Related Experiment Video
Updated: Jun 29, 2025
Improvement of a Closed Chest Porcine Myocardial Infarction Model by Standardization of Tissue and Blood Sampling Procedures
Published on: March 12, 2018
Effect of Reconstituted Human Apolipoprotein A-I on Recurrent Ischemic Events in Survivors of Acute MI
Thomas J Povsic1, Serge Korjian2, M Cecilia Bahit3
1Duke Clinical Research Institute/Duke University Medical Center, Durham, North Carolina, USA.
Insights
CSL112, an apolipoprotein A-I infusion, showed numerically lower rates of cardiovascular death and myocardial infarction in high-risk patients. Further studies are needed to confirm CSL112's potential role in reducing plaque disruption events.
Area of Science:
- Cardiology
- Vascular Biology
- Pharmacology
Background:
- The AEGIS-II trial investigated CSL112 (intravenous human apolipoprotein A-I) for reducing recurrent myocardial infarction (MI) in high-risk patients.
- The hypothesis centered on CSL112's potential to decrease plaque disruption and subsequent cardiovascular events.
Purpose of the Study:
- To explore the impact of CSL112 therapy on the incidence of cardiovascular death and recurrent MI.
- This analysis aimed to evaluate CSL112's efficacy in a high-risk MI population.
Main Methods:
- AEGIS-II was an international, randomized, double-blind, placebo-controlled trial involving 18,219 high-risk acute MI patients.
- Participants received four weekly infusions of either CSL112 (6 g apoA-I) or a placebo.
Main Results:
- The composite of cardiovascular death and type 1 MI showed a trend towards reduction with CSL112 (e.g., HR 0.86, P=0.048 at 180 days).
- Rates of cardiovascular death or any MI were numerically lower in the CSL112 group throughout follow-up.
- CSL112 demonstrated a notable effect on type 1 MI and MI due to stent thrombosis (type 4b).
Conclusions:
- CSL112 did not meet statistical significance for primary endpoints but showed numerically lower rates of CV death and MI.
- Findings suggest apolipoprotein A-I may reduce plaque disruption via enhanced cholesterol efflux.
- Further prospective research is warranted to validate these observations and CSL112's role.
Background:
The AEGIS-II trial hypothesized that CSL112, an intravenous formulation of human apoA-I, would lower the risk of plaque disruption, decreasing the risk of recurrent events such as myocardial infarction (MI) among high-risk patients with MI.
Objectives:
This exploratory analysis evaluates the effect of CSL112 therapy on the incidence of cardiovascular (CV) death and recurrent MI.
Methods:
The AEGIS-II trial was an international, multicenter, randomized, double-blind, placebo-controlled trial that randomized 18,219 high-risk acute MI patients to 4 weekly infusions of apoA-I (6 g CSL112) or placebo.
Results:
The incidence of the composite of CV death and type 1 MI was 11% to 16% lower in the CSL112 group over the study period (HR: 0.84; 95% CI: 0.7-1.0; P = 0.056 at day 90; HR: 0.86; 95% CI: 0.74-0.99; P = 0.048 at day 180; and HR: 0.89; 95% CI: 0.79-1.01; P = 0.07 at day 365). Similarly, the incidence of CV death or any MI was numerically lower in CSL112-treated patients throughout the follow-up period (HR: 0.92; 95% CI: 0.80-1.05 at day 90, HR: 0.89; 95% CI: 0.79-0.996 at day 180, HR: 0.91; 95% CI: 0.83-1.01 at day 365). The effect of CSL112 treatment on MI was predominantly observed for type 1 MI and type 4b (MI due to stent thrombosis).
Conclusions:
Although CSL112 did not significantly reduce the occurrence of the primary study endpoints, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis-related MI compared with placebo. These findings could suggest a role of apoA-I in reducing subsequent plaque disruption events via enhanced cholesterol efflux. Further prospective data would be needed to confirm these observations.
