Four-year follow-up data from the PROTECT AF clinical trial demonstrated that Boston Scientific Corp.’s Watchman left atrial appendage (LAA) closure device for stroke prevention in atrial fibrillation patients is statistically superior to warfarin for the primary endpoint of cardiovascular death, all-cause stroke and systemic embolization. But the company is highlighting secondary endpoint analyses showing that Watchman reduces both cardiovascular death and all-cause death compared to warfarin.

The new PROTECT AF results were presented at the Heart Rhythm Society Scientific Sessions May 9 by electrophysiologist Vivek Reddy from Mount Sinai Hospital in New York.

“To see a mortality benefit in a trial like this – with only 700 patients – is very surprising, and I think that’s something that physicians and regulatory officials are going to look at,” Reddy told “The Gray Sheet.” “Before this presentation, we could say [to patients] ‘We can get you off of warfarin with this device strategy and we can do that with statistically equivalent or perhaps better outcomes.’ But with the new results, physicians can tell Watchman candidates the device reduces the risk of all-cause mortality by about one third.

The 59-center PROTECT AF trial enrolled 707 patients with non-valvular atrial fibrillation who were eligible for warfarin therapy and had certain stroke risk factors. Patients were randomized two-to-one to Watchman or warfarin therapy, the standard of care. For the primary composite efficacy endpoint of cardiovascular death, stroke and systematic embolization, the event rates were 2.3 percent and 3.8 percent in the Watchman and control groups, respectively – a 40 percent risk reduction.

For the secondary endpoint of all-cause mortality, the event rates were 3.2 percent in the Watchman group and 4.8 percent in the control group, representing a 34 percent risk reduction in all-cause mortality (p=0.0379). For death from cardiovascular causes only, the rates were 1 percent in the Watchman group and 2.4 percent in the control group – a 60 percent risk reduction (p=0.0045).

Kenneth Stein, chief medical officer of Boston Scientific’s cardiac rhythm management division told “The Gray Sheet” that the results will change the conversation between physicians and patients. “There are very few things in medicine that are associated with a 34 percent reduction in total mortality – death from any cause. That is a big-deal result. It certainly enables you, as you’re talking to a patient who is trying to decide between their options, to give them much more confidence and a better sense of security if they elect to go this route.”

Boston Scientific Prepares For Watchman Launch

The presentation of the long-term results is a major milestone in the journey that began when Boston Scientific took over the Watchman development program as part of a $375 million acquisition of Atritech Inc.in early 2011. (See Also see "Boston Scientific Buys Atritech For Watchman Stroke Prevention Device" - Medtech Insight, 24 January, 2011..)

Boston Scientific CEO Michael Mahoney told “The Gray Sheet,” “We’re super proud of the trial results that Dr. Reddy presented [at the HRS meeting]. This is a device that we acquired a number of years ago with the promise that the results would turn out like they did and they have. … We’re excited about the impact it’s going to have on patients because it’s not often that you have a superiority endpoint delivered like that.”

The company plans to submit the data as part of a PMA filing to FDA by the end of the second quarter of 2013, Mahoney said. The submission will also include the final results of PREVAIL, an 88-patient study that showed that adverse events decrease as the physicians implanting the devices gain more experience (See Also see "Boston Scientific Says PREVAIL Results Affirm Safety of Watchman LAA Anti-Stroke Device" - Medtech Insight, 18 March, 2013..) The firm will also submit six-year follow-up data from some patients in the PROTECT AF pilot study, results from a 150-patient ASA Plavix contraindication registry in Europe, and data from the Watchman continued access protocol registry results.

Boston Scientific first submitted Watchman for FDA approval in 2007. The agency’s advisory panel voted 7-5 in favor of approving Watchman based on earlier results from PROTECT AF showing that left-atrial appendage closure with Watchman was non-inferior to long-term anticoagulation medication. After that panel meeting, FDA asked Boston Scientific to conduct PREVAIL to resolve doubts about the relatively high rate of pericardial effusions and procedure related strokes observed during early experiences with the device. (See Also see "Panel Endorses Atritech Watchman Stroke-Prevention Device In Close Vote" - Medtech Insight, 27 April, 2009..)

Reddy said, “The concern after the initial data from PROTECT AF was, ‘Yes, it’s a non-inferior outcome. However, the set-point for declaring non-inferiority was relatively high.’ That was a concern” in light of the relatively high complication rates during the early experience with the device.

“The only way you can really declare non-inferiority is to have superiority,” he said. “This is 2,600 patient-years of follow-up and not only did the curves not narrow, but they continued to widen, and the initial point-estimate of about 30 to 40 percent risk reduction with the Watchman continued to stay the same and the confidence intervals came down to the point where it’s not just non-inferior but superior.”

Recalling the lessons from the early experience with Watchman, Reddy said, “If and when this device gets approved, I think that Boston Scientific will be very careful with the rollout and making sure there is good [physician] training.”

Mahoney said that, in Europe, Watchman is implanted by both electrophysiologists and interventional cardiologists, and the company plans to market it to both of those specialties in the U.S.

“The good news for Boston Scientific is that we are a strong EP player and we’re very strong in interventional cardiology. We’re seeing about a 50/50 split [between electrophysiologists and interventionalists] in terms of use of the device, and it’s really determined independently at the hospital level between the electrophysiologist and interventional cardiologists or a combination of both. But we have the commercial reach and the clinical capability to provide training, as importantly, to support both.”

PROTECT AF Results Show Long-Term Efficacy Of Watchman LAA Closure Device

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