Clinical question: Is there a favorable risk-benefit ratio for left atrial appendage closure (LAAC) compared to warfarin for prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation?
Background: LAAC with the WATCHMAN device was shown to be noninferior to warfarin for the prevention of stroke, systemic embolism, and cardiovascular death in nonvalvular atrial fibrillation in two trials: PROTECT AF and PREVAIL. Further efficacy concerns were raised following routine regulatory filings, leading to the need for continued evaluation.
Study design: Meta-analysis.
Setting: Patient-level data were combined and analyzed from the PROTECT AF and PREVAIL trails and two nonrandomized registries of LAAC with the WATCHMAN device: the Continued Access PROTECT AF registry (CAP) and the Continued Access to PREVAIL registry (CAP2).
Synopsis: A total of 2,406 patients were enrolled from all four data sets from 2005-2014. Of those, 1,877 were treated with the WATCHMAN device and 382 were treated with warfarin. Annualized risk of stroke if untreated with anticoagulation for all patients was 5.7% to 7.6%, indicating that all were eligible to be treated with warfarin. Ninety percent of patients had moderate to high risk of bleeding. Analysis showed that LAAC was noninferior to warfarin for stroke, systemic embolism, and cardiovascular death.
A slight increase in ischemic stroke in the LAAC group was counterbalanced by the significant reduction in hemorrhagic stroke in the LAAC group versus the warfarin group. Cardiovascular deaths were significantly fewer in the LAAC cohort; all-cause mortality favored LAAC but did not reach statistical significance. There was also a significant reduction in nonprocedure-related major bleeding in the LAAC group. Limitations of this study include the limited number of patients treated with warfarin and lack of comparison to new oral anticoagulants (NOACs).
Bottom line: Patients with increased stroke risk from nonvalvular atrial fibrillation treated with the WATCHMAN device for LAAC have significant reductions in hemorrhagic stroke, cardiovascular death, and nonprocedure-related major bleeding, but slightly increased risk of ischemic stroke compared to those treated with warfarin.
Citaiton: Holmes DR Jr, Doshi SK, Kar S, et al. Left atrial appendage closure as an alternative to warfarin for stroke prevention in atrial fibrillation: a patient-level meta-analysis. J Am Coll Cardiol. 2015;65(24):2614-2623.