Arrhythmias & electrophysiologyMeta-analysis
Direct oral anticoagulants vs warfarin in Asian vs non-Asian patients with atrial fibrillation: a patient-level meta-analysis from COMBINE AF
- Patient-level meta-analysis of randomised trials (COMBINE AF), subgroup analysis by race
- pooled patient-level data from 4 pivotal RCTs
Authors' conclusion
Clinical outcomes with SD DOACs vs warfarin in patients with atrial fibrillation were generally even more favourable in patients of Asian than non-Asian race. Compared with warfarin, SD DOACs did not increase the risk of gastrointestinal bleeding in Asians.
Study context
- Population
- Patients with AF in the four pivotal RCTs of direct oral anticoagulants (DOACs) vs warfarin
- Comparison
- SD DOACs vs warfarin in Asians vs non-Asians
- Asiansn = 10,212
- Non-Asiansn = 61,471
Pooled result
As reported in the abstract
SD DOACs vs warfarin, by race
HR
- stroke/SEE, Asians
- .65 (95% CI .53-.80)
- stroke/SEE, non-Asians
- .86 (95% CI .78-.95)
- major bleeding, Asians
- .62 (95% CI .52-.75)
- major bleeding, non-Asians
- .91 (95% CI .84-.98)
- primary net clinical outcome (stroke/SEE, major bleeding or death), Asians
- .76 (95% CI .68-.85)
- primary net clinical outcome, non-Asians
- .94 (95% CI .90-.98)
Further pooled results
| Outcome | HR (CI) | |
|---|---|---|
| Lower-dose vs SD DOACs in Asians — Lower-dose DOACs vs SD DOACs · stroke/SEE | 1.57 (1.15–2.13) | |
| Lower-dose vs SD DOACs in Asians — Lower-dose DOACs vs SD DOACs | 1.23 (1.03–1.48) | |
| 0.512Hazard ratio (log scale) |
| Outcome | SD DOACs | Warfarin | Asians | Non-Asians | Estimate |
|---|---|---|---|---|---|
| Baseline: Asians vs non-Asians | mean 64.9 mL/min | mean 77.3 mL/min | |||
| Prior stroke/TIA | Not reported in the abstract | Not reported in the abstract | 37.2% | 26.6% | |
| Warfarin arm: median time in therapeutic range | Not reported in the abstract | Not reported in the abstract | median 57.7% | median 66.2% |
- Baseline: Asians vs non-Asians — Asians 3.2 years younger and 20 kg lighter; values are creatinine clearance
- P < .001 for each
- Warfarin arm: median time in therapeutic range — On warfarin, Asians had higher adjusted risk of stroke/SEE, major bleeding, intracranial haemorrhage, GI bleeding and primary net clinical outcome
- P < .001
- Lower-dose vs SD DOACs in Asians: secondary net clinical outcome (stroke/SEE, intracranial haemorrhage or death)
SD DOACs across body weight and creatinine clearance in Asians
- SD DOACs reduced clinical events across the wide range of body weight and creatinine clearance
Safety
| Outcome | HR (95% CI) | P value |
|---|---|---|
| Major bleeding — SD DOACs vs Warfarin · Asians · interaction P | .62 (.52-.75) | Pint < .02 |
| Major bleeding — SD DOACs vs Warfarin · non-Asians · interaction P | .91 (.84-.98) | Pint < .02 |
GI bleeding, standard-dose DOACs vs warfarin
- Asians: HR (95% CI)
- .92 [.69-1.23]
- Non-Asians: HR
- 1.41 [1.25-1.58] (95% CI)
- Increased GI bleeding only in non-Asians
- Pint = .009
- interaction P
Major bleeding, ICH, GI bleeding in the warfarin arm, Asians vs non-Asians
- Higher adjusted risk in Asians
Original publication
Direct oral anticoagulants vs warfarin in Asian vs non-Asian patients with atrial fibrillation: a patient-level meta-analysis from COMBINE AF. Eur Heart J. Published 30 April 2026. doi:10.1093/eurheartj/ehag246
Summarised from the published abstract; every number is checked against it