Left Atrial Appendage Closure vs Medical Therapy in Atrial Fibrillation

Key Takeaways

• Left atrial appendage closure was not noninferior to physician-directed best medical care for the composite end point.
• A total of 912 adults with atrial fibrillation at high risk for stroke and bleeding were randomized to device therapy or physician-directed medical care, including direct oral anticoagulants when eligible.
• Serious adverse events were common in both groups and were numerically higher with the device strategy.

After a median 3 years of follow-up, left atrial appendage closure was not noninferior to physician-directed best medical care for the primary composite outcome, with first primary end-point events in 155 patients assigned to the device and 127 assigned to medical therapy. The comparison came from a multicenter randomized trial conducted in Germany among adults with atrial fibrillation at high risk for stroke and bleeding. It tested a device-based strategy against physician-directed medical care in an older population with competing thromboembolic and bleeding risks, and it did not meet the prespecified standard for noninferiority.

Participants were assigned to left atrial appendage closure or physician-directed best medical care, including direct oral anticoagulants when eligible. The primary endpoint was a composite of ischemic or hemorrhagic stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death. The primary analysis used a time-to-event noninferiority framework with a prespecified hazard-ratio margin of 1.3 for the treatment comparison. Mean age was 77.9±7.1 years, 38.6% were women, mean CHA2DS2-VASc score was 5.2±1.5, and mean HAS-BLED score was 3.0±0.9. Together, these characteristics describe an older cohort enrolled because of substantial thromboembolic and bleeding risk at baseline.

A total of 912 adults underwent randomization, and the primary analysis included 446 patients in the device group and 442 in the medical-therapy group. Median follow-up was 3 years, with an interquartile range of 1.7 to 4.7 years across the analyzed primary population. First primary endpoint events occurred in 155 device-group patients, or 16.8 per 100 patient-years, and 127 medical-therapy patients, or 13.3 per 100 patient-years. The restricted mean survival time difference was −0.36 years, with a 95% confidence interval of −0.70 to −0.01 and P=0.44 for noninferiority. The prespecified noninferiority criterion for the primary end point was not met.

Serious adverse events occurred in 368 patients, or 82.5%, in the device group and 342 patients, or 77.4%, in the medical-therapy group. They were frequent in both groups and numerically higher with the device strategy during follow-up. The trial was funded by the German Center for Cardiovascular Research. The investigators concluded that left atrial appendage closure was not noninferior to physician-directed best medical care for the composite end point in this population.