Direct oral anticoagulants vs warfarin in Asian vs non-Asian patients with atrial fibrillation: a patient-level meta-analysis from COMBINE AF.

Summary

Across 71,683 participants in the pivotal AF trials, Asians on warfarin had higher adjusted risks than non-Asians, whereas standard-dose DOACs delivered larger relative reductions in stroke/SEE, major bleeding, and net outcomes in Asians. In Asians, standard-dose DOACs did not increase GI bleeding, and lower-dose DOACs worsened outcomes.

Key Findings

• Standard-dose DOACs vs warfarin: greater relative reduction in stroke/SEE in Asians (HR 0.65) than non-Asians (HR 0.86).
• Major bleeding reduced more in Asians with standard-dose DOACs (HR 0.62) versus non-Asians (HR 0.91).
• No GI bleeding increase with standard-dose DOACs in Asians (HR 0.92) but increase in non-Asians (HR 1.41).
• Lower-dose DOACs in Asians increased stroke/SEE risk (HR 1.57) versus standard dose.

Clinical Implications

Prefer standard-dose DOACs over warfarin or lower-dose DOACs in Asian patients with AF, with no excess GI bleeding and consistent benefits across body weight and renal function.

Limitations

• Post hoc subgroup analyses may be vulnerable to residual confounding despite randomized origins.
• Warfarin time-in-therapeutic-range differed by race, potentially mediating some effects.

Future Directions

Prospective trials or pragmatic registries in Asian populations to confirm optimal DOAC dosing and explore genotype-guided anticoagulation.