FDA approval of the left atrial appendage closure device after a long review process provides a potentially useful alternative to warfarin.
The US Food and Drug Administration (FDA) in March finally approved the Watchman, a controversial device designed as a stroke-preventing alternative to warfarin in patients with atrial fibrillation (AF).
The agency’s decision to give the device a limited indication comes nearly 7 years after Boston Scientific first submitted the Watchman for regulatory review.
The FDA declined to approve the Watchman after the company’s first 2 applications. Then, an advisory panel voted last fall to award the narrowest possible endorsement to the left atrial appendage closure device.
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. On the next vote, however, the vote over whether the benefits of use outweighed the risks, 1 member abstained and the motion carried 6-5.
The FDA was not required to follow the panel’s recommendation, but it decided last week to approve the device as a warfarin substitute but only for patients who “have an appropriate rationale to seek a non-pharmacologic alternative to warfarin.” The announcement did not, however, explain what rationales were “appropriate.”
Use of the device will also be limited, at least at first, to facilities that learned how to install it properly during clinical trials. Other medical centers will begin offering the device when staff members are able to receive training from Boston Scientific.
Last year’s panel vote marked the third time that independent experts have 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 in 2013, when another panel voted 13-1 in favor of the Watchman on all 3 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 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.
Since then, researchers have published more data about the Watchman device, data that came from long-term follow-up of the earlier PROTECT AF trial.
Researchers, who published their findings in in the Journal of the American Medical Association (JAMA), used the Watchman on 463 patients and warfarin on 244 patients and followed them for an average of 3.8 years (standard deviation, 1.8 years).
There were 39 events (defined as stroke, systemic embolism, and cardiovascular or unexplained death) among the 463 patients in the device group (8.4%), which translates into a primary event rate of 2.3 events per 100 patient-years. In the warfarin group, however, there were 34 events among 244 patients (13.9%), which translates into a primary event rate of 3.8 events per 100 patient-years (rate ratio, 0.60; 95% credible interval, 0.41-1.05).
Those results met pre-specified criteria for both non-inferiority (posterior probability, >99.9%) and superiority (posterior probability, 96.0%).
The new results, like those that came before, elicited some controversy. A letter to the editor questioning both the results and the researchers appeared in the latest addition of JAMA, along with a response from 2 study authors.
The letter asked, among other things, whether there had been autopsies for the 53 Watchman-group patients who died during follow-up and whether the researchers had collected information about non-fatal heart failure in both groups.
The letter also asserted that the study results needed to be replicated because 9 of the 12 authors of the study, which was financed by Boston Scientific, disclosed potential conflicts of interests and because the study’s lead author will receive royalties on device sales.
The study authors replied that autopsies had not been conducted and that they had not compared heart failure rates between the study group and the control. They noted, however, that an independent data and safety board had reviewed all the data and that the study complied with all requirements from the FDA.
The Watchman’s approval provides physicians with another option for treating patients with AF, but it is an option that has yet to be tested against other warfarin alternatives such as novel oral anticoagulants that have become popular since Boston Scientific first submitted its device for approval back in 2008.