Underdosing apixaban ups risk of all-cause mortality

Underdosing of direct oral anticoagulants (DOACs) does not reduce the risk of bleeding, systemic embolization, or all-cause mortality in patients with atrial fibrillation (AF), reveals a study. In particular, inappropriate underdosing with apixaban results in increased all-cause mortality.

The authors analysed patients with AF who had a clinical indication for stroke prophylaxis (with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischaemic attack, vascular disease, age 65 to 74 years, sex category [CHA₂DS₂-VASc] of 2 or greater) and were prescribed one of the four clinically approved DOACs (apixaban, rivaroxaban, dabigatran, or edoxaban).

All-cause mortality, composite of stroke and systemic embolism, composite of myocardial infarction (MI), acute coronary syndromes (ACS), and coronary revascularization, and major bleeding were compared between patients appropriately dosed and those inappropriately underdosed.

A total of 8,125 patients were included and followed for a mean of 2.2 years, of whom 1,724 (21.2 percent) were inappropriately dosed.

After adjusting for baseline variable, no difference was observed in all-cause mortality, risk of stroke or systemic embolism, International Society on Thrombosis and Haemostasis (ISTH) major bleeding, or composite of myocardial infarction, acute coronary syndromes, or coronary revascularization between appropriately dosed and inappropriately underdosed patients.

Subgroup analysis revealed that only apixaban exhibited a heightened incidence of all-cause mortality (hazard ratio, 1.24, 95 percent confidence interval, 1.03–1.49) with inappropriate underdosing. No difference was noted in the remaining clinical outcomes.