Medication adherence and antithrombotic therapy outcomes: insights from a post-hoc analysis of the AFIRE trial

Abstract Background The AFIRE (Atrial Fibrillation and Ischemic Events With Rivaroxaban in Patients With Stable Coronary Artery Disease) trial established noninferiority in efficacy and superiority in safety endpoints of rivaroxaban monotherapy over rivaroxaban plus antiplatelet therapy (combination therapy) in patients with atrial fibrillation (AF) and stable coronary artery disease (CAD). However, the impact of medication adherence to rivaroxaban on AFIRE study outcomes remains unclear. Purpose This post-hoc analysis aimed to explore the influence of medication adherence on AFIRE trial results. Methods Among 2,120 patients, participants were classified into adherent and non-adherent groups based on self-reported measures, which were further verified through on-site visits to the facilities. Adherent patients were defined as those who reported consistently taking their medication as prescribed. The primary efficacy endpoint comprised stroke, systemic embolism, myocardial infarction, unstable angina requiring revascularization, or all-cause death, including cerebral events. Analysis also examined differences in the primary efficacy endpoint between adherent and non-adherent patients. Results Of the 2,120 patients, 2,012 (94.9%) were adherent to rivaroxaban, while 108 (5.1%) were non-adherent. Among adherent patients, rivaroxaban monotherapy showed significantly better efficacy outcomes compared to combination therapy (hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.54–0.98; p=0.04, Figure 1A). However, primary efficacy outcomes did not significantly differ among non-adherent patients (HR 0.64, 95% CI 0.23–1.81, p=0.40, Figure 1B). Adherent patients exhibited improved outcomes relative to non-adherent patients, though this difference was not statistically significant (HR 1.68; 95% CI 0.99–2.85; p=0.05, Figure 2A). In clinically high-risk patients with a history of angina pectoris, those who demonstrated adherence to medication (n=1281) exhibited significantly better efficacy outcomes compared to non-adherent patients (n=68) (HR 1.97; 95% CI 1.09–3.56; p=0.03, Figure 2B). Conclusions Rivaroxaban monotherapy versus combination therapy showed favorable efficacy outcomes in patients with good adherence, consistent with the overall AFIRE trial. However, these benefits were not observed in non-adherent patients. Adherence to rivaroxaban is crucial for achieving its maximum therapeutic effect as monotherapy.Figure1Figure2