Is Left Atrial Appendage Closure Safe for High-Risk AF?

Managing atrial fibrillation in patients with a high risk of stroke and bleeding presents a significant clinical challenge. Consequently, physicians often consider left atrial appendage closure as a viable alternative to long-term oral anticoagulation. However, a recent analysis of the landmark CLOSURE-AF trial has questioned this clinical practice. Specifically, researchers evaluated whether this device intervention could match physician-directed medical therapy in a highly vulnerable patient cohort.

Clinical Outcomes of Left Atrial Appendage Closure

The multicenter CLOSURE-AF trial enrolled 912 adult patients with non-valvular atrial fibrillation. Crucially, these participants faced high baseline risks, with a mean CHA2DS2-VASc score of 5.2. Additionally, their mean HAS-BLED score was 3.0, indicating extreme vulnerability. Investigators randomized the participants to either undergo left atrial appendage closure or receive physician-directed best medical care. Indeed, in the medical therapy arm, approximately 85% of eligible patients received direct oral anticoagulants. After a median follow-up of three years, the primary composite endpoint occurred in 155 patients in the device group. In contrast, only 127 patients in the medical therapy group experienced a primary endpoint event. Specifically, this equated to 16.83 events per 100 patient-years for the device group versus 13.27 events for the medical group. Therefore, the trial failed to demonstrate the non-inferiority of the device intervention. Furthermore, serious adverse events remained high in both groups, affecting over three-quarters of the participants.

Why the Intervention Did Not Meet Noninferiority

Several factors explain why this mechanical approach did not outperform standard pharmaceutical management. First, the trial focused on an exceptionally sick and vulnerable demographic. Consequently, procedural complications combined with existing comorbidities may have diluted the potential benefits of the device. Second, contemporary medical therapy, particularly direct oral anticoagulants, provides excellent protection with a manageable safety profile. Thus, physicians must not assume that mechanical closure is always superior to medication. Instead, clinicians should carefully evaluate individual patient factors before recommending invasive procedures. Ultimately, this study highlights the need for shared decision-making in cardiology, especially for patients with complex clinical profiles.

Frequently Asked Questions

Q1: Why did left atrial appendage closure fail to show noninferiority in this trial?

The device did not meet noninferiority because the trial enrolled highly vulnerable patients with severe comorbidities. Additionally, contemporary direct oral anticoagulants perform exceptionally well, raising the bar for mechanical interventions.

Q2: Who was enrolled in the CLOSURE-AF trial?

The trial enrolled 912 adult patients with atrial fibrillation who had a very high risk of both stroke and bleeding. Specifically, their mean CHA2DS2-VASc score was 5.2 and their mean HAS-BLED score was 3.0.

Q3: Should physicians stop recommending left atrial appendage closure?

No, physicians should not stop using the procedure entirely. Instead, they should decide on a case-by-case basis through shared decision-making rather than assuming the device is always safer.

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. Left Atrial Appendage CLOSURE in Patients with Atrial Fibrillation at High Risk of Stroke and Bleeding Compared to Medical Therapy (CLOSURE-AF). American College of Cardiology. March 2026.
3. Left Atrial Appendage Closure Not Noninferior to Medical Therapy in High-Risk Atrial Fibrillation. Straight Healthcare. March 2026.