Percutaneous Left Atrial Appendage Closure for Stroke Prophylaxis in Patients with Atrial Fibrillation: 2.3 Year Follow-Up of the PROTECT AF Trial

Background —The multicenter PROTECT AF study was conducted to determine whether percutaneous left atrial appendage (LAA) closure with a filter device (Watchman) was noninferior to warfarin for stroke prevention in atrial fibrillation (AF). Methods and Results —Patients (n = 707) with nonvalvular AF and at least one risk factor (age > 75, hypertension, heart failure, diabetes or prior stroke/TIA) were randomized to either the Watchman device (n = 463) or continued warfarin (n = 244) in a 2:1 ratio. After device implantation, warfarin was continued for ~45 days, followed by clopidogrel for 4.5 months and lifelong aspirin. Study discontinuation rates were 15.3% (71/463) and 22.5% (55/244) for the Watchman and warfarin groups respectively. The time in therapeutic range for the warfarin group was 66%. The composite primary efficacy endpoint included stroke, systemic embolism and cardiovascular death, and the primary analysis was by intention-to-treat. After 1,588 patient-years of follow-up (mean 2.3±1.1 years), the primary efficacy event rates were 3.0% and 4.3% (percent per 100-patient years) in the Watchman and warfarin groups, respectively (RR = 0.71, 95% CI 0.44-1.30%/y), meeting the criteria for non-inferiority (probability of non-inferiority > 0.999). There were more primary safety events in the Watchman group (5.5%/y, 95% CI 4.2-7.1%/y) than in the control group (3.6%/y; 95% CI 2.2-5.3%/y; RR 1.53, 95% CI 0.95-2.70). Conclusions —The "local" strategy of LAA closure is noninferior to "systemic" anticoagulation with Warfarin. PROTECT AF has, for the first time, implicated the LAA in the pathogenesis of stroke in AF. Clinical Trial Registration Information —Clinicaltrials.gov; Unique Identifier: NCT00129545.