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The American College of Cardiology canceled presentation of the PREVAIL study results because the device maker, Boston Scientific, broke the ACC embargo for results. This article was based on interviews conducted in advance of the scheduled presentation. 

SAN FRANCISCO -- Left atrial appendage closure with the Watchman device has gotten safer for stroke prevention in atrial fibrillation, according to results from the PREVAIL, a study designed to allay FDA concerns.

The trial met its primary safety endpoint, finding a 2.2% rate of death, ischemic stroke, systemic embolism, and procedure- or device-related complications requiring surgery or catheter-based intervention that was within the expected upper bound, David R. Holmes, Jr., MD, of the Mayo Clinic in Rochester, Minn., reported here at the American College of Cardiology meeting.

The broader rate of vascular complications, including cardiac perforation and pericardial effusion with tamponade along with the primary composite, was 4.4% -- down from 8.7% in the pivotal PROTECT AF trial (P=0.004).

"I think this takes care of the safety issues," Holmes said in an interview.

The FDA turned down Watchman in lieu of more safety data after the prior trial showed noninferior efficacy to warfarin (Coumadin) but substantially more bleeding and procedure-related complications.

So that made PREVAIL "a win" for the device despite missing one of the two co-primary efficacy endpoints, Michael J. Rinaldi, MD, an interventional cardiologist at Carolinas HealthCare System in Charlotte, N.C., commented in an interview with 麻豆传媒.

The device was similar to warfarin on the efficacy endpoint of ischemic stroke or systemic embolism after the first 7 days post procedure in which most of the excess risk had been seen in the pivotal trial.

The rates were 0.025% versus 0.020%, respectively, which met noninferiority criteria between treatment groups.

On the broader composite of stroke, systemic embolism, and cardiovascular or unexplained death at 18 months, the two groups came out identical in rate (0.064%).

But the wide confidence intervals exceeded the noninferiority threshold, which Holmes chalked up to too small a sample size with only 30 patients in the Watchman group and 58 controls having made it to 18 month follow-up.

Another factor may have been the better than expected performance of warfarin in the control group, he added.

The trial randomized 407 patients overall to left atrial appendage closure with the Watchman device versus long-term warfarin using a complex new type of Bayesian design that boosted the statistical power using the PROTECT AF data for calculating outcome probabilities.

It also was designed to include one-quarter of the operators as new to the procedure, at the behest of the FDA, to confirm it was safe in less experienced hands.

The rate of successful Watchman implantation was similar between new operators and those that were more experienced (93% versus 96%, P=0.256).

Complication rates were actually numerically lower in the less experienced group, though with small numbers and no significant differences.

The researchers cautioned that the results were preliminary.

In a statement, device maker Boston Scientific said it expected the "final fully monitored and adjudicated analysis" within weeks, which it would then take back to the FDA.

When asked about the chances of FDA approval the second time around, Gordon Tomaselli, MD, an electrophysiologist at Johns Hopkins and a past president of the American Heart Association, said there is a really is a role for the device, although not necessarily the one tested in the trial.

Since Watchman has not been shown to be better that warfarin, it shouldn't be considered first-line, he suggested in an interview.

The real role for Watchman should be for patients who can't tolerate anticoagulants -- not just warfarin but also the newer oral agents -- and who score high on the CHAD stroke risk scale, Tomaselli explained. He estimated that perhaps 5% of patients fit those criteria.

PREVAIL included a relatively high-risk cohort with a mean CHADS2 score of 2.6 compared with 2.1 in the PROTECT AF trial, and one that was older with more diabetes and history of stroke or transient ischemic attack.

"This is not a replacement for Coumadin or any of the other new anticoagulants," agreed Rinaldi, who was involved as a site investigator in the trial. But "it may be an attractive alternative for patients at higher risk of bleeding or concerned about bleeding risk."

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