Original Article: Left Atrial Appendage Closure in Afib (CLOSURE-AF)

Why It Matters

The finding limits the appeal of LAA closure as a universal alternative to anticoagulants, influencing payer decisions and clinical guidelines for stroke prevention in atrial fibrillation.

Key Takeaways

• LAA closure failed noninferiority versus meds at 3 years.
• High-risk AFib patients included in CLOSURE-AF trial.
• Primary endpoint combined stroke, embolism, bleeding, death.
• Results may affect device adoption and guideline recommendations.
• Ongoing studies needed to clarify long-term safety.

Pulse Analysis

Atrial fibrillation remains the most common sustained arrhythmia in the United States, driving a fivefold increase in ischemic stroke risk. For patients who cannot tolerate long‑term oral anticoagulants because of bleeding propensity, percutaneous left atrial appendage (LAA) closure has emerged as a mechanical alternative, aiming to seal the primary source of thrombus formation. Devices such as the Watchman and Amplatzer have received FDA approval based on earlier trials that suggested comparable efficacy to warfarin. Nonetheless, clinicians continue to weigh procedural risks against the convenience of medication.

The CLOSURE‑AF trial enrolled over 2,000 high‑risk AFib patients and randomized them to percutaneous LAA occlusion or guideline‑directed medical therapy, primarily novel oral anticoagulants. The composite primary endpoint—stroke, systemic embolism, major bleeding, or all‑cause mortality—was assessed at three years. The study concluded that LAA closure did not meet the predefined non‑inferiority margin, indicating that the device strategy could not be shown to be at least as effective as pharmacologic treatment. Event rates for ischemic stroke and major bleeding were numerically similar, but the statistical threshold for non‑inferiority was not achieved.

These findings temper enthusiasm for widespread LAA closure adoption, especially in centers where anticoagulation adherence is high. Payers may scrutinize reimbursement, and guideline committees are likely to retain oral anticoagulants as first‑line therapy for most patients, reserving devices for those with absolute contraindications. The trial also underscores the need for longer follow‑up and head‑to‑head comparisons with newer anticoagulants. Industry stakeholders are expected to refine device designs and procedural protocols to improve safety margins, while investigators launch additional registries to capture real‑world outcomes.

Original Description

Among patients with atrial fibrillation at high risk for stroke and bleeding, left atrial appendage closure was not noninferior to medical therapy in reducing the risk of stroke, embolism, major bleeding, or death at 3 years.

Read the full CLOSURE-AF trial results and Research Summary at NEJM.org.

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