Abstract Body (Do not enter title and authors here): Background: Percutaneous catheter-based left atrial appendage (LAA) closure is a potential alternative to oral anticoagulation for stroke prevention in patients with atrial fibrillation (AF), especially in patients at high bleeding risk. The effectiveness and safety of LAA closure in patients with AF at high risk of stroke (CHA₂DS_2-VASc Score ≥ 2) and high risk of bleeding compared to best medical care including non-vitamin K antagonist oral anticoagulants [NOAC] needs to be further investigated.
Methods/Design: The prospective, multicenter, randomized clinical Left atrial appendage CLOSURE in patients with Atrial Fibrillation at high risk of stroke and bleeding compared to medical therapy (CLOSURE-AF) trial (NCT03463317) compares catheter-based LAA closure with the Watchman FLX or Amplatzer Amulet device to best medical care (including NOAC therapy if considered eligible) in patients with AF at high risk of stroke and with either a history or risk of major bleeding (i.e., prior BARC 3 a-c, chronic kidney disease [eGFR 15-29 ml/min/1.73 m²], HAS-BLED≥3), or any recurrent bleeding making chronic anticoagulation not feasible. The primary endpoint is time to a composite of first stroke, systemic embolism, cardiovascular or unexplained death or major bleeding (BARC 3-5). All clinical endpoints are adjudicated by a clinical endpoint committee (CEC). Secondary endpoints include components of the primary outcome and all-cause mortality. The primary efficacy analysis is performed in the intention-to-treat population using Cox regression models. The study is designed to test non-inferiority of percutaneous LAA closure as compared to best medical care in patients with atrial fibrillation at high bleeding risk, with the option to subsequently assess superiority.
Results: The first patient in the CLOSURE-AF trial was enrolled in March 2018. After a second blinded interim analysis with sample size recalculation the complete study cohort of n=912 patients had been enrolled in 46 sites in Germany by April 2024. The last patient completed the trial in November 2024. Final trial results will be available at the time of presentation in case of acceptance.
Conclusion: CLOSURE-AF represents the largest clinical study thus far to compare effectiveness and safety of LAA occlusion with best medical care in patients with AF at high risk of stroke and bleeding. The trial results will inform the clinical use of catheter-based LAA closure in this patient population.