An hour before the presentation of the PREVAIL study, the ACC announced the cancellation of the release of the study results. Due to an error in the email system, results of the study were reported a few hours before his presentation. The ACC in an unprecedented decision cancelled the presentation of the study as well as press conference.
Antithrombotic therapy with warfarin remains the gold standard for the prevention of thromboembolic events in patients with atrial fibrillation (AF). However, due to the increased risk of bleeding with this therapy, devices to occlude the left atrial appendage at the point of maximum thrombus formation have been developed. They are now available in Europe but were rejected by the U.S. FDA due to security concerns raised by the PROTECT study, which showed a high initial rate of pericardial effusion and stroke related to the procedure. The PREVAIL study was performed in order to provide more information and confirm the safety and effectiveness of the results presented in the PROTECT study.
Methods: We performed a non-inferiority randomized, (2:1), multicenter study which included 475 patients with non-valvular AF with a CHADS ≥ to 2 to device implantation or to conventional anticoagulant therapy with warfarin. The aim of the study was to evaluate the safety and efficacy of the device. The success rate of the device implantation was 95.1%. The primary safety endpoint for the device (the occurrence of death, ischemic stroke, systemic embolism or device-related complications requiring endovascular or cardiovascular intervention) occurred in 2.2%. The secondary composite endpoint security, which included cardiac perforation, pericardial tamponade, ischemic stroke, device embolization or other vascular complications, was 4.4% of patients receiving the Watchman device, (compared with 8.7% in the PROTECT study). The main measure of effectiveness, (comparison between this study and the PROTECT study of stroke, cardiovascular death and unexplained systemic embolism), only showed non-inferiority with a safe superior limit of 95%, slightly higher than allowed to meet with the success criteria, (<1.75%). The secondary endpoint, (comparison of systemic embolism or ischemic stroke, which occurred more than seven days after randomization), met the criteria for non-inferiority, (95% CI upper limit <0.0275%).
Conclusions: The study showed a higher success rate of device implantation and a lower rate of complications than the PROTECT study reaching non-inferiority in efficacy.
Comments: Holmes stressed that these results are very premature, with only a limited number of patients followed for eighteen months, (to date 58 patients and 30 control devices). David Holmes said that despite the high average CHADS ≥ to 2 score of 2.6, the control group showed a lower rate of events, (0.7 per 100 patient-year), compared with other published studies with warfarin. “This low event rate in the control group makes it difficult to demonstrate the effectiveness of the device,” he added. Holmes says that 50% of AF patients do not take anticoagulants and there is a great need for alternatives. “Many people cannot take oral anticoagulants, as they have a high risk of bleeding and others do not like the inconvenience of monitoring. The Watchman device (percutaneously delivered left atrial appendage, LLA) offers the alternative of undergoing a procedure instead of taking anticoagulant therapy for life.”
David Holmes
2013-03-09
Original title: Final Results of Randomized Trial of Left Atrial Appendage Closure Versus Warfarin for Stroke/Thromboembolic Prevention in Patients with Non-Valvular Atrial Fibrillation (PREVAIL)
