Antithrombotic Strategies According to Age: Insights from the AUGUSTUS Trial

Am J Med. 2024 Oct;137(10):958-965. doi: 10.1016/j.amjmed.2024.06.001. Epub 2024 Jun 13.

Abstract

Objective: We aimed to evaluate the safety and efficacy of antithrombotic strategies by age in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention in AUGUSTUS.

Methods: Patients were stratified into 3 age groups: <65, 65-74, and ≥75 years. Outcomes of interest were major or clinically relevant non-major bleeding, major bleeding, death or rehospitalization, and ischemic events. Treatment effects of apixaban vs. vitamin K antagonist (VKA) and aspirin vs. placebo were assessed across age groups using Cox models.

Results: Of 4614 patients, 1267 (27.5%) were <65, 1802 (39.0%) were 65-74, and 1545 (33.5%) were ≥75 years. Apixaban was associated with lower rates of major or clinically relevant non-major bleeding than VKA (<65: HR 0.69 [0.47-1.00]; 65-74: HR 0.57 [0.43-0.75]; ≥75: HR 0.81 [0.63-1.04]). Death or hospitalization occurred less often with apixaban, regardless of age. No differences were observed in rates of ischemic events between apixaban and VKA according to age. Aspirin was associated with higher rates of bleeding than placebo (<65: HR 1.67 [1.15-2.43]; 65-74: HR 2.32 [1.73-3.10]; ≥75: HR 1.69 [1.31-2.19]). Rates of death or rehospitalization and ischemic events were similar among patients receiving aspirin or placebo across age groups.

Conclusions: Apixaban was associated with greater absolute reduction in bleeding than VKA in older age groups, reflecting their higher hemorrhagic risk. Aspirin increased bleeding in all age groups vs. placebo. Our findings support the use of apixaban plus a purinergic receptor P2Y12(P2Y12) inhibitor without aspirin in patients with atrial fibrillation and recent acute coronary syndrome/percutaneous coronary intervention, regardless of age.

Keywords: Acute coronary syndrome; Age; Antithrombotic strategies; Apixaban; Aspirin; Atrial fibrillation; Percutaneous coronary intervention; Vitamin K antagonist.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Acute Coronary Syndrome* / drug therapy
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Aspirin* / adverse effects
  • Aspirin* / therapeutic use
  • Atrial Fibrillation* / complications
  • Atrial Fibrillation* / drug therapy
  • Factor Xa Inhibitors / adverse effects
  • Factor Xa Inhibitors / therapeutic use
  • Female
  • Fibrinolytic Agents* / adverse effects
  • Fibrinolytic Agents* / therapeutic use
  • Hemorrhage* / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention*
  • Pyrazoles* / adverse effects
  • Pyrazoles* / therapeutic use
  • Pyridones* / adverse effects
  • Pyridones* / therapeutic use
  • Vitamin K / antagonists & inhibitors

Substances

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