Key Points:
- The CLOSURE AF study compared catheter-based left atrial appendage closure with physician-directed standard medical care (including timely anticoagulant blood thinning when eligible) in patients with atrial fibrillation at high risk for stroke and bleeding.
- In patients with atrial fibrillation (AF) at high risk for both stroke and bleeding, catheter-based left atrial appendage (LAA) closure did not achieve noninferiority to physician-directed best medical care.
- Despite high procedural success and low complication rates, adverse events were driven by major bleeding and cardiovascular death, emphasizing the importance of careful patient selection and post-procedure management.
The CLOSURE-AF trial (NCT03463317), presented at the American Heart Association Scientific Sessions 2025, was a large, randomized study designed to compare LAA closure with optimal medical therapy in patients with AF and both high thromboembolic and hemorrhagic risk. The prospective, multicenter, event-driven trial randomized 888 participants (mean CHA₂DS₂-VASc ≥2, HAS-BLED ≥3 or prior major bleed) at 46 German centers to undergo percutaneous LAA closure (n=446) or receive physician-directed best medical care (n=442), including oral anticoagulation when feasible. The primary composite endpoint was stroke, systemic embolism, cardiovascular or unexplained death, or major bleeding (BARC ≥3), tested for noninferiority with a margin of 1.3.
Over a median follow-up of three years, the composite primary endpoint occurred more frequently in the LAA closure group (16.83% vs 13.27%; adjusted HR 1.28, 95% CI 1.01–1.62; p=0.44 for noninferiority). In per-protocol analysis, rates remained higher with LAA closure (16.55 vs 12.50 events per 100 patient-years; HR 1.34, 95% CI 1.04–1.72). Procedural success was excellent (98.3%), with 4.3% experiencing major bleeding within seven days and 1.2% pericardial tamponade—lower than historical rates. Only 4.8% of patients had residual leaks, and embolization occurred in one case. However, major bleeding and cardiovascular deaths were more frequent following LAA closure, offsetting any ischemic stroke reduction.
Principal investigator Dr. Ulf Landmesser (Charité University Medicine Berlin) emphasized that the findings challenge assumptions about the net benefit of device-based stroke prevention in extreme-risk populations. “Our findings indicate that standard physician-directed medical care, including blood thinners for eligible patients, remains a valid management option for those older patients with irregular heartbeat who are at very high risk for stroke and bleeding” he said. The results suggest that while LAA closure remains a viable strategy for select patients unable to tolerate anticoagulation, its use in those with both high ischemic and bleeding risk should be approached with caution. Ongoing studies such as CHAMPION-AF are expected to further define the role of LAA occlusion in broader AF populations.