Standard-dose DOACs compared with warfarin reduced the primary net clinical outcome to a greater degree in Asian (HR 0.76; 95% CI 0.68-0.85) than non-Asian patients with atrial fibrillation.
Meta-Analysis (n=71,683)
Yes
Do DOACs improve clinical outcomes compared to warfarin in Asian versus non-Asian patients with atrial fibrillation?
Standard-dose DOACs provide greater relative reductions in stroke, systemic embolism, and major bleeding compared to warfarin in Asian patients than in non-Asian patients with atrial fibrillation.
Effect estimate: HR 0.76 (95% CI 0.68-0.85)
p-value: p=<0.02
BACKGROUND AND AIMS: Large-scale randomized data comparing clinical outcomes of atrial fibrillation patients of Asian vs non-Asian races are limited. METHODS: Data from A Collaboration Between Multiple Institutions to Better Investigate Non-Vitamin K Antagonist Oral Anticoagulant Use in Atrial Fibrillation, which pooled patient-level data from the four pivotal randomized trials of direct oral anticoagulants (DOACs) vs warfarin in patients with atrial fibrillation, were analysed. Baseline characteristics and clinical outcomes in patients of Asian race (Asians) vs non-Asian race were compared. The relative efficacy and safety of DOACs compared with warfarin in Asians vs non-Asians, assessing for interactions between race and treatment effect, were investigated. Outcomes across the range of body weight and creatinine clearance in Asians were also explored. RESULTS: A total of 10 212 Asian patients and 61 471 non-Asians were identified. Compared with non-Asians, Asians were on average 3.2 years younger and 20 kg lighter, had worse renal function (mean creatinine clearance 64.9 vs 77.3 mL/min), and had higher rates of prior stroke/transient ischaemic attack (37.2% vs 26.6%) (P < .001 for each). In the warfarin arm (median time in therapeutic range 57.7% for Asians vs 66.2% for non-Asians, P < .001), Asians had a higher adjusted risk of stroke/systemic embolic events (SEEs), major bleeding, intracranial haemorrhage, gastrointestinal bleeding, and primary net clinical outcome (stroke/SEE, major bleeding, or death). Compared with warfarin, standard-dose (SD) DOACs significantly reduced the risks in Asians to a greater degree than non-Asians for stroke/SEE (hazard ratio HR .65, 95% confidence interval .53-.80 vs HR .86, 95% confidence interval .78-.95), major bleeding (HR .62 .52-.75 vs HR .91 .84-.98), and primary net clinical outcome (HR .76 .68-.85 vs HR .94 .90-.98; Pint < .02 for each). Standard-dose DOACs increased gastrointestinal bleeding only in non-Asians (Asians HR .92 .69-1.23 vs non-Asians HR 1.41 1.25-1.58, Pint = .009). In Asians, SD DOACs reduced the risks of clinical events across the wide range of body weight and creatinine clearance. Compared with SD DOACs, lower-dose DOACs significantly increased the risk of stroke/SEE (HR 1.57 1.15-2.13) and secondary net clinical outcome (stroke/SEE, intracranial haemorrhage, or death; HR 1.23 1.03-1.48) in Asians. CONCLUSIONS: 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. Standard-dose DOACs are preferred over warfarin or lower-dose DOACs in patients of Asian race.
Chao et al. (2026) conducted a meta-analysis in Atrial fibrillation (n=71,683). Direct oral anticoagulants (DOACs) vs. Warfarin was evaluated on Primary net clinical outcome (stroke/systemic embolic events, major bleeding, or death) in Asian patients (HR 0.76, 95% CI 0.68-0.85, p=<0.02). Standard-dose DOACs compared with warfarin reduced the primary net clinical outcome to a greater degree in Asian (HR 0.76; 95% CI 0.68-0.85) than non-Asian patients with atrial fibrillation.