BOSTON, MA — A patient-level meta-analysis of subjects with nonvalvular atrial fibrillation treated with the Watchman (Boston Scientific) left atrial appendage (LAA) closure device confirms the device "provides similar benefit" when compared with long-term warfarin use, say researchers.
Regarding the primary efficacy end point of stroke, systemic embolism, or cardiovascular death, the end point used in the PREVAIL and PROTECT AF studies, investigators observed no difference between warfarin and the LAA-closure device in a combined analysis of these two clinical trials.
The meta-analysis, which includes data from the two randomized, controlled trials, plus an analysis of additional patients in nonrandomized registries, is published June 23, 2015 issue of the Journal of the American College of Cardiology by lead researcher Dr David Holmes (Mayo Clinic, Rochester, MN) and colleagues.
Difference in the Type of Strokes
In March, the US Food and Drug Administration (FDA) approved the Watchman for reducing the risk of thromboembolism in high-risk patients with nonvalvular atrial fibrillation. The device, which trudged a difficult path before approval, including three trips before the FDA advisory committee, is meant to be an option for high-risk patients seeking an alternative to warfarin or for those unable to take warfarin. The LAA-closure device has been available for use in Europe for the past 10 years.
In this combined analysis of PREVAIL and PROTECT AF, the rates of stroke or systemic embolism were similar between the two treatment arms—1.75 per 100 patient-years with the Watchman and 1.87 per 100 patient-years with warfarin (P=0.94)—while cardiovascular mortality was reduced 52% with the Watchman device vs warfarin (hazard ratio [HR] 0.48; 95% CI 0.28–0.81). Rates of major bleeding not related to the procedure, defined as bleeding events occurring 7 days postimplantation, were significantly reduced with the Watchman device (HR 0.51; 95% 0.33–0.77).
The researchers did observe significant differences in the types of stroke occurring among patients treated with the two therapies. Rates of ischemic stroke were significantly increased with the Watchman device, with 1.6 ischemic strokes/systemic embolisms occurring per 100 patient-years with the Watchman vs 0.9 ischemic strokes/systemic embolisms per 100 patient-years with warfarin (P=0.05). However, after ischemic events related to the procedure—defined as those within the first 7 days—were excluded, the difference in ischemic stroke was no longer statistically significant.
Hemorrhagic stroke was significantly reduced among patients treated with the Watchman device.
When the meta-analysis was enlarged to include 1145 patients undergoing device implantation in the Continued Access Registry (CAP) and CAP2, the overall results observed in the randomized, controlled trials were similar. Efficacy was similar between the two treatments, and there were significantly fewer cardiovascular deaths and a significant reduction in bleeding. The increase in ischemic stroke observed in the Watchman arm was offset by a significant reduction in hemorrhagic stroke, report the investigators.
Editorialists Not Impressed, Say Concerns Remain
Despite the data, an editorial by Dr Jonathan Waks and Dr Warren Manning (Beth Israel Deaconess Medical Center, Boston, MA) does little to convey confidence in the use of the technology for patients with atrial fibrillation. The long-term safety data for the Watchman device are "incomplete and particularly concerning," they state.
In PREVAIL, for example, the 18-month rate of freedom from stroke and systemic embolism was similar, but 10 of the 13 ischemic strokes occurred beyond 1 year in the Watchman arm. In contrast, there were no new strokes in the warfarin-treated patients. Waks and Manning state that with this differential in late events, the Watchman was no longer statistically "noninferior" to warfarin for non–procedure-related ischemic events.
"Of particular concern, these late ischemic strokes may be related to late thrombus formation on the Watchman device in the absence of anticoagulation," they write. "In a select group of patients, it may be safe, effective, and preferable to chronic warfarin therapy for thromboembolic prophylaxis in atrial fibrillation, but at this point many questions surrounding its safety and long-term efficacy remain unanswered."
The editorialists also note that while treatment with the Watchman significantly reduced the rate of hemorrhagic stroke, the event rate in the warfarin arm was "nearly double the rate reported in other contemporary AF warfarin studies."
As with any new technology, say the editorialists, future iterations of the Watchman will be better and might allow operators to implant the device without the use of anticoagulant or antiplatelet therapy, which would be beneficial, as the population who stands the most to gain with LAA closure are those unable or unwilling to take such treatments.
They point out, though, the number of drugs available to physicians to treat patients with atrial fibrillation has expanded to include the novel oral anticoagulants, and these agents have shown equivalent or improved efficacy over warfarin and lower bleeding rates. This might further reduce the relative benefit of LAA-closure devices compared with pharmacologic stroke prevention.
"At this point in time, it appears that patients treated with Watchman may pay early (procedural complications) and may also possibly pay later (late thromboembolism)," conclude Waks and Manning. "The jury is still out as we await clarity from long-term efficacy data."
Boston Scientific sponsored the PROTECT AF and PREVAIL studies. Holmes and the Mayo Clinic have a financial interest in technology related to this research; the technology has been licensed to Boston Scientific. Disclosures for the coauthors are listed in the article. The editorialists report they have no relevant financial relationships.
Heartwire from Medscape © 2015 Medscape, LLC
Cite this: Watchman Analysis Confirms "Similar Benefit" Compared With Warfarin - Medscape - Jun 15, 2015.