Apixaban and Limiting Aspirin for Patients With Atrial Fibrillation, Percutaneous Coronary Intervention, and Multimorbidity.

Abstract

Background Patients with atrial fibrillation (AF) after an acute coronary syndrome (ACS) and/or undergoing percutaneous coronary intervention (PCI) with multiple comorbidities are at increased risk for bleeding and ischemic events.Objectives This post-hoc analysis of AUGUSTUS describes the safety and efficacy of antithrombotic regimens in patients with multimorbidity.Methods AUGUSTUS was a 2 × 2 factorial, randomized controlled trial evaluating the safety of apixaban vs vitamin K antagonists (VKA) (open-label) and aspirin vs placebo (double-blind) in patients with AF and ACS and/or PCI treated with a P2Y12 inhibitor. Patients were categorized as having no multimorbidity (0-2 comorbidities), moderate multimorbidity (3-4 comorbidities), or high multimorbidity (≥5 comorbidities). The associations between multimorbidity and clinical outcomes and interactions with antithrombotic regimens were tested.Results Of 4,493 patients (97.4%) with available comorbidity data, 1,897 (42.2%) had no multimorbidity, 2,110 (47%) had moderate, and 486 (10.8%) had high multimorbidity. Patients with moderate (HR: 1.23; 95% CI: 1.02-1.47) and high (HR: 1.98; 95% CI: 1.55-2.54) multimorbidity had higher rates of International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant nonmajor (CRNM) bleeding compared to patients with no multimorbidity. No significant interaction between multimorbidity and apixaban vs vitamin K antagonists was observed for ISTH major bleeding/CRNM (P int = 0.415), death or hospitalization (P int = 0.092), or death or ischemic event (P int = 0.299). Similarly, no significant interaction between multimorbidity and aspirin vs placebo was seen for ISTH major bleeding/CRNM (P int = 0.261), death or hospitalization (P int = 0.646), or death or ischemic event (P int = 0.608).Conclusions Our findings support the standard use of apixaban plus a P2Y12 inhibitor in patients with AF and ACS/PCI, irrespective of the presence of multimorbidity.