luxury of choosing warfarin, one of the newer anticoagulants or the device, would you choose the device, or would you take a pill? We have patients at the Clinic who will say, "I'm on medication and I'm doing well, so why would I want to go for a procedure and take more risks?" On the other hand, we will have people who say, "If it's proven that there's a decrease in mortality compared to what I'm taking now, then I'd definitely want to go for the device." It will take more education, more data, and more time to see how it's going to pan out.
Click Here to Manage Email Alerts