Risk of Stroke and Bleeding in Atrial Fibrillation Treated with Apixaban Compared with Warfarin

A previous FDA study reported a favorable benefit risk for apixaban compared with warfarin for stroke prevention in older non-valvular atrial fibrillation (NVAF) patients (≥ 65 years). However, it remains unclear whether this favorable benefit risk persists in other populations including younger users. We examined if a similar benefit risk was observed in the Sentinel System and if it varied by age group.

To examine the risk of ischemic stroke, gastrointestinal (GI) bleeding, and intracranial hemorrhage (ICH) in apixaban users compared with warfarin users in Sentinel Distributed Database (SDD).

A retrospective new user cohort study was conducted among patients, 21 years and older initiating apixaban and warfarin for NVAF, between December 28, 2012, and June 30, 2018, in the SDD.

Cox proportional hazard regression was used to estimate the hazard ratios (HR) and 95% confidence intervals (95% CI) for each outcome (ischemic stroke, GI bleeding, and ICH) in propensity score matched apixaban users compared with the warfarin users. Subgroup analyses by age (21-64, 65-74, and 75+ years) were conducted.

After matching, 55.3% and 58.4% (n = 55,038) of the apixaban and warfarin users were included in the main analysis. GI bleeding was the most common outcome. The HR (95% CI) for GI bleeding, ICH, and ischemic stroke in apixaban users compared with warfarin users were 0.57 (0.50-0.66), 0.53 (0.40-0.70), and 0.56 (0.45-0.71) respectively. The reduced risk of these outcomes in apixaban compared with warfarin users persisted across age groups.

In NVAF patients of all ages initiating either apixaban or warfarin for stroke prevention in the Sentinel System, apixaban was associated with a decreased risk of GI bleeding, ICH, and ischemic stroke compared with warfarin. Among patients less than 65 years of age, apixaban use was associated with a decreased risk of GI bleeding and ischemic stroke.