Anticoagulant dosing remains challenging in patients with heart failure (HF), nonvalvular atrial fibrillation (NVAF), and end-stage kidney disease (ESKD). A registry analysis published in Medicine evaluated long-term outcomes associated with off-label apixaban dosing in patients with HF, NVAF, and ESKD treated between 2018 and 2024.

The analysis included 480 patients receiving apixaban. Among them, 265 (55.2%) received an off-label reduced dose. Baseline thromboembolic and bleeding risk profiles, assessed using CHA₂DS₂-VASc and HAS-BLED scores, were similar across dosing groups. Outcomes included systemic thromboembolic events, bleeding complications, and all-cause mortality.

Findings 

• During a median follow-up of 48 months, no significant differences in systemic thromboembolic events were observed between patients receiving off-label underdoses, standard doses, or off-label overdoses (P=0.705).
• No significant differences in all-cause mortality were observed across dosing groups during follow-up.
• Bleeding risk did not differ significantly between the off-label underdose and standard-dose groups (P=0.600), the off-label overdose and standard-dose groups (P=0.395), or the underdose and overdose groups (P=0.469).
• In multivariable analysis, the CHA₂DS₂-VASc score independently predicted thromboembolic events (odds ratio, 1.818; 95% CI, 1.081-3.058; P=0.024).

The findings suggest that off-label apixaban dosing was not associated with higher risks of thromboembolic events, bleeding, or mortality in patients with HF, NVAF, and ESKD.