Percutaneous left atrial appendage closure has been proposed as an alternative to anticoagulation in patients with atrial fibrillation and high bleeding risk; however, comparative evidence versus contemporary medical therapy (including DOACs) in this specific population has been limited. In this context, the CLOSURE-AF study was a multicenter, randomized, open-label clinical trial with blinded event adjudication, conducted across 42 centers in Germany, including patients with atrial fibrillation at high risk of stroke (CHA₂DS₂-VASc ≥2) and bleeding (HAS-BLED ≥3 or relevant prior bleeding).
A total of 912 patients were randomized, of whom 888 were included in the intention-to-treat analysis: 446 assigned to left atrial appendage closure and 442 to physician-directed medical therapy (85.1% receiving DOACs). The mean age was 77.9±7.1 years, 38.6% were women, with a mean CHA₂DS₂-VASc score of 5.2±1.5 and a HAS-BLED score of 3.0±0.9. Median follow-up was 3 years (IQR 1.7–4.7). The primary endpoint was a composite of stroke (ischemic or hemorrhagic), systemic embolism, major bleeding (BARC ≥3), or cardiovascular or unexplained death. Secondary endpoints included the individual components of the primary endpoint and all-cause mortality.
During follow-up, the primary endpoint occurred in 155 patients in the LAAO group (16.8 events per 100 patient-years) and in 127 patients in the medical therapy group (13.3 per 100 patient-years), with a restricted mean survival time difference of −0.36 years (95% CI −0.70 to −0.01; p=0.44 for non-inferiority), thus failing to demonstrate non-inferiority of left atrial appendage closure. Regarding individual components, stroke occurred in 27 patients in each group (2.6 vs 2.7 per 100 patient-years), systemic embolism in 3 vs 1 patients (0.3 vs 0.1), major bleeding in 70 vs 61 patients (7.4 vs 6.2), and cardiovascular or unexplained death in 99 vs 81 patients (9.5 vs 7.7), respectively, with no statistically significant differences observed between groups.
All-cause mortality was 155 vs 141 patients (14.8 vs 13.5 per 100 patient-years; RMST difference −0.13 years; 95% CI −0.48 to 0.21). The rate of serious adverse events was high and comparable between groups (82.5% vs 77.4%, with no formal superiority analysis reported). In the device group, procedural success was 98.3%, with periprocedural complications occurring in 5.7%.
Conclusion: Left atrial appendage closure fails to demonstrate non-inferiority versus medical therapy in high-risk atrial fibrillation patients
In patients with atrial fibrillation at high risk of stroke and bleeding, percutaneous left atrial appendage closure did not demonstrate non-inferiority compared with contemporary optimal medical therapy in terms of the composite endpoint of thromboembolic events, major bleeding, or cardiovascular death at 3 years. These findings reinforce that, in this population, pharmacological therapy remains the comparative standard, and that the indication for LAAO should be carefully individualized.
Original Title: Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation.
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