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DENVER -- The Watchman device saved lives and prevented stroke in atrial fibrillation better than warfarin (Coumadin) alone, longer-term results from the PROTECT AF trial showed.

Left atrial appendage closure lowered risk of the composite of stroke, cardiovascular cause of death, or systemic embolism by 40% over the anticoagulant alone at 4 years, which met statistical criteria for superiority, Vivek Reddy, MD, of Mount Sinai School of Medicine in New York City, and colleagues found.

Mortality and hemorrhagic stroke drove the advantage, Reddy reported at a late-breaking presentation here at the Heart Rhythm Society meeting.

The device was associated with a 60% lower risk of death from cardiovascular causes and 34% lower all-cause mortality compared with the warfarin control group, both statistically significant. Hemorrhagic strokes were 85% less likely with the device.

These results are the first demonstration of superiority in any comparison between the two stroke prevention strategies.

Earlier analyses from PROTECT AF showed only non-inferiority. In the newer PREVAIL trial with the device, efficacy endpoints met non-inferiority at best. Safety has come out worse or non-inferior for Watchman versus continued warfarin in the trials.

The updated data "exceeded all expectations," commented David E. Haines, MD, director of the Heart Rhythm Center at William Beaumont Hospital in Royal Oak, Mich.

"Now there is something that may be better for both stroke prevention and overall survival," he explained in an interview with 番茄社区. "It will change the decision making paradigm in these patients and it's a huge population of patients."

"In most cases patients will prefer taking medicine to undergoing an invasive procedure if the results are equivalent. But they will accept the small upfront risk and the morbidity of the invasive procedure for a long-term benefit."

Why did the advantage emerge only at 4 years? It wasn't a shift in relative benefit between the treatment arms, Reddy explained.

"The difference is the confidence intervals have narrowed," he told 番茄社区. "The amount of benefit hasn't really changed. What has changed is our certainty that that number is really true."

In the previously reported PROTECT AF results from a mean 2.3 years of follow-up, the Watchman device group had a 38% lower composite efficacy event risk than those on chronic warfarin.

The randomized trial included 707 patients with nonvalvular atrial fibrillation and at least one risk factor for stroke -- such as prior stroke or transient ischemic attack, congestive heart failure, diabetes, hypertension, or age 75 or older.

Outcomes almost unanimously favored the Watchman device at 4 years:

• For the primary efficacy composite, the rate ratio was 0.60 and event rates 2.3 versus 3.8 per 100 patient-years
• For stroke, the rate ratio was 0.68 and event rates 1.5 versus 2.2 per 100 patient-years
• For systemic embolization, the rate was 0.2 versus 0.0 per 100 patient-years
• For cardiovascular death, the rate ratio was 0.40 and rate 1.0 versus 2.4 per 100 patient-years

All-cause mortality also came in with a rate ratio of 0.66 with the procedure compared with the medical therapy arm (rate 3.2 versus 4.9 per 100 patient-years, P=0.0379).

For the primary safety endpoint, the composite of major bleeding, pericardial effusion, and device embolization came out with a rate ratio of 1.17 favoring chronic warfarin but without a significant difference, unlike in the earlier results.

Pericardial tamponade requiring treatment occurred in 4.8% of patients, resulting in extended hospitalization but no deaths or long-term disability.

The rate went down with experience, from 6.3% in the first half of the cohort to 3.7% in the second half, akin to what was seen in PREVAIL versus PROTECT AF.

The results didn't appear to be due to the antithrombotic regimen accompanying the Watchman device, which included warfarin plus aspirin for 45 days then clopidogrel and aspirin to month 6 and aspirin continued thereafter, Reddy noted in a secondary analysis.

Efficacy appeared similar in the subgroup of secondary prevention patients as in the overall cohort.

Reddy cautioned that the results cannot be extrapolated to the newer anticoagulants or to other methods or devices for closing the left atrial appendage.

But he and Haines agreed that the FDA is likely to look favorably on the new data from PROTECT AF and PREVAIL when the device again goes up for approval, which is anticipated to happen soon.

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