Outcomes of apixaban versus rivaroxaban in patients with nonvalvular atrial fibrillation

Background: Atrial fibrillation (AFib) is the most common cardiac arrhythmia amongst older patients, often resulting in stroke. Direct oral anticoagulants (DOACs), including apixaban and rivaroxaban, are commonly prescribed to reduce this risk. However, their comparative effectiveness is debated. This retrospective study aims to compare all-cause mortality, stroke, myocardial infarction (MI), embolic events, and bleeding outcomes in AFib/atrial flutter (AFlutter) patients treated with these two DOACs. Methods: This retrospective, cross-sectional study utilized data from the United States Collaborative Network of 64 academic medical centers/healthcare organizations, with approximately 116 million patients in the TriNetX database between 2013 and 2021. Patients included were aged ≥60 years, had a diagnosis of AFib and/or AFlutter, and started treatment with apixaban or rivaroxaban within three months of diagnosis. Exclusions included pre-existing outcomes (stroke/MI), prosthetic heart valves, mitral valve disease, or concurrent use of other anticoagulants. Groups were propensity matched for demographics, eight preexisting diseases associated with mortality, other valvular heart disease, and the use of heparin or enoxaparin. Outcomes evaluated over a 3-year period included all-cause mortality, stroke, MI, peripheral emboli, intracranial hemorrhage (ICH), blood transfusions, and gastrointestinal (GI) bleeds. Results: A cohort of 241,082 AFib and/or AFlutter patients were identified (apixaban: n=157,888 and rivaroxaban: n=67,087). The apixaban and rivaroxaban cohorts had mean ages of 72.7 and 71.5 years, with male-to-female ratios of 1.3 and 1.5, respectively. After propensity score matching the sample consisted of 134,174 AFib and/or AFlutter patients (apixaban: n=67,087 and rivaroxaban: n=67,087). Prior to propensity score matching, rivaroxaban was associated with significantly lower rates of all outcomes except for ICH. After matching, patients prescribed rivaroxaban were associated with lower rates of all-cause mortality [relative risk (RR) =1.05; 95% confidence interval (CI): 1.02–1.09; P=0.002], 3-year stroke (RR =1.31; 95% CI: 1.22–1.42; P<0.001), MI (RR =1.30; 95% CI: 1.21–1.40; P<0.001), and peripheral emboli (RR =1.29; 95% CI: 1.03–1.62; P=0.03), but no significant difference in bleeding events (RR =1.09; 95% CI: 0.98–1.21; P=0.10), ICH (RR =1.02; 95% CI: 0.84–1.23; P=0.88), or GI bleeds (RR =1.04; 95% CI: 0.96–1.12; P=0.33). Conclusions: Rivaroxaban was associated with significantly lower rates of all-cause mortality, stroke, MI, emboli, blood transfusions, and GI bleeds compared to apixaban in the treatment of nonvalvular AFib and/or AFlutter before propensity score matching. After propensity score matching, significant differences persisted in the rates of stroke and MI favoring the rivaroxaban cohort. Based on these findings, rivaroxaban may be considered the preferred DOAC compared to apixaban for patients with nonvalvular AFib and/or AFlutter. The retrospective design limits causal inference, and reliance on electronic records may introduce misclassification; future studies should prioritize randomized prospective trials.