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

Konstantin A Krychtiuk; Renato D Lopes; Daniel M Wojdyla; Shaun G Goodman; Ronald Aronson; Stephan Windecker; Roxana Mehran; Christopher B Granger; John H Alexander; Karen P Alexander

doi:10.1016/j.jacadv.2024.101335

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

JACC Adv. 2024 Oct 17;3(11):101335. doi: 10.1016/j.jacadv.2024.101335. eCollection 2024 Nov.

Authors

Konstantin A Krychtiuk¹, Renato D Lopes^{1

2}, Daniel M Wojdyla¹, Shaun G Goodman^{3

4}, Ronald Aronson⁵, Stephan Windecker⁶, Roxana Mehran⁷, Christopher B Granger^{1

2}, John H Alexander^{1

2}, Karen P Alexander^{1

2}

Affiliations

¹ Duke Clinical Research Institute, Durham, North Carolina, USA.
² Division of Cardiology, Duke Health, Durham, North Carolina, USA.
³ Canadian VIGOUR Centre, University of Alberta, Edmonton, Canada.
⁴ Terrence Donnelly Heart Centre, St Michael's Hospital, University of Toronto, Ontario, Canada.
⁵ Bristol-Myers Squibb, Lawrenceville, New Jersey, USA.
⁶ Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
⁷ Zena and Michael A. Weiner Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, and Cardiovascular Research Foundation, New York, New York, USA.

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.

Keywords: PCI; anticoagulation; apixaban; aspirin; atrial fibrillation; bleeding; multimorbidity.