The CLOSURE-AF (Catheter-Based Left Atrial Appendage Closure in Patients With Atrial Fibrillation at High Risk of Stroke and Bleeding as Compared With Best Medical Therapy) trial found that, among patients with atrial fibrillation (AF) at high risk for both stroke and bleeding, catheter-based left atrial appendage occlusion (LAAO) failed to demonstrate noninferiority compared with physician-directed medical therapy for the composite outcome of stroke, systemic embolism, major bleeding, or cardiovascular or unexplained death.¹

CLOSURE-AF was a pragmatic, prospective, multicenter randomized controlled trial conducted across 42 centers in Germany. A total of 888 patients (mean age, 78 years) were included in the intention-to-treat analysis (446 LAAO vs. 442 medical therapy); 85% of patients in the medical arm received direct oral anticoagulants (DOACs). The cohort was at substantial thromboembolic and bleeding risk (mean CHA₂DS₂-VASc score, 5.2; HAS-BLED score, 3.0).

At a median follow-up of 3 years, the primary endpoint occurred more frequently in the LAAO group (16.8 vs. 13.3 events per 100 patient-years), with a restricted mean survival time difference of -0.36 years (95% confidence interval, -0.70 to -0.01; p = 0.44 for noninferiority). Stroke rates were similar between groups (2.6 vs. 2.7 per 100 patient-years), and no reduction in major bleeding was observed despite avoidance of long-term anticoagulation, an important finding given that bleeding reduction is a primary rationale for LAAO in this population. Serious adverse events were more frequent in the device arm (82.5% vs. 77.4%), and periprocedural complications occurred in 5.7%, highlighting an early procedural risk associated with device implantation. Together, these findings suggest that potential long-term benefits of LAAO may be offset by early procedural and postprocedural risks in this high-risk population.¹

Noninferiority of LAAO compared with DOACs has been demonstrated in the past.² CLOSURE-AF specifically enrolled patients at high risk for both stroke and bleeding, a population not directly represented in prior trials.

Several limitations merit consideration. The CLOSURE-AF trial was not powered to detect differences in individual endpoint components, was conducted exclusively in Germany (predominantly White cohort), and underwent two sample size reductions based on interim analyses. From a clinical perspective, CLOSURE-AF reinforces the importance of careful patient selection for LAAO and highlights the continued central role of DOAC therapy in eligible patients. Trials such as the recently published CHAMPION-AF (Watchman Flx versus NOAC for Embolic Protection in the Management of Patients With Non-Valvular Atrial Fibrillation) and ongoing CATALYST (Amplatzer Amulet LAAO vs. NOAC) study are expected to refine which subgroups may benefit from a device-based approach.^3,4

References

1. Landmesser U, Skurk C, Kirchhof P, et al. Left atrial appendage closure or medical therapy in atrial fibrillation. N Engl J Med. 2026;394(13):1270-1280. doi:10.1056/NEJMoa2513310
2. Osmancik P, Herman D, Neuzil P, et al. Left atrial appendage closure versus direct oral anticoagulants in high-risk patients with atrial fibrillation. J Am Coll Cardiol. 2020;75(25):3122-3135. doi:10.1016/j.jacc.2020.04.067
3. Doshi SK, Kar S, Nair DG, et al. Left atrial appendage closure or anticoagulation for atrial fibrillation. N Engl J Med. 2026;394(21):2083-2094. doi:10.1056/NEJMoa2517213
4. Reddy VY, Hylek E, Camm AJ, et al. Left atrial appendage occlusion versus NOACs in patients with atrial fibrillation: rationale and design of the CATALYST trial. Am Heart J. 2026;296:107367. doi:10.1016/j.ahj.2026.107367