DENVER – Left atrial appendage closure using the Watchman device is as effective as warfarin in preventing strokes in patients with atrial fibrillation, but the strokes in Watchman recipients are 55% less likely to be disabling, according to a meta-analysis of 5-year outcomes in the PREVAIL and PROTECT AF randomized trials.
The device therapy showed additional advantages over warfarin: significantly reduced risks of mortality, non–procedure-related major bleeding, and hemorrhagic stroke, Saibal Kar, MD, reported in presenting the results of the meta-analysis at the Transcatheter Cardiovascular Therapeutics annual educational meeting.“This is not a first-line therapy. But we know there is a large number of patients who cannot tolerate long-term anticoagulation. And this is the ideal therapy for stroke prophylaxis in that group of patients,” according to Dr. Kar, director of interventional cardiac research at Cedars-Sinai Medical Center in Los Angeles.
“We have prevailed,” he declared, referring to device safety concerns that arose early on and have since been laid to rest.
The patient-level meta-analysis of 5-year outcomes included 1,114 patients with atrial fibrillation who were randomized 2:1 to the Watchman device or warfarin, with 4,343 patient-years of follow-up. This was a fairly high–stroke risk population, with CHA2DS2-VASc scores in the 3.6-3.9 range, and 40% of patients aged 75 years or more. At baseline, 23% of subjects had a history of stroke or transient ischemic attack.
At 5 years’ follow-up, the composite endpoint of all stroke or systemic embolism was the same in the two study arms. However, the rate of hemorrhagic stroke was 80% lower in the Watchman group, the risk of disabling or fatal stroke was reduced by 55%, the rate of cardiovascular or unexplained death was 41% lower, all-cause mortality was reduced by 27%, and postprocedure major bleeding was 52% less frequent in the device therapy group. All of these differences achieved statistical significance, the cardiologist reported at the meeting sponsored by the Cardiovascular Research Foundation.
On the downside, the rate of ischemic stroke trended higher in the Watchman group, although the 71% increase in relative risk didn’t achieve statistical significance (P = .08). Dr. Kar asserted that this unhappy trend was a statistical fluke resulting from a low number of events and an implausibly low ischemic stroke rate of 0.73% per year in the warfarin group.
“This is the lowest rate of ischemic stroke in any study of warfarin. In fact, if this was the ischemic stroke rate in any of the NOAC [novel oral anticoagulant] studies, none of those drugs would actually have been approved. Why did we get such an implausibly low ischemic stroke rate? It’s a function of lower numbers and larger confidence intervals,” he said.
Gregg W. Stone, MD, who moderated the discussion panel at the late-breaking clinical trial session, advised Dr. Kar to be less defensive about the ischemic stroke findings.
“I think we have to be a little less apologetic for the great outcomes in the warfarin arm in PREVAIL. We do these randomized trials, and we get what we get,” said Dr. Stone, professor of medicine at Columbia University in New York.
Stephen G. Ellis, MD, said he was particularly impressed with the reduced rate of disabling stroke in the Watchman group.
“Severity of stroke is important. I hadn’t seen that data before,” commented Dr. Ellis, professor of medicine and director of the cardiac catheterization laboratory at the Cleveland Clinic. “The overall message, I think, is that for the patients who would have been candidates to be enrolled in these trials, the device seems to be quite worthwhile. I take note of the overall benefit in terms of cardiovascular death and all-cause death.”
Robert J. Sommer, MD, said that in patients with high CHA2DS2-VASc scores and previous bleeding on oral anticoagulants, the new data show that the Watchman “is a no-brainer. The patients all want it, the physicians all want it. It’s a very easy decision to make.”
“But you get into other groups who may potentially be interested in the device – particularly the younger patients who are very active and don’t want to be on anticoagulation – I think the ischemic stroke rate in the device arm trending to be higher is a problem for them. And it’s certainly going to be a problem for their physicians. But as we go on, I think with further studies we’ll see expanded indications. Patients with CAD who potentially would need triple therapy – that’s a nice population to study in this area. We’ll also be seeing data on other devices that may have different ischemic stroke rates,” said Dr. Sommer, director of invasive adult congenital heart disease at Columbia University Medical Center.
“I find this data extraordinarily helpful as I think about my conversations with patients about stroke prevention,” said Brian K. Whisenant, MD, medical director of structural heart disease at the Intermountain Medical Center Heart Institute in Salt Lake City.
“I tell them we think of oral anticoagulants as first-line therapy based on a stroke rate of 1% per year or less in most datasets. The data for the Watchman device has been very consistent in that we have a stroke rate that’s a little bit higher, at 1.3%-1.8% per year. And we have extensive data for predicting the stroke rate in the absence of oral anticoagulation: In most of our patients, that rate is in excess of 5% per year. So while the Watchman device may not provide the absolute reduction in ischemic stroke rate that oral anticoagulants do, a stroke rate of less than 2% is a whole lot better than no therapy for many of these patients,” the cardiologist said.
Martin B. Leon, MD, opined that the ischemic stroke data cannot be explained away. But he added that the totality of the meta-analysis data gives him confidence that this is the appropriate treatment in these patients.
“It does leave open the question of whether we can do better with ischemic strokes. Some people are suggesting that maybe adjunctive pharmacotherapy – perhaps a low-dose NOAC – may be a reasonable option in some patients to get even better results. That’s something I believe is open for discussion,” said Dr. Leon, professor of medicine at Columbia University and director of the Center for Interventional Vascular Therapy at New York-Presbyterian/Columbia University Medical Center, New York.
Dr. Stone summed up: “There’s uniformity among the panel that there may be a slightly lower ischemic stroke rate with oral anticoagulation, and the NOACs probably provide some additional benefit, with an additional 50% reduction in hemorrhagic stroke, compared to warfarin. But that being said, I believe that left atrial appendage closure with the Watchman is the viable and now clearly safe approach for patients with any sort of contraindication or strong desire to avoid oral anticoagulation.”
The PREVAIL and PROTECT AF trials and meta-analysis were sponsored by Boston Scientific. Dr. Kar reported receiving research grants from and serving as a consultant to that company as well as Abbott Vascular.
Simultaneously with Dr. Kar’s presentation at TCT 2017, the findings were published online in the Journal of the American College of Cardiology.
SOURCE: Reddy VY et al. TCT 2017; J Am Coll Cardiol. 2017 Nov 4. pii:S0735-1097(17)41187-9. doi: 10.1016/j.jacc.2017.10.021.