Will Watchman PREVAIL? Positive Study Pulled from ACC Meeting

SAN FRANCISCO, CA—Left atrial appendage (LAA) closure with the Watchman device is a promising alternative to oral anticoagulation therapy for thromboembolic prevention in patients with nonvalvular atrial fibrillation (A-fib), according to a presentation pulled from the annual American College of Cardiology (ACC) Scientific Session/i2 Summit due to early release of data from the manufacturer. Nevertheless, 2 of 3 primary endpoints were met even in the presence of an over-performing control group.

PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device in Patients with Atrial Fibrillation Versus Long-Term Warfarin Therapy) was originally set to headline the opening late breaking clinical trial session on March 9, 2013. On March 4, Boston Scientific (Natick, MA) issued a press release saying that only the acute procedural safety results would be presented, yet on March 6 another press release was issued claiming that all 3 safety and efficacy co-primary endpoints would be available. However, less than 24 hours before the original presentation time, ACC scrapped the entire talk due to an embargo break by Boston Scientific.

Most Promise Shown So Far

For PREVAIL, David R. Holmes, Jr., MD, of the Mayo Clinic (Rochester, MN), and colleagues randomized 407 patients at 41 institutions to either LAA closure with the Watchman device (Atritech, Plymouth, MN; n = 269) or warfarin (n = 138).

The device was implanted more successfully in the trial (95.1%) than in 2 prior Watchman studies: PROTECT AF (90.9%) and the Continued Access Protocol (CAP) registry (94.3%; P = 0.04).

The first primary endpoint (acute occurrence of death, ischemic stroke, systemic embolism, and procedure or device related complications requiring major cardiovascular or endovascular intervention) was met with only 6 total events (2.2%) in the device group through 7 days. Compared with PROTECT AF and the CAP registry, PREVAIL showed decreased composite vascular complications and perforations requiring surgical repair (table 1). There was also a decrease in procedural stroke rates (P = 0.019) and little difference in the outcomes of new vs. experienced operators.

Table 1. PREVAIL Outcomes vs. Previous Studies

 

 
While LAA closure did not show better outcomes in the second primary outcome (composite of stroke, systemic embolism, and cardiovascular/unexplained death at 18 months), there were similar low event rates in both the control and study arms (0.064 vs. 0.064; Rate Ratio 1.07; 95% CI 0.57-1.88).

However, Watchman did show a benefit with regard to the third primary endpoint (ischemic stroke or systemic embolism after 7 days and up to 18 months; 0.0253 vs. 0.0201; Rate Difference 0.0051; 95% CI -0.0191 to 0.0268).

Not Enough Data to Prove Either Safety or Efficacy

In an interview, Steven E. Nissen, MD, of the Cleveland Clinic Foundation (Cleveland, OH), said the ACC made the “right decision” in pulling the presentation from the first late-breaking clinical trial session. The data need to be published, he said, and when it is, “any reasonable journal will ask the right questions.”

He added that if it were up to him, he would have canceled the presentation of PREVAIL earlier in the week when it was rumored that only results from 1 of the 3 primary endpoints would be presented.

Ultimately the data do not pass the “sniff test,” he explained. “The study is not big enough to confirm efficacy,” and 1week safety data are hardly reasonable, he added.

With regard to the approvability of Watchman, Dr. Nissen said, “It’s extremely difficult to see how this device could be approved by the FDA under the circumstances as we currently understand them.” Warfarin vs. placebo had one of the largest treatment effects in the history of medicine, and if a company is to market a device to compete with wafarin, “you have to be able to tell patients that it’s as good as something we already know,” he concluded.

Hesitancy Over ‘Statistical Gymnastics’

Gordon F. Tomaselli, MD, of Johns Hopkins University School of Medicine (Baltimore, MD), said a device like Watchman is attractive because “we have very few other options. One of the things that this study did do, keeping that in the context of PROTECT AF, is demonstrate that the device can be deployed reasonably safely with relatively low short-term primary efficacy complications, lower rates of pericardial effusion, and perforation, but not in a very high-risk population,” he said in an interview.

In his clinical practice, Dr. Tomaselli said about 5% to 10% of his A-fib patients “really do need something” because they have both a high CHADS score and cannot take oral anticoagulants for whatever reason.

With regard to the drama surrounding PREVAIL, he said “it’s something we all need to keep in the back of our heads.” The paper presents some “statistical gymnastics” that are troubling, but Dr. Tomaselli said he attributes the somewhat complicated design of the study to the barrage of questions and scrutiny that PROTECT AF initially received.

“I think this trial was as much a trial about the safety of the deployment of this device as it was about the efficacy,” he said. “I’m convinced that it’s reasonably safe. Is it completely safe? Nope, absolutely not.”

Study Details

The average patient age was 74 years and about two-thirds (67.7%) were male. One-third (33.8%) of patients had diabetes and about one-quarter (27.5%) had a history of stroke.

 

 

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Source:Holmes DR. Final results of randomized trial of left atrial appendage closure versus warfarin for stroke/thromboembolic prevention in patients with non-nalvular atrial fibrillation (PREVAIL). Released prior to: American College of Cardiology Scientific Session/i2 Summit; March 9, 2013; San Francisco, CA.

 

 

 

 

Related Stories:

• PROTECT AF Published: Percutaneous Device Eliminates Need for Warfarin in Many AF Patients
• Watchman Device for LAA Closure Provides Net Clinical Benefit vs. Warfarin in A-fib Patients
• Ongoing Experience Improves Safety for LAA Closure with Watchman Device