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

Nov 26, 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:
11/18/2024
Date Updated:
11/26/2024
Original Posted Date:
04/06/2024
References

Contribution To Literature:

Highlighted text has been updated as of November 26, 2024.

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).
  • Total events defined as CV death, MI, and stroke (apoA-1 infusion vs. placebo):
    • 90 days: hazard ratio (HR) 0.88 (95% confidence interval [CI] 0.76-1.03), p = 0.11
    • 180 days: HR 0.87 (95% CI 0.77-0.99), p = 0.04
    • 365 days: HR 0.89 (95% CI 0.80-0.99), p = 0.04

Outcomes according to baseline LDL-C level:

  • LDL-C ≥100 mg/dL: CSL112 was associated with a reduction in CV death, MI, or stroke vs. placebo at 12 months (HR 0.78, 95% CI 0.65-0.93)
  • LDL-C <100 mg/dL: CSL112 was not associated with a reduction in CV death, MI, or stroke vs. placebo at 12 months (HR 0.96, 95% CI 0.85-1.08)

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 and deserves further evaluation. In a prespecified exploratory analysis, total CV events were marginally reduced with apoA-1 versus placebo.

References:

Gibson CM, Chi G, Duffy D, et al., on behalf of the AEGIS-II Committees and Investigators. ApoA-I Infusions and Burden of Ischemic Events After Acute Myocardial Infarction: Insights From the AEGIS-II Trial. J Am Coll Cardiol 2024;84:2185-92.

Editorial Comment: Blaha MJ, DeFilippis AP. Exploring the Need for Precise Myocardial Infarction Adjudication in Clinical Trials. J Am Coll Cardiol 2024;84:2193-5.

Gibson CM, Duffy D, Bahit MC, et al., for the AEGIS-II Committees and Investigators. Apolipoprotein A-I Infusions and Cardiovascular Outcomes in Acute Myocardial Infarction According to Baseline LDL-Cholesterol Levels: The AEGIS-II Trial. Eur Heart J 2024;Sep 2:[Epub ahead of print].

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;390:1560-71.

Editorial: Ballantyne CM, Nambi V. HDL Therapeutics — Time for a Curtain Call or Time to Reconceptualize? N Engl J Med 2024;390:1622-3.

Povsic TJ, Korjian S, Bahit MC, et al., on behalf of the AEGIS-II Committees and Investigators. Effect of Reconstituted Human Apolipoprotein A-I on Recurrent Ischemic Events in Survivors of Acute MI. J Am Coll Cardiol 2024;83:2163-74.

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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