Left atrial appendage closure (LAAC) with the Watchman device prevents stroke in patients with nonvalvular atrial fibrillation (AFib) comparable to warfarin, with reduced major bleeding and mortality, according to the five-year results of the PREVAIL and PROTECT-AF trials, presented at TCT 2017 and simultaneously published in the Journal of the American College of Cardiology.

Vivek Y. Reddy, MD, et al., reported the final, five-year results of PREVAIL, both alone and as part of a patient-level meta-analysis with PROTECT-AF five-year data. In the two trials combined, 1,114 patients with nonvalvular AFib were randomized to LAAC with the Watchman device (n = 732) or warfarin (n = 382) for 4,343 patient-years. The first primary efficacy endpoint in PREVAIL was the same as the primary endpoint in PROTECT-AF – the composite of stroke, systemic embolism or cardiovascular/unexplained death. In PREVAIL, the second primary efficacy endpoint was the composite of ischemic stroke or systemic embolism after seven days post randomization. The event rates were calculated as events per 100 patient-years.

In PREVAIL, the first primary endpoint did not achieve non-inferiority of the device to warfarin, with a calculated 18-month rate of 0.066 for LAAC compared with 0.051 for warfarin. The second primary endpoint did achieve non-inferiority, with a calculated 18-month rate of 0.0255 for LAAC vs. 0.0135 for warfarin.

In the meta-analysis, the rates of the composite of stroke, systemic embolism or cardiovascular/unexplained death were similar between groups (p = 0.27). The rates of all stroke or systemic embolism were also similar (p = 0.87). However, there was a large significant reduction in hemorrhagic stroke with LAAC vs. warfarin (hazard ratio, 0.20; p = 0.0022). With LAAC, there were significantly fewer disabling or fatal strokes (p = 0.027) and significantly lower rates of cardiovascular or unexplained death (p = 0.027). LAAC was also superior with respect to all-cause death (p = 0.035) and major bleeding (p = 0.0003).

Limitations of PREVAIL that might explain the failure of the first primary endpoint to achieve noninferiority include the lack of statistical power and the unusually low ischemic stroke rate (0.73 percent) in the warfarin group due to small sample size.

The five-year outcomes of PREVAIL and PROTECT-AF demonstrate that LAAC with the Watchman device provides similar stroke prevention as anticoagulation in patients with nonvalvular AFib. According to the authors, "the primary benefit of LAAC is the ability to avoid oral anticoagulation (OAC) and its associated bleeding risk…By minimizing major bleeding, particularly hemorrhagic stroke, LAAC results in less disability or death than warfarin." "For patients who are poor candidates for long-term oral anticoagulation, LAAC is a reasonable strategy for stroke prophylaxis," they concluded.

In a related editorial, Jacqueline Saw, MD, FACC, commented, "Although the consummate clinical trialist would demand a more robust study methodology, it is reasonable to accept the available data from PREVAIL despite these potential flaws."

According to Dr. Saw, the patient-level meta-analysis of PROTECT-AF and PREVAIL provides additional data that helps address the limitations of PREVAIL. "Reductions of cardiovascular and all-cause mortality is a remarkable feat with this device therapy, and emphasizes one of the key benefits with LAAC, which is reduction of major bleeding and associated complications with lifelong OAC administration," she concluded.

Keywords: Atrial Appendage, Atrial Fibrillation, Warfarin, Anticoagulants, TCT17, Transcatheter Cardiovascular Therapeutics

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