PDF: ALONE-AF
(2025)Objective
To evaluate whether discontinuing oral anticoagulant therapy provides superior clinical outcomes compared with continuing oral anticoagulant therapy in patients without atrial arrhythmia recurrence for 1-year after AFib ablation
Study Summary
Intervention
Discontinuation of oral anticoagulant therapy vs continuation of direct oral anticoagulant therapy (apixaban or rivaroxaban)
Inclusion Criteria
Adults aged 19-80 years with history of AF who underwent catheter ablation, CHA2DS2-VASc score ≥1 for men or ≥2 for women, and no documented atrial arrhythmia recurrence for ≥1 year after ablation
Study Design
Arms: Discontinue oral anticoagulant therapy vs Continue oral anticoagulant therapy
Patients per Arm: 417 (discontinue) vs 423 (continue)
Outcome
• Major bleeding: 0% vs 1.4%
• Ischemic stroke: 0.3% vs 0.8%
Bottom Line
Among patients without documented atrial arrhythmia recurrence after catheter ablation for AF, discontinuing oral anticoagulant therapy resulted in a lower risk for the composite outcome of stroke, systemic embolism, and major bleeding compared with continuing direct oral anticoagulant therapy, primarily driven by reduced major bleeding events.
Major Points
- Multicenter randomized clinical trial of 840 patients across 18 hospitals in South Korea
- Patients had no AF recurrence for ≥1 year post-ablation and CHA2DS2-VASc score ≥1 (men) or ≥2 (women)
- Primary outcome (stroke, systemic embolism, major bleeding) occurred in 0.3% vs 2.2% at 2 years (p=0.02)
- Major bleeding drove the difference: 0% vs 1.4% in discontinue vs continue groups
- Ischemic stroke rates remained low: 0.3% vs 0.8% between groups
- NNT of 53 patients to prevent one primary outcome event at 2 years
- AF recurrence similar in both groups: 9.6% vs 8.7%
- Open-label design but outcomes adjudicated by blinded committee
Study Design
- Study Type
- Investigator-initiated, open-label, multicenter, superiority randomized clinical trial
- Randomization
- Yes
- Blinding
- Open-label design with blinded independent clinical event adjudication committee for outcome assessment
- Sample Size
- 840
- Follow-up
- 2 years
- Centers
- 18
- Countries
- South Korea
Primary Outcome
Definition: First occurrence of a composite of stroke, systemic embolism, and major bleeding at 2 years
| Control | Intervention | HR/OR | P-value |
|---|---|---|---|
| 8 patients (2.2%) | 1 patient (0.3%) | - (-3.5 to -0.3 percentage points) | 0.02 |
Limitations & Criticisms
- Open-label design carries inherent risk of reporting and ascertainment bias, though mitigated by blinded adjudication committee
- Overall number of events lower than anticipated, limiting statistical power
- Proportion of patients at high stroke risk may have been relatively small to detect potential disadvantage of stopping anticoagulation
- Primary outcome composite of stroke, systemic embolism, and major bleeding may bias results in favor of discontinuation given higher frequency of bleeding compared to ischemic events
- Study population predominantly East Asian with relatively few women (24.9%), limiting generalizability to other populations
- Monitoring strategy (1-3 day Holter every 6 months) may underestimate AF recurrence rates compared to continuous or longer-term monitoring
- No upper time limit on period from ablation to randomization
- Secondary outcome analyses not adjusted for multiple comparisons and should be regarded as exploratory
- Complete case analysis performed without imputation due to minimal missing data (0.2%)
Citation
JAMA. 2025;334(14):1246-1254