Effectiveness and Safety of Oral Anticoagulants Among Non-Valvular Atrial FibrillationPatients with Polypharmacy

Aims: Polypharmacy is prevalent among non-valvular atrial fibrillation (NVAF) patients and presents a potential issue for the effective management of NVAF. This study compared the risk of stroke/systemic embolism (SE) and major bleeding (MB) among NVAF patients with polypharmacy newly prescribed oral anticoagulants (OACs).

Methods and results: A retrospective study of NVAF patients with polypharmacy who initiated OACs from 01JAN2013-30SEP2015 was conducted using US CMS Medicare and four commercial databases. Polypharmacy was defined as ≥ 6 concomitant medications on the index date. Propensity score matching was conducted to compare non-Vitamin K antagonists OACs (NOACs) to warfarin as well as between NOACs. Cox proportional hazard models were used to evaluate the risk of stroke/SE and MB. A total of 188,893 patients with polypharmacy were included, with an average of 8 concomitant medications (IQR 6-9). Compared to warfarin, apixaban (HR: 0.59, 95% CI: 0.52-0.68) and rivaroxaban (HR: 0.75, 95% CI: 0.69-0.83) were associated with a lower risk of stroke/SE. Apixaban (HR: 0.57, 95% CI: 0.54-0.61) and dabigatran (HR: 0.76, 95% CI: 0.66-0.88) were associated with a decreased risk of MB compared with warfarin. Compared with dabigatran and rivaroxaban, apixaban was associated with a lower risk of stroke/SE and MB. Dabigatran was associated with lower risk of MB compared with rivaroxaban.

Conclusions: In this observational study of anticoagulated NVAF patients with polypharmacy, effectiveness and safety profiles are more favorable for NOACs vs warfarin. Our observations are hypothesis generating and may help inform future clinical trials regarding appropriate OAC treatment selection in polypharmacy patients.