Limited real-world evidence exists on comparative effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus warfarin by NOAC dosage.

This subgroup analysis of the ARISTOPHANES (Anticoagulants for Reduction In STroke: Observational Pooled analysis on Health outcomes ANd Experience of patientS) study aimed to compare stroke/systemic embolism (S/SE), major bleeding (MB), and their respective components among non-valvular atrial fibrillation (NVAF) patients prescribed NOACs or warfarin, stratified by index NOAC dosage.

A retrospective observational study of NVAF patients initiating apixaban, dabigatran, rivaroxaban, or warfarin from 01JAN2013-30SEP2015 was conducted using CMS Medicare data and four US commercial claims databases, covering >180 million beneficiaries annually. Patient records were pooled after propensity score matching in each database between standard NOAC doses and warfarin (5mg BID apixaban-warfarin, 150mg BID dabigatran-warfarin, and 20mg QD rivaroxaban-warfarin), as well as lower NOAC doses and warfarin (2.5mg BID apixaban-warfarin, 75mg BID dabigatran-warfarin, and 10 or 15mg QD rivaroxaban-warfarin). Cox models were used to estimate S/SE and MB hazard ratios. 

In this study, only apixaban was associated with lower rates of S/SE and MB for both doses compared to warfarin. Future studies of patients who were appropriately dosed are warranted.