Antithrombotic Therapy in Patients With Atrial Fibrillation After Acute Coronary Syndromes or Percutaneous Intervention

J Am Coll Cardiol. 2022 Feb 8;79(5):417-427. doi: 10.1016/j.jacc.2021.11.035.


Background: The use of apixaban instead of vitamin K antagonists (VKA) as well as dropping aspirin results in less bleeding and comparable ischemic events in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention treated with a P2Y12 inhibitor.

Objectives: The authors assessed the safety and efficacy of antithrombotic regimens according to HAS-BLED and CHA2DS2-VASc scores in AUGUSTUS (The Open-Label, 2 × 2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention).

Methods: In AUGUSTUS, 4,614 patients were randomized in a 2-by-2 factorial design to open-label apixaban or VKA and blinded aspirin or placebo. The primary endpoint was major or clinically relevant nonmajor bleeding over 6 months of follow-up. Cox proportional hazards models were used to assess treatment effects by baseline HAS-BLED (≤2 vs ≥3) and CHA2DS2-VASc (≤2 vs ≥3) scores.

Results: Of 4,386 (95.1%) patients with calculable scores, 66.8% had HAS-BLED ≥3 and 81.7% had CHA2DS2-VASc ≥3. Bleeding rates were lower with apixaban than VKA irrespective of baseline risk (HR: 0.57; 95% CI: 0.41-0.78 [HAS-BLED ≤2]; HR: 0.72; 95% CI: 0.59-0.88 [HAS-BLED ≥3]; interaction P = 0.23). Aspirin increased bleeding irrespective of baseline risk (HR: 1.86; 95% CI: 1.36-2.56 [HAS-BLED ≤2]; HR: 1.81; 95% CI: 1.47-2.23 [HAS-BLED ≥3]; interaction P = 0.88). Apixaban resulted in a lower risk of death or hospitalization than VKA without a significant interaction with baseline stroke risk (HR: 0.92; 95% CI: 0.67-1.25 [CHA2DS2-VASc ≤2]; HR: 0.82; 95% CI: 0.73-0.94 [CHA2DS2-VASc ≥3]; interaction P = 0.53).

Conclusions: Our findings support the use of apixaban and a P2Y12 inhibitor without aspirin for most patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention, irrespective of a patient's baseline bleeding and stroke risk (NCT02415400).

Keywords: antithrombotic therapy; apixaban; atrial fibrillation; bleeding; risk scores; stroke.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / therapy*
  • Aged
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / etiology
  • Dose-Response Relationship, Drug
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention / methods*
  • Treatment Outcome


  • Fibrinolytic Agents

Associated data