New catheter based strategies like mechanical occlusion of the Left Atrial Appendage (LAA) with a Watchman device or ligation of the LAA (LARIAT procedure) have been developed in the recent past for prevention of stroke in patients with atrial fibrillation (AF). In the PROTECT-AF study, LAA occlusion was shown to be non-inferior to warfarin for the prevention of the primary composite endpoint of stroke, death and systemic embolism. Another study , the PREVAIL trial(1), was recently conducted to address the concerns regarding the trial design, definition of endpoints and the higher incidence of peri-procedural adverse events in the PROTECT-AF study. The PREVAIL study, when compared with the PROTECT-AF study, included a higher risk group i.e., the patients were older (74.0 ± 7.4 years vs. 71.7 ± 8.8 years) and had higher CHADS2 scores (2.6 ± 1.0 vs. 2.2 ± 1.2).

The study enrolled 407 patients; 269 were randomized to the device group in whom watchman device was implanted and 138 to the control group who received warfarin during the study with a mean follow up of 11.8± 5.8 months. First primary efficacy end-point was a composite of stroke & systemic embolism and cardiovascular/unexplained death. The mean 18-month event rate ratio of the primary efficacy endpoint was 1.07 (95% credible interval (CI): 0.57 to 1.89, 0.064 device vs 0.063 control). As the upper boundary of 1.89 was not lower than the pre-specified non-inferiority margin of 1.75, statistical non-inferiority was not achieved. This was attributed to substantially lower-than-expected number of events, particularly in the control group. Second primary efficacy endpoint, which is the rate of stroke or SE > 7days after randomization was 0.0253 for the device group and 0.0200 for the control group (18-month risk difference 0.0053 [ 95% CrI: -0.0190 to 0.0273]). Because the 95% upper CrI of risk difference was <0.0275 (which was the rate difference non-inferiority criterion), the Watchman device was considered non-inferior to warfarin for prevention of second primary efficacy endpoint.

Procedural success, defined as device deployment and release increased from 90.9% in PROTECT AF to 95.1% in PREVAIL. Procedural complications within 7 days of the procedure decreased from 8.7% in PROTECT AF to 4.2% in the PREVAIL.

Conclusion: This multicenter randomized study showed: 1) Combined efficacy endpoint of early and late events was similar with Watchman device but did not meet the criteria of non-inferiority. 2) LAA occlusion with Watchman device was non-inferior to chronic warfarin for the prevention of stroke and SE beginning 1 week after randomization. 3) Procedural complications occurring after LAA occlusion were infrequent and decreased significantly when compared to PROTECT AF trial.

Reference:

1. Holmes DR, Jr., Kar S, Price MJ et al. Prospective randomized evaluation of the Watchman Left Atrial Appendage Closure device in patients with atrial fibrillation versus long-term warfarin therapy: the PREVAIL trial. Journal of the American College of Cardiology 2014;64:1-12.