STABLED
(2026)Objective
To evaluate the efficacy and safety of catheter ablation added to standard edoxaban therapy for reducing recurrent stroke or composite outcomes in patients with nonvalvular atrial fibrillation and a recent ischemic stroke.
Study Summary
• The observed event rate was lower than anticipated, leaving the trial underpowered to detect a clinically meaningful difference.
• All-cause mortality was numerically higher in the ablation arm (2.8 vs 1.0 per 100 person-years), and major bleeding was more frequent with ablation, though neither difference was statistically significant.
Intervention
Catheter ablation (pulmonary vein isolation +/- additional atrial ablation) performed at least 4 weeks after edoxaban initiation and within 1-6 months of index stroke, added to standard edoxaban therapy
Inclusion Criteria
Age 20-85 years; nonvalvular atrial fibrillation confirmed on ECG; ischemic stroke within 6 months prior to enrollment; on or planned to start edoxaban; mRS score 3 or less
Study Design
Arms: Standard therapy (edoxaban) vs Standard therapy + catheter ablation
Patients per Arm: 124 (standard therapy), 125 (ablation)
Outcome
• Recurrent ischemic stroke: 3.1 vs 2.5 per 100 person-years (HR 0.75; 95% CI 0.33-1.70); all-cause death: 1.0 vs 2.8 per 100 person-years (HR 2.79; 95% CI 0.98-7.92; P=.05).
• Major bleeding: 0.6 vs 1.9 per 100 person-years (HR 2.99; 95% CI 0.79-11.3); ablation-related serious adverse events in 2 patients (cardiac tamponade and stroke, 0.8% each).
Bottom Line
In patients with nonvalvular AF and a recent ischemic stroke, catheter ablation added to edoxaban did not significantly reduce the primary composite endpoint of recurrent ischemic stroke, systemic embolism, all-cause death, or hospitalization for heart failure compared to edoxaban alone. The trial was likely underpowered due to lower-than-anticipated event rates.
Major Points
- Multicenter open-label RCT conducted at 45 sites in Japan; 249 patients randomized 1:1
- Median follow-up exceeded 3 years (3.7 years standard therapy, 3.5 years ablation)
- Primary composite endpoint occurred at identical rates per group (18.0% each) but with slightly higher per-person-year rate in ablation arm (5.6 vs 4.9 per 100 person-years; HR 1.11, P=.70)
- Recurrent ischemic stroke trended numerically lower with ablation (2.5 vs 3.1 per 100 person-years; HR 0.75) but did not reach significance
- All-cause mortality was numerically higher in the ablation arm (2.8 vs 1.0 per 100 person-years; HR 2.79; P=.05), though confidence intervals crossed 1.0
- Hospitalization for heart failure was numerically lower with ablation (1.0 vs 1.5 per 100 person-years; HR 0.66) but not significant
- Major bleeding was more frequent in the ablation arm (1.9 vs 0.6 per 100 person-years; HR 2.99), also not significant
- Two ablation-related serious adverse events: 1 cardiac tamponade and 1 stroke (0.8% each)
- Crossover rate was 14% overall (15.2% ablation-to-control; 12.9% control-to-ablation)
- Study was underpowered: assumed 15% annual event rate in control arm, actual rate was approximately 4.9 per 100 person-years
- Conducted exclusively in Japan; generalizability to other ethnic populations uncertain
Study Design
- Study Type
- Multicenter open-label parallel-group randomized clinical trial
- Randomization
- Yes
- Blinding
- Open-label; no blinding of investigators or participants. Randomization stratified by CHADS2 score (<4 vs >=4) and AF type (paroxysmal vs other) via web-based allocation system (EPS Corporation).
- Sample Size
- 249
- Follow-up
- Minimum 3 years from final patient randomization; maximum approximately 6 years; median 3.7 years (standard therapy) and 3.5 years (ablation)
- Centers
- 45
- Countries
- Japan
Primary Outcome
Definition: Composite of recurrent ischemic stroke, systemic embolism, all-cause death, and hospitalization for heart failure (time to first event)
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 22 events (18.0%); 4.9 per 100 person-years | 22 events (18.0%); 5.6 per 100 person-years | 1.11 (0.62-2.01) | .70 |
Limitations & Criticisms
- Open-label design introduces potential performance and detection bias
- Severely underpowered: actual control event rate (~4.9/100 person-years) was far lower than the assumed 15% annual rate used for power calculations, leaving the trial unable to detect clinically meaningful differences
- Crossover rate of 14% dilutes treatment effect estimates in ITT analysis, consistent with the CABANA trial paradox
- Pre-procedure events in the ablation arm (2 patients experienced primary endpoint before ablation) may have inflated apparent harm in the ablation group
- Trial conducted exclusively in Japan (all-Japanese population), limiting generalizability to other ethnic groups
- COVID-19 pandemic-related visitation/operational restrictions may have limited cause-of-death ascertainment
- Ablation group had higher baseline antiplatelet use (14.4% vs 4.0%) and more frequent heart disease history (19.2% vs 14.5%), potentially confounding mortality and bleeding outcomes
- Higher CHA2DS2-VASc scores in ablation arm may reflect selection or stratification imbalance
- Sample size (249) was small for a complex cardiovascular endpoint trial with median 3+ year follow-up
- Edoxaban was the sole anticoagulant; results may not generalize to other DOACs
- No sham procedure control; open-label ablation may influence concomitant medication use and follow-up intensity
Citation
Kimura K et al. Catheter Ablation and Oral Anticoagulation for Secondary Stroke Prevention in Atrial Fibrillation: The STABLED Randomized Clinical Trial. JAMA Neurol. Published online March 2, 2026. doi:10.1001/jamaneurol.2026.0155