Effectiveness and safety of rivaroxaban vs. apixaban in patients with atrial fibrillation and peripheral artery disease

To assess whether rivaroxaban is associated with a decreased risk of major adverse limb events (MALE), stroke, systemic embolism (SE), and major bleeding (MB) among patients with non-valvular atrial fibrillation (NVAF) and peripheral artery disease (PAD), compared with apixaban.

We conducted a population-based cohort study using the UK Clinical Practice Research Datalink. Patients aged ≥45 years with incident NVAF and PAD who initiated rivaroxaban or apixaban between 2013 and 2021 were included. Primary effectiveness outcomes were MALE, and a composite of ischaemic stroke, transient ischaemic attack (TIA), or SE. The primary safety outcome was MB. The risk of major cardiovascular events (MACE) was assessed as a secondary outcome. Confounding was addressed using propensity score fine stratification and weighting. Weighted Cox proportional hazards models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). The cohort included 6170 new users of rivaroxaban and 9990 new users of apixaban (44% female; mean [SD] age 78.5 [9.2] years). Incidence rates were similar for MALE (6.7 vs. 5.6/1000 person-years; adjusted HR (aHR): 1.20; 95% CI 0.87–1.65), stroke/TIA/SE (24.5 vs. 21.3/1000 person-years; aHR: 1.15; 95% CI 0.97–1.36), and MACE (40.1 vs. 35.9 per 1000 person-years; aHR 1.10: 95% CI 0.94–1.28). Major bleeding rates were higher with rivaroxaban (46.1 vs. 29.8/1000 person-years; aHR: 1.55; 95% CI 1.36–1.77).

In patients with NVAF and PAD, rivaroxaban was associated with a similar risk of MALE and stroke/TIA/SE, but a higher risk of MB compared with apixaban. These findings support apixaban as a potentially safer anticoagulant in this high-risk population.