Physicians traditionally view Left Atrial Appendage Closure as a critical alternative for stroke prevention in atrial fibrillation (AF) patients who cannot tolerate long-term anticoagulation. However, results from the multicenter CLOSURE-AF randomized trial suggest a need for caution. The study specifically examined whether this interventional strategy could match the efficacy and safety of physician-directed medical care in high-risk populations. Consequently, the findings published in the New England Journal of Medicine provide new perspectives on managing patients with elevated stroke and bleeding risks.

Evaluating Left Atrial Appendage Closure Outcomes

Researchers conducted this prospective study across 46 centers in Germany, focusing on 912 patients with nonvalvular AF. These individuals carried a high risk for both stroke and major bleeding, characterized by mean CHA2DS2-VASc and HAS-BLED scores of 5.2 and 3.0, respectively. Furthermore, the trial compared catheter-based Left Atrial Appendage Closure to optimized medical therapy. This medical arm primarily included direct oral anticoagulants (DOACs) for eligible participants. In contrast, the interventional group received various CE-marked devices followed by short-term antithrombotic therapy.

Notably, the results indicated that the device-based approach was not noninferior to medical management. Specifically, the primary composite endpoint occurred in 16.8 patients per 100 patient-years in the device group. Similarly, the medical-therapy group recorded an incidence of 13.3 per 100 patient-years. Therefore, the hazard ratio reached 1.28, which failed to meet the predefined noninferiority margin of 1.3. Additionally, serious adverse events were slightly more frequent in the device group than in the medical therapy group.

Ultimately, these findings highlight the impressive performance of contemporary medical therapy. Even in patients previously deemed difficult to treat, modern DOAC-based regimens proved highly effective. While procedural success for the device reached nearly 98%, the overall clinical benefit did not surpass standard care. Moreover, these data suggest that optimized medical management remains the preferred strategy for high-risk AF patients unless a clear contraindication to anticoagulation exists. Physicians should consequently weigh individual risks carefully before recommending procedural interventions over drug therapy.

Why did the CLOSURE-AF trial fail to show noninferiority?

The trial failed because the rate of primary endpoint events was numerically higher in the device group than in the medical therapy group. Specifically, contemporary medical care using DOACs proved more effective than anticipated, making it difficult for the closure procedure to achieve the noninferiority threshold.

Which patients were included in this study?

The study included elderly patients with atrial fibrillation who had a high risk of stroke and a history of major bleeding. Most participants in the medical therapy arm received DOACs. The average age of the cohort was approximately 78 years, representing a truly high-risk demographic in clinical practice.

Disclaimer: This content is for informational and educational purposes only. It does not constitute professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

1. Landmesser U et al. Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation. N Engl J Med. 2026 Mar 18. doi: 10.1056/NEJMoa2513310. PMID: 41849741.


2. Reddy VY, et al. 5-Year Outcomes After Left Atrial Appendage Closure: From the PREVAIL and PROTECT AF Trials. J Am Coll Cardiol. 2017;70(24):2964-2975.


3. Boersma LV, et al. Global Heart: Clinical Outcomes of the Watchman Device in a Real-World Patient Population. J Am Coll Cardiol. 2016;68(17):1851-1861.