Background Cardiovascular events frequently recur after acute myocardial infarction,
and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the
main protein in high-density lipoprotein - has been associated with an increased risk
of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that
increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the
risk of recurrent cardiovascular events after acute myocardial infarction is unclear.Methods
We conducted an international, double-blind, placebo-controlled trial involving patients
with acute myocardial infarction, multivessel coronary artery disease, and additional
cardiovascular risk factors. Patients were randomly assigned to receive either four
weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered
within 5 days after the first medical contact for the acute myocardial infarction.
The primary end point was a composite of myocardial infarction, stroke, or death from
cardiovascular causes from randomization through 90 days of follow-up.Results A total
of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in
the placebo group). There was no significant difference between the groups in the
risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in
the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93;
95% confidence interval [CI], 0.81 to 1.05; P=0.24), at 180 days of follow-up (622
patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01),
or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard
ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events
was similar in the two groups; a higher number of hypersensitivity events was reported
in the CSL112 group.Conclusions Among patients with acute myocardial infarction, multivessel
coronary artery disease, and additional cardiovascular risk factors, four weekly infusions
of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death
from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II
ClinicalTrials.gov number, NCT03473223.) In patients with acute MI, multivessel coronary
artery disease, and other cardiovascular risk factors, CSL112 did not reduce the risk
of MI, stroke, or death from cardiovascular causes.
