AEGIS-II: Negative primary endpoint but infusions might benefit subgroups of patients

Infusions with human apolipoprotein A-1 (ApoA-I) failed to achieve a significant reduction in major adverse cardiovascular events (MACE) in patients with myocardial infarction (MI) and additional risk factors. However, the infusions might still have a potential in patients with high LDL levels.

ApoA-I, the main component of HDL cholesterol, stabilises vulnerable plaques by mediating reverse cholesterol efflux. In the previous AEGIS-I trial, a single infusion of purified human ApoA-1 (CSL112) increased cholesterol efflux in the setting of MI [1]. The AEGIS-II trial (NCT03473223), presented by Prof. Michael Gibson (Harvard Medical School, MA, USA), enrolled 18,219 participants who had been hospitalised for an MI [2]. All participants had multivessel disease and additional cardiovascular risk factors. They were randomly assigned to receive infusions of either CSL112 or a placebo for 4 weeks, with the first infusion given within 5 days of hospitalisation. The study’s primary endpoint was the time to the first occurrence of MACE (i.e. MI, stroke, or cardiovascular death) at 90 days.

At 90 days, participants treated with CSL112 had a 4.9% reduction of MACE compared with 5.2% in the placebo group, a difference that was not statistically significant. In an exploratory analysis, the researchers included participants whose LDL cholesterol level was ≥100 mg/dl at study entry despite statin therapy. These participants experienced a 30% decrease in the primary endpoint, a statistically significant finding, whereas participants whose LDL cholesterol at study entry was less than 100 mg/dL saw no reduction in the primary endpoint. “LDL at baseline modulated the treatment effect; the magnitude of treatment effect increased with the LDL concentrations” Prof. Gibson commented. The agent was well tolerated.

The benefit of ApoA-1 infusions in hyperlipidaemic patients is biologically plausible, but Prof. Gibson emphasised that this observation is hypothesis-generating and requires prospective validation in further studies.

1. 
   
   1. Gibson CM, et al. 2016;134:1918–1930.
   2. Gibson CM, et al. CSL112 (Apolipoprotein A-I) Infusions And Cardiovascular Outcomes In Patients With Acute Myocardial Infarction (ApoA-I Event Reducing In Ischemic Syndromes II (AEGIS-II) Trial): Primary Trial Results. LB1, Session 402, ACC 2024 Scientific Session, 6–8 April, Atlanta, USA.

Medical writing support was provided by Karin Drooff, MPH.
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Posted on 10 April, 202410 April, 2024