Adding catheter ablation to anticoagulation therapy did not significantly reduce recurrent stroke or other major cardiovascular outcomes among patients with atrial fibrillation and a recent ischemic stroke, according to a randomized clinical trial published in JAMA Neurology.

In the STABLED trial, researchers compared standard therapy with edoxaban alone vs edoxaban plus catheter ablation performed within 1 to 6 months after stroke onset. Standard therapy plus catheter ablation did not significantly reduce the risk of the primary composite outcome of recurrent ischemic stroke, systemic embolism, all-cause death, or hospitalization for heart failure.

Trial Design and Population

The open-label, parallel-group randomized clinical trial enrolled 251 patients at 45 centers in Japan between January 2018 and March 2021 and followed them through March 2024. Patients were aged 20 to 85 years with electrocardiogram-confirmed nonvalvular atrial fibrillation and an ischemic stroke within the previous 6 months. All participants received the factor Xa inhibitor edoxaban and had a modified Rankin Scale score of 3 or less.

Two patients withdrew consent, leaving 249 patients in the intention-to-treat population: 124 assigned to standard therapy and 125 assigned to catheter ablation plus standard therapy. Mean age was 71.7 years, and 75% were male. The mean CHADS₂ score was 3.3, indicating elevated baseline stroke risk.

Patients in the ablation group underwent pulmonary vein isolation–based catheter ablation after at least 4 weeks of edoxaban therapy. The median time between randomization and ablation was 65 days. Median follow-up exceeded 3 years.

Primary Outcome

During follow-up, the primary composite outcome occurred in 22 patients in each group. Event rates were 4.9 per 100 person-years in the standard-therapy group and 5.6 per 100 person-years in the ablation group, corresponding to a hazard ratio of 1.11.

Event rates for individual components were comparable between groups:

• Recurrent ischemic stroke: 3.1 vs 2.5 events per 100 person-years with standard therapy vs ablation

• Hospitalization for heart failure: 1.5 vs 1.0 events per 100 person-years

• All-cause death: 1.0 vs 2.8 events per 100 person-years

No systemic embolic events occurred in either group.

Secondary and Safety Outcomes

Secondary end points showed similar event counts between groups. Stroke occurred in 14 patients receiving standard therapy and 13 patients in the ablation group. Hemorrhagic stroke occurred only in the ablation group, affecting three patients.

Major bleeding occurred in three patients receiving standard therapy and eight patients in the ablation group, while intracranial hemorrhage occurred in two and four patients, respectively. Gastrointestinal bleeding occurred in 13 patients receiving standard therapy and 10 receiving ablation.

Procedure-related complications were uncommon. Two adverse events were associated with catheter ablation—one cardiac tamponade and one stroke—each affecting 0.8% of patients undergoing the procedure.

Approximately 14% of participants crossed over between treatment groups during the study, including 19 patients assigned to ablation who ultimately received standard therapy alone and 16 assigned to standard therapy who underwent ablation.

Interpretation and Limitations

Researchers noted that recurrent ischemic stroke occurred less frequently than expected in the anticoagulation-only group, which may reflect consistent use of direct oral anticoagulants and advances in atrial fibrillation management. The lower-than-anticipated event rate reduced the study’s statistical power to detect differences between groups.

Other limitations included treatment crossover, uncertainty about causes of death during the COVID-19 pandemic, and the study’s conduct exclusively in Japan, which may limit generalizability to other populations.

“[O]ur findings do not demonstrate a clear clinical benefit of catheter ablation in this patient population,” wrote lead author Kazumi Kimura, MD, PhD, of Nippon Medical School in Tokyo, Japan, and Kumamoto University Hospital, and colleagues.

Full disclosures can be found in the study.

Source: JAMA Neurology