PREVAIL published: Watchman device still shows promise in nonvalvular AF

Left atrial appendage occlusion with the Watchman device may be an acceptable alternative to prolonged warfarin therapy for the prevention of stroke in patients with nonvalvular AF.

The PREVAIL trial, which was initially presented at the American College of Cardiology Scientific Sessions in 2013, was published today in the Journal of the American College of Cardiology and the results confirm those that had been previously presented.

In the study, David R. Holmes, MD, with the Mayo Clinic, Rochester, Minn., and fellow researchers noted that a periprocedural safety hazard was identified with left atrial appendage (LAA) occlusion in the PROTECT AF trial. They undertook the multicenter, randomized, prospective PREVAIL trial to determine whether LAA occlusion with the Watchman device (Boston Scientific) or long-term warfarin therapy was safer and more effective in preventing stroke in a cohort of individuals with nonvalvular AF.

David R. Holmes

Eligibility criteria included a CHADS₂ score of ≥2 or 1 and one other risk factor.

Eligible participants were assigned in a 2:1 ratio to LAA occlusion followed by discontinuation of warfarin therapy or chronic warfarin therapy. There were 269 patients in the occlusion group, which the researchers called the intervention group, and 138 patients in the control group.

A composite of stroke, systemic embolism and CV or unexplained death served as the first co-primary efficacy endpoint, while stroke or systemic embolism >7 days after hospitalization served as the second co-primary endpoint.

Safety confirmed, efficacy less clear

Eighteen-month results indicated that the rate of the first co-primary endpoint was 0.064 in the device intervention group and 0.063 in the control group (rate ratio, 1.07; 95% credible interval [CrI], 0.57-1.89). The intervention failed to reach the pre-specified noninferiority criteria, which the researchers defined as an upper boundary of 95% CrI ≥1.75.

However, also at 18 months, the intervention yielded a rate of 0.0253 in the second co-primary efficacy endpoint vs. 0.0200 in the control arm (risk difference, 0.0053; 95% CrI, –0.0190 to 0.0273), which was noninferior.

The device was associated with a 2.2% rate of early safety events, which was significantly lower than in the initial PROTECT AF study, according to the Holmes and colleagues. This outcome satisfied the pre-specified performance goal.

When a more inclusive definition of adverse events was used, findings from the PREVAIL study still demonstrated lower event rates than PROTECT AF (4.2% vs. 8.7%; P=.004).

A decrease in pericardial effusions requiring surgical repair was reported in the current study, from 1.6% to 0.4% (P=.027). A decrease from 2.9% to 1.5% (P=.36) was reported for those requiring pericardiocentesis. Holmes and colleagues noted that there were few of these events.

“Although noninferiority was not achieved for overall efficacy, event rates were low and numerically comparable in both arms,” they concluded, and added that significant improvements have been seen in procedural safety. “This trial provides additional data that LAA occlusion is a reasonable alternative to warfarin therapy for stroke prevention in patients with [nonvalvular] AF who do not have an absolute contraindication to short-term warfarin therapy.”

Watchman a ‘reasonable alternative’ to warfarin

Randall J. Lee, MD, PhD, of the Cardiovascular Research Institute and the department of medicine at the Institute for Regeneration Medicine at the University of California, San Francisco, noted in an accompanying editorial that the Watchman studies are the first to demonstrate that LAA occlusion may be useful in preventing stroke.

“On the basis of the efficacy data from the initial PROTECT AF trial, the improved mortality data of the 5-year follow-up from PROTECT AF, the improved safety results of the Continued Access PROTECT AF Registry, and the safety data from PREVAIL, an FDA panel recently voted 13 to 1 to approve the Watchman device for use in patients with [nonvalvular] AF,” Lee wrote. “Although the Watchman studies provide the proof of principle that LAA exclusion is effective in preventing stroke in patients with [nonvalvular] AF, LAA device implants should not be considered universally as a substitute for oral anticoagulation therapy.”

Lee highlighted results from several studies that indicated encouraging results for novel anticoagulation drugs such as dabigatran (Pradaxa, Boehringer Ingelheim) and edoxaban (Lixiana, Daiichi Sankyo) in preventing cardioembolic stroke.

“The introduction of LAA exclusion devices and the newer oral anticoagulants offer improved therapies for preventing stroke in patients with [nonvalvular] AF,” Lee wrote. “However, the treatment of the most vulnerable patients who have an increased risk of both ischemic and bleeding events, namely the elderly patient (aged ≥75 years), patients with a history of stroke and those with renal dysfunction, must thoroughly evaluate the benefits and risks of device implantation versus oral anticoagulation therapy. The initial embolic risks and adverse events associated with the Watchman device implantation cannot outweigh the long-term bleeding risks of the newer oral anticoagulation drugs.”

Lee warned that performing LAA occlusion should be approached carefully in elderly patients. He added that the Watchman device has been associated with a 4% rate of thrombus formation, and that long-term surveillance should be instituted for such events.

“PREVAIL attempted to address the learning curve by including new operators who performed the device implantation in nearly 40% of the randomized patients,” Lee wrote. “The safety results between experienced and new operators were similar, suggesting that the sponsor’s training program was adequate. However, the number of new sites was small, and cases were performed in a controlled environment.”

The rollout of the Watchman device should be approached with similar controls in place, according to Lee. “Identifying operators with the necessary skill set to implant the Watchman device will be paramount for the long-term success of LAA exclusion as a treatment for stroke in AF patients,” he wrote.

Lee concluded that despite some of the concerns surrounding long-term effects of implantation, left atrial appendage occlusion is a “reasonable alternative to warfarin for stroke prevention in patients with LAA AF who do not have an absolute contraindication to short-term warfarin.”

For more information:

Holmes DR. J Am Coll Cardiol. 2014;64:1-12.

Lee RJ. J Am Coll Cardiol. 2014;64:13-15.

Disclosure: The researchers report numerous financial disclosures with device and pharmaceutical manufacturers. See the study for a full list of disclosures. Lee is a consultant for SentreHEART and has equity in the company.