March 19, 2010 (Plymouth, Minnesota) — A novel device used to close the left atrial appendage (LAA) and reduce the risk of stroke in warfarin-eligible patients with nonvalvular atrial fibrillation (AF) requires further study, according to the Food and Drug Administration (FDA).
Atritech (Plymouth, MN), the maker of the Watchman device, announced that the company "obtained clarity" from the FDA, essentially meaning that another study is needed before the Watchman can be approved. The study is meant to provide more safety and effectiveness data, and although the details of the study have not yet been finalized, Atritech said that it will be working closely with the FDA in designing the trial.
In April 2009, an advisory panel voted 7 to 5 in favor of approving the device for closure of the LAA, but the cautious approval came with conditions, including that implantation be performed in centers with surgical backup and the creation of a physician-certification program. The panel also recommended the creation of a registry and extended follow-up of current clinical trials.
More Needed Than PROTECT-AF
The advisory panel recommendations, as previously reported by heartwire, were based on the results of the Embolic Protection in Patients with Atrial Fibrillation (PROTECT-AF) trial, the pivotal premarket approval study. The results of PROTECT-AF were presented at the i2 Summit of the American College of Cardiology (ACC) 2009 Scientific Sessions and showed that that theWatchman device was associated with a reduction in hemorrhagic stroke risk vs warfarin, and all-cause stroke and all-cause mortality outcomes were noninferior to warfarin.
During the April 2009 meeting, FDA analysts and panel members expressed concern about the "complex" and "unusual" trial design, particularly about using a noninferiority hypothesis when comparing a drug with a device. Also problematic were a number of confounding variables, including the use of antiplatelet therapies and whether or not the device could be used in the general population. The PROTECT-AF study included patients at a lower risk of stroke, those with a CHADS2 score of 1 or 2.
Speaking with heartwire, panel member Dr John Somberg (Rush University Medical Center, Chicago, IL), who voted in favor of approving the device, said the additional study is likely being requested to clear up some of these lingering questions.
"It was a more difficult study to do--a drug vs a device--and it certainly had a lot of operator specificity, and there is a learning curve with the device," he said. "But this has been done before, and I think the company did a credible job with the trial. I assume the FDA is looking for additional data to clarify the safety profile. My take is that in the right hands, this is a viable product, and I'm usually a difficult person to convince."
Asked if he thought the delay signaled a shift toward tougher standards in getting devices approved, Somberg said he does not believe this to be the case and that the request is more likely the result of the mixed 7 to 5 vote in favor of approval.
"Devices are different from drugs," Somberg told heartwire . "There is not a requirement for two randomized, blinded, usually placebo-controlled studies. With devices, usually one adequately controlled study is sufficient. I would say that devices are, have been, and probably will continue to be more easily approved, because by their very nature they go through various iterations and changes along the way. It's not a drug, where if you change one hydroxyl or carbon atom you're changing the molecule irrevocably. So I would say that it's not that they're raising the standards for devices, it's just that they're faced with a mixed panel decision for an implantable, invasive device."
This week in the New England Journal of Medicine, Dr Alan Garber (Stanford University, CA) addresses the FDA's regulation of devices and how the approval process differs from the rigors of getting a new drug to market . He writes that in addition to premarket evaluations, postapproval studies, with longer follow-up, would allow researchers to track delayed risks and benefits of the new devices. "This is the right time to institute a more comprehensive approach to the postapproval monitoring and analysis of the safety and effectiveness of medical devices," writes Garber.
Follow-up Data Available to 23 Months
Just a few days ago, at this year's i2 Summit/ACC meeting, Dr David Holmes (Mayo Clinic, Rochester Clinic) presented follow-up data out to 23 months on the safety and effectiveness of the Watchman device in the PROTECT-AF study.
The relative risk for the primary safety end point, a composite that included device embolization requiring retrieval, pericardial effusion requiring intervention, and cranial, gastrointestinal, or any other significant bleed, decreased from 2.08 in the early experience to 1.60 after 23 months, reported Holmes.
The primary efficacy end point, which included all strokes, including ischemic and hemorrhagic; cardiovascular or unexplained death; and systemic embolization, met the criteria for noninferiority in the main trial and also performed well at 23 months. The relative reduction in risk with the Watchman device compared with warfarin therapy was 31%.
The next FDA-required study will likely be smaller and shorter than the PROTECT-AF study, but it is unknown when the trial will be started or completed. In August 2008, Atritech initiated the Continued Access PROTECT-AF (CAP) registry, and 420 patients have been implanted with the LAA-closure device to date.
Heartwire from Medscape © 2010
Cite this: Watchman Delayed: FDA Wants More Data on the LAA-Closure Device Before Approving - Medscape - Mar 19, 2010.