Antithrombotic Strategies in Atrial Fibrillation After ACS and/or PCI: A 4-Way Comparison From AUGUSTUS

J Am Coll Cardiol. 2024 Sep 3;84(10):875-885. doi: 10.1016/j.jacc.2024.06.022.

Abstract

Background: The optimal antithrombotic regimen for patients with atrial fibrillation (AF) who had an acute coronary syndrome (ACS) or have undergone percutaneous coronary intervention (PCI) is not known.

Objectives: The authors sought to determine which antithrombotic regimen best balances safety and efficacy.

Methods: AUGUSTUS, a multicenter 2 × 2 factorial design randomized trial compared apixaban with vitamin K antagonist (VKA) and aspirin with placebo in patients with AF with recent ACS and/or PCI treated with a P2Y12 inhibitor. We conducted a 4-way analysis comparing safety and efficacy outcomes in the 4 randomized groups. The primary outcome was a composite of all-cause death, major or clinically relevant nonmajor bleeding, or hospitalization for cardiovascular causes over 6-month follow-up. Secondary outcomes included individual components of the primary endpoint.

Results: A total of 4,614 patients were enrolled. All patients were treated with a P2Y12 inhibitor. The primary endpoint occurred in 21.9% of patients randomized to apixaban plus placebo, 27.3% randomized to apixaban plus aspirin, 28.0% randomized to VKA plus placebo, and 33.3% randomized to VKA plus aspirin. Rates of major or clinically relevant nonmajor bleeding and hospitalization for cardiovascular causes were lower with apixaban and placebo compared with the other 3 antithrombotic strategies. There was no difference between the 4 randomized groups with respect to all-cause death.

Conclusions: In patients with AF and a recent ACS and/or PCI, an antithrombotic regimen that included a P2Y12 inhibitor and apixaban without aspirin resulted in a lower incidence of the composite of death, bleeding, or cardiovascular hospitalization than regimens including VKA, aspirin, or both. (An Open-label, 2 x 2 Factorial, Randomized Controlled, Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Aspirin Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome or Percutaneous Coronary Intervention; NCT02415400).

Keywords: acute coronary syndrome; antithrombotic regimen; atrial fibrillation; percutaneous coronary intervention.

Publication types

  • Randomized Controlled Trial
  • Multicenter Study
  • Comparative Study

MeSH terms

  • Acute Coronary Syndrome* / complications
  • Acute Coronary Syndrome* / drug therapy
  • Aged
  • Aspirin* / therapeutic use
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Factor Xa Inhibitors / therapeutic use
  • Female
  • Fibrinolytic Agents* / therapeutic use
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / methods
  • Pyrazoles* / therapeutic use
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Pyridones* / therapeutic use
  • Treatment Outcome
  • Vitamin K / antagonists & inhibitors

Substances

  • apixaban
  • Aspirin
  • Pyrazoles
  • Pyridones
  • Fibrinolytic Agents
  • Vitamin K
  • Factor Xa Inhibitors

Associated data

  • ClinicalTrials.gov/NCT02415400