A meta-analysis of two randomized trials and two registries found the Watchman device was associated with significant improvements in hemorrhagic stroke, cardiovascular death and nonprocedural bleeding compared with warfarin in patients with nonvalvular atrial fibrillation.
However, patients who received warfarin had fewer ischemic strokes, and the rates of all-cause stroke or systemic embolism were similar between the groups. In March, the FDA approved the Watchman device (Boston Scientific), which is delivered in the cardiac catheterization laboratory and closes the left atrial appendage.
David R. Holmes, Jr., MD, of the Mayo Clinic in Rochester, Minn., and colleagues published their findings online in the Journal of the American College of Cardiology on June 15.
“In patients who have been taking warfarin for a long time and have no problems with it, this device probably won’t be used,” Holmes told Cardiovascular Business. “But in patients in whom you’re concerned as a physician or the patient is concerned as a patient about the need for long-term anticoagulance over the rest of their life, consideration should be given for implantation of devices.”
The FDA approval of the Watchman device was based on results of the PREVAIL (Prospective Randomized Evaluation of the Watchman LAA Closure Device In Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial that compared the device with warfarin for left atrial appendage closure.
In 2009, the FDA failed to approve the device after conclusion of the PROTECT AF (Prospective Randomized Evaluation of the Watchman LAA Closure Device In Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy) trial. The FDA cited a few concerns, including procedural complications, the risk profile of patients and the effect of clopidogrel following implantation.
Holmes et al evaluated data from the PROTECT AF and PREVAIL studies as well as the trials’ registries. The primary efficacy endpoint in each trial was the composite of all-cause stroke, systemic embolization and cardiovascular death.
The analysis included data from 2,406 patients and 5,931 patient-years of follow-up. Of the patients, 1,877 were treated with the Watchman device, and 382 received warfarin.
After a mean follow-up of 2.69 years, the hemorrhagic stroke rates were 0.15 events per 100 patient-years in the Watchman group and 0.96 events per 100 patient-years in the warfarin group. The cardiovascular or unexplained death rates were 1.1 events per 100 patient-years and 2.3 events per 100 patient-years, respectively. In addition, 6 percent of patients in the device group and 11.3 percent of patients in the warfarin group had nonprocedural bleeding.
The all-cause stroke or systemic embolism rates were 1.75 events per 100 patient-years in the device group and 1.87 events per 100 patient-years in the warfarin group, while the rates of ischemic stroke were 1.6 events per 100 patient-years and 0.9 events per 100 patient-years, respectively.
By conducting a meta-analysis, Holmes said he and his colleagues were able to perform frequentist statistical methods, which were easier to understand than the Bayesian statistical approach that was conducted in each of the trials. He added that the meta-analysis allowed the researchers to evaluate changes in patient selection criteria, device performance, safety and efficacy.
The Watchman device is intended for use in patients with nonvalvular atrial fibrillation who are at increased risk for stroke and systemic embolism as assessed by CHADS2 or CHA2DS2-VASc scores. They also must be able to take warfarin because patients who are implanted with the Watchman device are required to take warfarin for 45 days.
Holmes said a trial is being planned in which patients will receive the Watchman device without warfarin or an anticoagulant. He said there are also discussions under way to conduct randomized trials that compare the Watchman device with new oral anticoagulants such as dabigatran (Pradaxa, Boehringer Ingelheim), rivaroxaban (Xarelto, Bayer/Johnson & Johnson) and apixaban (Eliquis, Bristol-Myers Squibb).
“An important piece of information for the field to realize, for the regulatory agencies to realize (and) for the company to realize is that this device is going to be employed and deployed in higher-risk patients,” Holmes said. “There clearly is something that says that not all patients will benefit from this device. If, for example, you have a patient who has carotid artery disease or if you have a patient who has a lot of atheromatous debris in the aorta, using a local device like Watchman is not going to affect the stroke rate.”