Why LAAC Failed to Beat Medical Therapy in High-Risk AF

Recent trials have challenged the widespread use of left atrial appendage closure as a direct substitute for oral anticoagulation. Specifically, the highly anticipated CLOSURE-AF trial evaluated whether this mechanical intervention could match contemporary drug regimens in vulnerable patients. However, the trial demonstrated that the procedure failed to achieve noninferiority. Consequently, clinicians must carefully reconsider patient selection.

The Gap in High-Risk Clinical Data

Indeed, previous studies suggested that mechanical closure performed comparably to traditional anticoagulation. In contrast, those older trials primarily enrolled low-to-moderate risk individuals. Consequently, we lacked robust data for patients facing exceptionally high risks of both stroke and bleeding. Subsequently, the CLOSURE-AF investigators randomized 912 adult patients to either device intervention or standard medical therapy to resolve this uncertainty. Furthermore, the medical-therapy group predominantly received modern direct oral anticoagulants.

When Left Atrial Appendage Closure Falls Short

Notably, the study population had a mean age of nearly 78 years. Additionally, these patients had remarkably high baseline risk scores. Specifically, the average CHA2DS2-VASc score was 5.2, and the average HAS-BLED score was 3.0. Ultimately, the trial did not show noninferiority for the primary composite endpoint. Moreover, serious adverse events occurred in 82.5% of the device group. Thus, these findings suggest that standard medical care remains superior for this complex demographic.

Clinical Implications for Indian Practitioners

Overall, this trial reinforces that mechanical closure is not a one-size-fits-all solution. For instance, perioperative complications and post-procedure antithrombotic needs heavily influence clinical success. Consequently, Indian clinicians must balance these risks when designing treatment plans. We must recognize that medical therapy often provides safer and more predictable outcomes for older, multimorbid patients.

Frequently Asked Questions

Q1: Why did left atrial appendage closure fail to show noninferiority in the CLOSURE-AF trial?

The trial enrolled an exceptionally high-risk cohort with elevated baseline stroke and bleeding risks. Consequently, periprocedural complications and post-procedural antithrombotic requirements likely compromised the overall efficacy of the mechanical device compared to modern medical therapy.

Q2: How does the CLOSURE-AF trial impact daily clinical practice?

Clinicians should not view mechanical closure as a universal substitute for anticoagulation. Instead, we must prioritize individualized shared decision-making, reserving device closure for patients with definitive contraindications to medical therapy.

References

1. Raco M et al. In AF at risk for stroke and bleeding, LAAC was not noninferior to medical therapy for a composite of thromboembolic and safety events. Ann Intern Med. 2026 Jul 07. doi: 10.7326/ANNALS-26-02439-JC. PMID: 42407076.
2. Landmesser U et al. Left Atrial Appendage Closure or Medical Therapy in Atrial Fibrillation. N Engl J Med. 2026 Apr 2;394(13):1270-1280. doi: 10.1056/NEJMoa2513310.