Arrhythmias & electrophysiologyMeta-analysis
Heterogeneity of Treatment Effect of Direct Oral Anticoagulants (DOACs) vs Warfarin in Atrial Fibrillation
- Individual patient data from the COMBINE-AF data set pooling 4 pivotal randomized trials of DOACs vs vitamin K antagonists (VKAs) in atrial fibrillation (AF)
- model-based clustering
- Cox regression and gradient boosting analyses adapted for time-to-event data
Authors' conclusion
Renal function, age, and BMI are key determinants of anticoagulant treatment benefit in AF. In regions with limited access to DOACs, these findings suggest that some lower-risk patient profiles may derive similar outcomes with VKAs, although differences were not statistically significant.
Study context
- Population
- Patients with atrial fibrillation (AF) in randomized trials of DOACs vs VKAspatients included · warfarin 29,272 · standard dose DOACs 29,362
- Participants
- 58,634 patients
- Comparison
- DOACs vs VKAs
- standard dose DOACsn = 29,362
- warfarinn = 29,272reference
Pooled result
As reported in the abstract
NCO (composite of all-cause death, disabling or fatal stroke, and intracranial or fatal bleeding), high-risk cluster
Hazard ratio
0.86
95% CI 0.81–0.92
P < 0.001
standard dose DOACs vs warfarin
HR 0.86 (95% CI 0.81–0.92); P < 0.001
Further pooled results
| Outcome | HR (95% CI) | P value | |
|---|---|---|---|
| NCO, low-risk cluster · low-risk cluster | 0.93 (0.85–1.03) | P = 0.154 | |
| 0.512Hazard ratio (log scale) |
- NCO, low-risk cluster: p-interaction = 0.115
Patient subgroups identified by clustering
- high-risk cluster mean creatinine clearance
- 55.1 mL/min
- high-risk cluster age
- 75.6 years
- high-risk cluster BMI
- 26.6 kg/m²
- low-risk cluster mean creatinine clearance
- 101 mL/min
- low-risk cluster age
- 64.2 years
- low-risk cluster BMI
- 32.3 kg/m²
Predictors of treatment heterogeneity
- Primary predictors of treatment heterogeneity were renal function, age, and BMI
- no statistically significant treatment-by-subgroup interactions were identified
Original publication
Heterogeneity of Treatment Effect of DOACs vs Warfarin in Atrial Fibrillation. JACC Adv. doi:10.1016/j.jacadv.2026.102915
Summarised from the published abstract; every number is checked against it