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Infusions with human apolipoprotein A-1 failed to significantly reduce major adverse cardiovascular events in patients with myocardial infarction.
Infusions with human apolipoprotein A-1 (ApoA-I) failed to significantly reduce major adverse cardiovascular events (MACE) in patients with myocardial infarction (MI) and additional risk factors. However, the infusions might still have potential in patients with high LDL levels.
ApoA-I, the main component of HDL cholesterol, stabilizes 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 C. Michael Gibson, MD, MS, enrolled 18,219 participants who had been hospitalized for 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 hospitalization. The study’s primary endpoint was the time to the first occurrence of MACE (ie, 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 at least 100 mg/dl at study entry despite statin therapy. These participants experienced a 30% reduction 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” Dr. Gibson commented. The agent was well tolerated.
The benefit of ApoA-1 infusions in hyperlipidemic patients is biologically plausible, but Dr. Gibson emphasized that this observation is hypothesis-generating and requires prospective validation in further studies.
Medical writing support was provided by Karin Drooff, MPH.
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