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Watchman registry provides reassuring answers on device safety
PARIS – Outcomes were equally good in expert and inexperienced hands.
PARIS – Patients with atrial fibrillation at high stroke risk and a contraindication for oral anticoagulation experienced an 83% reduction in their risk of ischemic stroke and transient ischemic attack during their first year after receiving the Watchman left atrial appendage closure device backed by limited-duration dual-antiplatelet therapy, according to a report from the EWOLUTION registry.
Of 605 participants in the European registry who went on dual-antiplatelet treatment (DAPT) in conjunction with receiving the Watchman device, 39% discontinued DAPT within 3 months and 72% were off DAPT by 6 months. Yet the 1-year rate of ischemic stroke or TIA in the EWOLUTION group was just 1.8%, an 83% relative risk reduction compared with the expected 10.5% rate based on the participants’ mean CHA2DS2-VASc score of 4.6 in the absence of oral anticoagulation, Martin W. Bergmann, MD, said at the annual congress of the European Association of Percutaneous Cardiovascular Interventions.
“Obviously this isn’t a randomized trial. This is just reassuring data that we are going in the right direction in terms of efficacy,” said Dr. Bergmann of Cardiologicum Hamburg, a large German group practice.
Bruce Jancin/Frontline Medical News
Dr. Martin W. Bergmann
However, the ESC guidelines were largely based on randomized trials of the Watchman versus oral anticoagulation, including PREVAIL and PROTECT-AF, showing noninferiority. The safety and efficacy of the device in warfarin-ineligible patients was less well studied at the time the guidelines were formulated. And in fact, such patients are excluded from the Food and Drug Administration’s approved indication, which is specifically for patients judged “suitable for warfarin.”
“This gap is now filled by EWOLUTION. This is a registry that’s as good as it gets. We have all the things in place that you need these days to be able to rely on the outcome data,” according to the cardiologist.
EWOLUTION is a prospective, multicenter, all-comers registry. The EWOLUTION population of AF patients on DAPT was high risk: 89% had a CHA2DS2-VASc score of 3 or more, 31% were at least 80 years old, the mean HAS-BLED score was 2.4, and oral anticoagulation was contraindicated in 84% of participants.
Eighty-seven percent of subjects underwent follow-up transesophageal echocardiography. The imaging study showed the Watchman effectively sealed the left atrial appendage in 99.2% of patients as defined by no leak greater than 5 mm. The echo exam also showed the presence of thrombus on the device at follow-up in 4% of patients, although only 1 of the 22 patients with device thrombus experienced a stroke.
“We can conclude two things from this which are in line with earlier studies. First, the rate of thrombus on the device is equal to the rate reported in the randomized controlled trials, which was also 4%, even if the patients were on warfarin for the first 45 days. And second, these thrombi are not related to stroke,” Dr. Bergmann said.
At the 1-year mark, 71% of patients had switched to a single antiplatelet agent, while 17% remained on DAPT, mainly because of comorbid coronary disease for which DAPT is indicated. Seven percent of patients were on no antithrombotic medications. The remaining 5% were transiently on warfarin or a novel oral anticoagulant.
The 1-year cumulative rate of ischemic stroke or TIA was 1.8%, with no instances of systemic embolism. Of note, there were no hemorrhagic strokes. And of the 11 cases of ischemic stroke, none were fatal and only one was disabling.
“This is a sign that comes also from the PREVAIL trial, that if you have a stroke while on left atrial appendage–closure therapy, most of the time it’s not disabling. It’s much less severe on the modified Rankin Scale than if you’re on oral anticoagulation,” said Dr. Bergmann.
The 1.4% rate of ischemic stroke at 1 year in Watchman recipients represents an 81% reduction in risk compared with the expected 7.5% rate in patients with similar CHA2DS2-VASc scores not on oral anticoagulation. This level of stroke risk reduction is similar to that seen in the pivotal ARISTOTLE trial of apixaban (Eliquis) in a high-risk AF population (Lancet. 2012 Nov 17;380[9855]:1749-58).
Major bleeding occurred in 2.5% of patients. The rate of fatal bleeding was 0.5%. To put that in perspective, the 2.5% major bleeding rate was 52% lower than would be expected based upon similar HAS-BLED scores in patients on warfarin. Still, 2.5% is unacceptably high.
“The major serious adverse event is not pericardial effusion or late device embolization, it’s major bleeding occurring during the time the patient is on DAPT, mostly within the first 3 months. So I think we have to do something about this,” he said.
One possibility worthy of formal study is 3 months of periprocedural NOAC monotherapy. “Maybe even low-dose therapy, like 75 mg of dabigatran [Pradaxa] twice daily. We have an antidote that works nicely [idarucizumab, Praxbind] so I think maybe this is the way to go,” Dr. Bergmann observed.
The ongoing EWOLUTION registry is sponsored by Boston Scientific. Dr. Bergmann is a consultant to that company as well as Bayer AG, Daiichi Sankyo, Eli Lilly, and St. Jude Medical.
