May 10th, 2013

Encouraging 4-Year Results for Boston Scientific’s Watchman Device in AF Patients

Encouraging long-term results from the PROTECT AF trial comparing the Watchman left atrial appendage closure device to warfarin in atrial fibrillation (AF) patients were presented yesterday at the Heart Rhythm Society meeting in Denver.

Previously the main results of the trial, published in the Lancet, demonstrated that the Watchman was noninferior to warfarin, but the total number of events in the trial was small. In addition, there were more safety problems, as might be expected, in the early days after implantation. The FDA required the company to perform a confirmatory trial. That trial, PREVAIL, has been the subject of considerable controversy. Now, long-term followup of PROTECT AF may help better understand the risks and benefits of the device.

Vivek Reddy presented 4-year followup results from PROTECT AF. The primary efficacy endpoint — the combined rate of all stroke, cardiovascular, or unexplained death and systemic embolism — occurred in 2.3% of the device group versus 3.8% of the warfarin group (RR 0.60, CI 0.41-1.05).

Death from any cause occurred in 3.2% of the device group versus 4.8% of the warfarin group (HR 0.66, CI 0.45-0.98, p=0.0379). The cardiovascular death rate was 1% in the Watchman group versus 2.4% in the warfarin group (HR 0.40, p=0.0045).

In the initial publication of the trial there was an increased number of events in the primary safety endpoint in the Watchman group. With longer followup that difference is no longer significant. There were 60 events per 1666.2 patients years in the Watchman group versus 27 events per 878.2 patient years in the warfarin group (RR 1.17, 0.78-1.95, p=0.196). Twenty-two Watchman patients had pericardial tamponade. Although these patients required extended hospitalization there were no deaths or long-term disabilities in this group. Reddy also reported that due to the greater experience of the operators, safety events were greatly reduced (from 6.3% to 3.7%) after the first half of the trial.

“This is a significant development because for the first time we were able to demonstrate that the WATCHMAN device was superior to warfarin for both primary efficacy and also mortality,” said Reddy, in a Boston Scientific press release. “This has tremendous upside potential for patients. In the PROTECT AF trial, LAA closure with the WATCHMAN device demonstrated the potential for a device-based approach to reduce the risk of stroke in AF patients. As clinicians, we often feel uncomfortable with life-long systemic anticoagulation therapy in patients because of an increased risk of falls and bleeding. The four-year data provide additional support for LAA closure as a potential viable long-term alternative to chronic warfarin therapy for patients to reduce the risk of stroke.”

Sanjay Kaul said that a claim of superiority should be regarded with caution: “While the total number of events (information size) has increased from 39 to 73, which explains the narrowing of the credible (confidence) intervals, caution is warranted before ENTHUSIASTICALLY claiming superiority.”

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