AUGUSTUS

Clinical Trial Details

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

The purpose of this study is to examine, in a randomized controlled trial, the benefits and costs of the American Heart Association's (AHA) advisory for depression screen and treatment of post-acute coronary syndrome patients.

Key Findings

In patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or PCI and taking a P2Y12 inhibitor, there was less bleeding and hospitalizations with apixaban without aspirin. Ischemic events were differences were not significant for arms that included either or both vitamin K antagonist (VKA) and aspirin.

AUGUSTUS Trial Principal Investigator

Renato Lopes, MD, MHS, PhD, summarizes the results of the AUGUSTUS trial, which compared treatment outcomes for patients with AF and ACS and/or PCI, and also taking a P2Y12 inhibitor.

Purpose: Safety and efficacy of apixaban in patients with atrial fibrillation and a recent acute coronary syndrome or PCI.

Trial design: Phase 4. Open-label, 2 x 2 factorial, randomized, international (33 countries), controlled trial. Safety comparison for bleeding risk of apixaban (5 mg or 2.5 mg 2 times a day) ± aspirin vs. Vitamin K antagonist (VKA) (once daily) ± aspirin (81 mg acetylsalicylic acid film coated tablet once daily) vs. aspirin placebo. All patients were also on a P2Y12 inhibitor such as clopidogrel. Follow-up: 6 months. All medications are taken orally.

Primary endpoints: Rate of International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major (CRNM) bleeding during approximately 6 months of treatment with apixaban or VKA. Rate of major or CRNM during approximately 6 months of treatment with aspirin vs no aspirin.

Results: In patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or PCI and taking a P2Y12 inhibitor, there was less bleeding and hospitalizations with apixaban without aspirin. Ischemic events were differences were not significant for arms that included either or both vitamin K antagonist (VKA) and aspirin.

Swipe table left to see full data

AUGUSTUS Data
6-Month follow upApixabanVKAAspirinAspirin Placebo
Major/clinically relevant bleeding10.5%14.7%16.1%9.0%
HR 0.69, p>0.001
superiority and non-inferiority
HR 1.89 p>0.001
superiority
Death or hospitalization23.5%27.4%26.2%24.7
HR 0.83, p=0.002
for superiority
HR 1.08 p NS
for superiority
Death or ischemic event6.7%7.1%6.5%7.3%
HR 0.93, p NS
for superiority
HR 0.80 P NT
for superiority

Background

The AUGUSTUS trial studies apixaban safety in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous intervention. It examines the efficacy and safety of aspirin versus placebo and either non-vitamin K antagonist (VKA) (apixaban) or VKA oral antagonist (warfarin, for example) and a P2Y12 inhibitor like clopidogrel.

Trial design: Phase 4. Open-label, 2 x 2 factorial, randomized, international (33 countries), controlled trial. Safety comparison for bleeding risk of apixaban (5 mg or 2.5 mg 2 times a day) ± aspirin vs. Vitamin K antagonist (VKA) (once daily) ± aspirin (81 mg acetylsalicylic acid film coated tablet once daily) vs. aspirin placebo. All patients were also on a P2Y12 inhibitor such as clopidogrel. Follow-up: 6 months. All medications are taken orally.

Trial population: 4614 patients, ages 18-95 years, (median age 45 years), with atrial fibrillation and acute coronary syndrome or percutaneous coronary and stent placement in the past 14 days.

Primary endpoints:

  • Rate of International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major (CRNM) bleeding during approximately 6 months of treatment with apixaban or VKA.
  • Rate of major or CRNM during approximately 6 months of treatment with aspirin vs no aspirin.

Secondary endpoints:

  • Superiority of apixaban vs VKA for major + CRNM bleeding during 6 months of treatment.
  • Rate of composite death or ischemic events [stroke, MI, stent thrombosis, urgent revascularization] with apixaban vs VKA during 6 months of treatment.
  • Composite of death and ischemic events for aspirin vs placebo during 6 months of treatment.
  • All-cause death or rehospitalization with apixaban vs VKA during 6 months of treatment.
  • All-cause death or rehospitalization with aspirin or no aspirin during 6 months of treatment.

Results:

Primary endpoints: Risk of major or clinically relevant bleeding of apixaban ± aspirin vs vitamin K antagonist ± aspirin (all patients also on P2Y12 inhibitors such as clopidogrel).

  • Major or clinically relevant bleeding:
    • Apixaban 10.5%, VKA 14.7%, hazard ratio, 0.69, p<0.001 for non-inferiority and superiority
    • Aspirin 16.1%, aspirin placebo 9.0%, hazard ratio, 1.89, p<0.001 for superiority

Secondary endpoints:

  • Death or hospitalization
    • Apixaban 23.5%, VKA 27.4%, HR 0.83, p=0.002 for superiority
    • Aspirin 26.2%, VKA 24.7%, HR 1.08, p NS for superiority
       
  • Death or ischemic event
    • Apixaban 6.7%, VKA 7.1%, HR 0.93, p NS for superiority
    • Aspirin 6.5%, VKA 7.3%, HR 0.89, P NT for superiority

Key Words
Vitamin K, aspirin, apixaban, atrial fibrillation, non-steroidal anti-inflammatory drugs, myocardial infarction, percutaneous intervention, acute coronary syndrome

Related Clinical Topics
AF, drug discovery, Acute coronary syndrome, intervention

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