Publications

Background: Warfarin is dependent on hepatic enzymes for metabolism while apixaban is a substrate for P-glycoprotein (P-gp) transport and hepatic CYP3A4 (3A4) metabolism. Medications that affect these pathways could modify the anticoagulant exposure and potentially their treatment effect.

Methods: Outcomes were compared between apixaban and warfarin using Cox proportional hazards modeling according to the use of interacting medications (IMs) at randomization in ARISTOTLE (n=18,201). IMs were identified as combined P-gp and 3A4 inhibitors or inducers and those highly probable for warfarin potentiation or inhibition.

Results: At randomization, 5547 (30.5%) patients were on an IM. Amiodarone (10.3%), diltiazem (7%), and verapamil (3.6%) were the most commonly used IMs. Patients on IMs were more likely to be female, taking aspirin and have a history of prior bleeding and were less likely to have had a prior stroke/TIA. Median TTR was 65.2% for those on vs. 66.3% not on an IM (P=0.015). No significant differences were observed on the treatment effect of apixaban vs. warfarin in patients on and off IMs for outcomes including stroke or SE (P interaction=0.79) or major bleeding (P interaction=0.75).

Conclusions: Use of interacting medications with OACs occurs often in patients with AF. Despite the potential for altered exposure, use of IMs was not associated with a significant change in the efficacy or safety of apixaban compared with warfarin in ARISTOTLE.