Weekly Journal Scan: apolipoprotein A1 is not an adequate shield against early vascular events after acute myocardial infarction

Key points• The ApoA-I Event Reducing in Ischemic Syndromes II (AEGIS-II) study is a company-funded, double-blind, placebo-controlled trial.The aim was to study the efficacy and safety of human plasma-derived apolipoprotein A1 (CSL112) in reducing the risk of major adverse cardiovascular events (MACEs) in the 90-day high-risk period after an acute myocardial infarction (AMI). 1 • Patients were required to have Type 1 AMI, multivessel coronary artery disease, and additional cardiovascular (CV) risk factors (pharmacologic treatment for diabetes or ≥2 of the following: age ≥65 years, a history of MI, or peripheral artery disease) and were randomly assigned to receive four weekly 2-h infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for AMI.• The primary efficacy endpoint was a composite of MI, stroke, or death from CV causes from randomization through 90 days.Key secondary endpoints included the total number of hospitalizations for coronary, cerebral, or peripheral ischaemia from the time of randomization through 90 days; the composite of MI, stroke, or CV death through 180 and 365 days; and the cumulative incidence of the individual components of the composite primary endpoint through 365 days.All assessments were performed in a time-to-first-event analysis.• A total of 18 226 patients underwent randomization in 49 countries, from March 2018 to November 2022 (mean age, 65.5 years; 74% men; 51% with ST-segment elevation myocardial infarction as index event; two-thirds had diabetes and a similar percentage had hypercholesterolaemia, while 80% had hypertension; 88% had undergone percutaneous coronary intervention; 93% received dual antiplatelet therapy; 93% received statins; and 76% received high-intensity statin therapy).The 90-day follow-up and primary endpoint ascertainment were completed for 99% of participants.The percentage of patients who underwent randomization but did not receive CSL112 or placebo was about 1%, and all four infusions were received by 90% of patients in both groups.• No significant difference was observed in the primary endpoint at 90 days 439 patients (4.8%) in the CSL112 group vs. 472 patients (5.2%) in the placebo group; hazard ratio (HR), 0.93; 95% confidence interval (CI), 0.81-1.05;P = .24,at 180 days (6.9% vs. 7.6%; HR, 0.91; 95% CI, 0.81-1.01),or at 365 days of follow-up (9.8% vs. 10.5%;HR, 0.93; 95% CI, 0.85-1.02).These results were consistent across multiple subgroups.Administration of CSL112 appeared safe with a similar proportion of subjects experiencing adverse events in both treatment arms.The number of patients with hypersensitivity or anaphylactoid reactions that resulted in discontinuation of the investigational regimen was low but higher in the CSL112 compared to the placebo group (14 vs. 4 patients; P = .02).