ApoA-I Event Reducing in Ischemic Syndromes II - AEGIS-II

Apr 06, 2024
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Author/Summarized by Author:
Anthony A. Bavry, MD, MPH, FACC
Summary Reviewer:
Kim A. Eagle, MD, MACC
Trial Sponsor:
CSL Behring
Date Presented:
04/06/2024
Date Published:
04/06/2024
Original Posted Date:
04/06/2024
References

Contribution To Literature:

The AEGIS-II trial failed to show that CSL112 apoA-1 infusion reduces adverse CV outcomes after AMI.

Description:

The goal of the trial was to evaluate CSL112 apolipoprotein A-1 (apoA-1) infusion compared with placebo among patients with recent acute myocardial infarction (AMI). ApoA-1 increases cholesterol efflux capacity.

Study Design

  • Randomized
  • Parallel
  • Blinded
  • Placebo
  • Stratified

Patients with recent AMI were randomized to CSL112 apoA-1 infusion, 4 infusions of 6 g (n = 9,112) vs. placebo (n = 9,107). The goal of CSL112 apoA-1 infusion is to improve high-density lipoprotein cholesterol (HDL-C) function and cholesterol efflux capacity.

  • Total number of enrollees: 18,219
  • Duration of follow-up: 12 months
  • Mean patient age: 65.6 years
  • Percentage female: 25.9%
  • Percentage with diabetes: 68.7%

Inclusion criteria:

  • AMI within the last 5 days
  • ≥18 years of age
  • Multivessel coronary disease and 1) diabetes, or 2) ≥65 years of age, prior MI, or peripheral arterial disease

Exclusion criteria:

  • Hepatobiliary disease
  • Hemodynamic instability
  • Left ventricular ejection fraction <30%
  • Estimated glomerular filtration rate <30 cc/min/1.73 m2
  • Anticipated coronary artery bypass grafting
  • Weight <50 kg (<110 lbs)

Other salient features/characteristics:

  • Mean low-density lipoprotein cholesterol (LDL-C): 84 mg/dL
  • Mean HDL-C: 9 mg/dL

Principal Findings:

The primary outcome (cardiovascular [CV] death, MI, or stroke) at 90 days was 4.8% in the CSL112 apoA-1 infusion group vs. 5.2% in the placebo group (p = 0.24). The findings were similar among tested subgroups.

Secondary outcomes:

  • CV death, MI, or stroke at 365 days was 9.8% in the CSL112 apoA-1 infusion group vs. 10.5% in the placebo group (p = 0.14).
  • Among patients with LDL-C ≥100 mg/dL, CV death, MI, or stroke at 365 days was 7.8% in the CSL112 apoA-1 infusion group vs. 9.9% in the placebo group (p = 0.006, p for interaction = 0.07).

Interpretation:

Among patients with AMI and multivessel disease with additional CV risk factors, 4 weekly infusions of CSL112 apoA-1 compared with placebo did not reduce major adverse CV events (CV death, MI, or stroke) through 90 days. The suggestion of benefit among those with elevated baseline LDL-C is hypothesis generating.

References:

Gibson CM, Duffy D, Korjian S, et al., on behalf of the AEGIS-II Committees and Investigators. Apolipoprotein A1 Infusions and Cardiovascular Outcomes After Acute Myocardial Infarction. N Engl J Med 2024;Apr 6:[Epub ahead of print].

Editorial: Ballantyne CM, Nambi V. HDL Therapeutics — Time for a Curtain Call or Time to Reconceptualize? N Engl J Med 2024;Apr 6:[Epub ahead of print].

Povsic TJ, Korjian S, Bahit MC, et al., on behalf of the AEGIS-II Committees and Investigators. Effect of CSL112 on Recurrent Myocardial Infarction and Cardiovascular Death: Insights From the AEGIS-II Trial. J Am Coll Cardiol 2024;Apr 6:[Epub ahead of print].

Presented by Dr. C. Michael Gibson at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 6, 2024.

Clinical Topics: Acute Coronary Syndromes, Vascular Medicine

Keywords: ACC24, ACC Annual Scientific Session, Acute Coronary Syndrome, Myocardial Infarction, Novel Agents, Stroke


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