P4019The impact of age on the effectiveness and safety of the NOACs versus warfarin for stroke prevention in atrial fibrillation

Abstract

Background: Pivotal clinical trials have established non-vitamin K antagonist oral anticoagulants (NOACs) as viable alternatives to warfarin for stroke prevention in atrial fibrillation (AF) but age may be an important determinant of the risk/benefit of these therapies - indeed, RE-LY and ARISTOTLE demonstrated potential age interactions for certain endpoints. Purpose: To investigate the impact of age on the effectiveness and safety of dabigatran, rivaroxaban, and apixaban, comparing each agent to warfarin. Methods: We created three propensity-score matched cohorts of patients with nonvalvular AF: dabigatran versus warfarin (n=34,834), rivaroxaban versus warfarin (n=38,592), and apixaban versus warfarin (n=13,152). The primary effectiveness outcome was stroke or systemic embolism and the primary safety outcome was major bleeding. Cox proportional hazards models were used to compare each of the three agents to warfarin overall and by age category (18-64, 65-74 and ≥75 years) and we tested for a drug-age interaction. Results: Age interactions were noted for dabigatran and major bleeding and for rivaroxaban and stroke. Dabigatran was associated with lower risk of major bleed-ing among patients under 75 years, but trended toward higher risk in patients 75 years or older. Rivaroxaban was associated with higher risk of stroke in patients aged 18-64 years. Conclusions: Age appears to be an important determinant of the relative safety and effectiveness of the NOACs in comparison to warfarin (Table Presented).