Asian patients with AF: standard-dose DOACs outperformed warfarin and reduced doses

Design

Individual patient-level meta-analysis of 4 randomised trials

Population

71,683 patients with AF (10,212 Asian)

Primary outcome

Stroke/systemic embolism, major bleeding, net clinical outcome

Effect

Asian stroke/SEE HR 0.65 (0.53–0.80); major bleeding HR 0.62; lower vs standard dose stroke HR 1.57

COMBINE AF, published in the European Heart Journal on 22 September, pooled individual patient data from the four pivotal trials of DOACs against warfarin in atrial fibrillation: 10,212 Asian and 61,471 non-Asian patients. Asian patients were about 20 kg lighter, had lower creatinine clearance (mean 64.9 vs 77.3 mL/min) and more prior stroke. On warfarin they spent less time in range (57.7% vs 66.2%) and had more strokes and bleeding.

Standard-dose DOACs reduced stroke or systemic embolism more in Asian patients (HR 0.65, 95% CI 0.53–0.80) than non-Asian (0.86), and reduced major bleeding more (0.62 vs 0.91). They did not increase gastrointestinal bleeding in Asian patients (HR 0.92), unlike in non-Asians (1.41). Benefits held across body weight and creatinine clearance. Compared with standard doses, lower doses increased stroke or embolism in Asian patients (HR 1.57, 1.15–2.13).

In Indian practice, DOACs are often under-dosed out of fear of bleeding, especially in lighter patients and those with CKD. These data argue against that: standard label doses, adjusted only by label criteria, gave the best results.

• Use standard-dose DOACs in Asian patients with AF unless label dose-reduction criteria are met
• Do not reduce doses because of ethnicity, lower weight alone or mild CKD
• Calculate creatinine clearance and review it regularly in CKD
• Prefer a DOAC over warfarin where cost allows; where warfarin is used, aim for good time in range

Why it matters

It directly challenges the widespread practice of under-dosing DOACs in Asian and kidney patients.

Don't overread it

Ethnicity was analysed as a subgroup of trials not designed to compare races, and few patients had severe CKD.

The statistics, in plain English

A hazard ratio of 0.65 means about a third fewer strokes than with warfarin. The interaction P values below 0.02 show the benefit genuinely differed between Asian and non-Asian patients, not just by chance. These are subgroup comparisons within randomised trials, so they are stronger than observational data but weaker than a dedicated trial.

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