LAA Closure in the Setting of Atrial Fibrillation Ablation: Lessons From the OPTION Trial

When primary results of the landmark multicenter OPTION trial were reported in late 2024, they showed that left atrial appendage closure (LAAC) significantly reduced the risk of nonprocedural bleeding compared with oral anticoagulation (OAC) while maintaining similarly low rates of stroke, death or systemic embolism among patients at moderate to high stroke risk undergoing catheter ablation for atrial fibrillation (AF).

The study’s significance got it published in the New England Journal of Medicine, but insights from the trial do not end there. Principal investigator Oussama Wazni, MD, MBA, recently shared other notable lessons learned from OPTION — including data from new secondary analyses — in a late-breaking presentation at the 2025 annual meeting of the Heart Rhythm Society (HRS). These lessons include the following:

• Catheter ablation appears to lower stroke risk in and of itself.
• Bleeding was significantly reduced with LAAC versus OAC even after procedural bleeding was included in the safety analysis.
• Neither concomitant nor sequential LAAC compromises AF ablation rhythm outcomes or influences AF recurrence.

“We undertook OPTION to determine how best to approach stroke prevention following ablation for AF,” says Dr. Wazni, Section Head of Cardiac Electrophysiology and Pacing at Cleveland Clinic. “Current guidelines state that the decision whether or not to give anticoagulation after an ablation depends on the patient’s CHA₂DS₂-VASc score, not on the perceived outcome of the ablation. Yet continuing anticoagulation in higher-risk patients can make them more susceptible to bleeding. So we proposed studying whether closing the LAA, which is where most strokes originate in this population, could protect from stroke and also from bleeding since anticoagulation could be avoided.”

Recapping OPTION essentials

OPTION directly compared LAAC with OAC after AF ablation in 1,600 patients from 114 global sites, all of whom had an elevated CHA₂DS₂-VASc score (mean of 3.5), indicating moderate to high stroke risk. Patients were randomized 1:1 to undergo LAAC (using the Watchman FLX device) or to continue OAC following ablation. Notably, 95% of patients in the OAC arm received newer nonwarfarin direct oral anticoagulants, predominantly apixaban and rivaroxaban. The trial followed patients for 36 months.

The initial study report yielded the following key findings:

• The primary safety endpoint — nonprocedural major or clinically relevant nonmajor bleeding — occurred in 8.5% of the LAAC group versus 18.1% of the OAC group (P < .001 for superiority), largely driven by a difference in clinically relevant nonmajor bleeding.
• The primary efficacy endpoint — a composite of all-cause death, stroke or systemic embolism — was equivalent between the groups, occurring in 5.3% with LAAC and 5.8% with OAC (P < .001 for noninferiority).

Lessons learned from OPTION

Dr. Wazni’s presentation at the HRS meeting focused on deeper analysis of the OPTION data, yielding the additional insights recapped below.

1. Ablation’s potential role in stroke risk reduction. One of the study’s most intriguing findings was the low overall stroke rate. Whereas the study population’s mean CHA₂DS₂-VASc score of 3.5 would typically predict an annual stroke risk of 2% to 3% (even with anticoagulation), the observed stroke rates over three years were much lower: 1.2% in the LAAC arm and 1.3% in the OAC arm. “This is much lower than expected based on historical data,” Dr. Wazni says. “While OPTION was not designed to study the effect of ablation on stroke risk independently, these low observed rates suggest that ablation itself likely contributes to lowering the risk of stroke. I can now advise patients that ablation is likely to lower their stroke risk to some degree, in addition to treating their arrhythmia.”
2. Refined bleeding analysis including procedural events. While the initial primary safety endpoint excluded procedural bleeding, Dr. Wazni shared an additional bleeding analysis that included procedural bleeding events. This showed that even when accounting for bleeding risk associated with the device implant procedure, the bleeding rate in the LAAC arm increased only slightly, from 8.5% to 9.5%, and remained significantly lower than the 18.1% rate in the OAC arm. “This reinforces the substantial safety benefit of the LAAC strategy in terms of bleeding, even when considering any up-front procedural risk,” Dr. Wazni notes.
3. Effect on ablation efficacy. A potential concern with performing LAAC, especially when done concomitantly with ablation, is whether the presence of the device, or modifications to the ablation strategy to accommodate the device, might compromise the ablation success rate. Dr. Wazni presented a new secondary analysis specifically addressing this question. The analysis showed that rates of AF recurrence were statistically similar between the LAAC and OAC groups, and that the timing of LAAC relative to ablation — either concomitant or sequential — had no impact on AF recurrence. “Including the LAAC procedure does not decrease the success rate of ablation,” Dr. Wazni says. “This is a reassuring finding for clinicians considering a combined approach.”

Clinical implications and what’s next

“The findings from OPTION suggest a paradigm shift in managing stroke risk after AF ablation for eligible patients, as LAAC offers significant bleeding risk reduction relative to OAC while providing comparable stroke protection,” says Mohamed Kanj, MD, Co-Director of Electrophysiology Laboratories at Cleveland Clinic. “Additionally, the ability to avoid chronic OAC therapy is highly appealing to patients, as is the convenience of performing both ablation and LAAC during a single procedure.”

Performing AF ablation and LAAC together is something that Cleveland Clinic has significant experience with, having combined the procedures in more than 500 cases since 2017, primarily in patients who meet the current indication for LAAC — i.e., those at high bleeding risk who need stroke prevention but cannot tolerate OAC therapy. In fact, Dr. Wazni and Cleveland Clinic have led efforts to convince payers that performing these procedures together is clinically appropriate, cost-effective and in patients’ best interest. These efforts helped prompt the Centers for Medicare & Medicaid Services to establish a specific payment code for the combined procedure.

Despite these developments, Dr. Wazni notes that the current indication for LAAC with the Watchman device remains limited to patients who have reason to seek a nonpharmacologic alternative to chronic OAC, such as prior major bleeding or a high risk of bleeding. All patients enrolled in the OPTION trial differed from this indicated population in that they were eligible to take anticoagulation therapy. The OPTION trial sponsor is expected to pursue a new indication for the Watchman device in patients undergoing AF ablation regardless of bleeding risk.

Meanwhile, cost-effectiveness analyses using OPTION trial data are now underway, which will likely inform decisions around broader adoption and reimbursement of LAAC in the setting of AF ablation.

For further perspectives on LAAC and ablation from Drs. Wazni and Kanj, listen to the below episode of Cleveland Clinic's Cardiac Consult podcast for medical professionals.

The OPTION trial was funded by Boston Scientific, which markets the LAAC device used. Dr. Wazni reports that he has served as a consultant and speaker for Boston Scientific.