Infusion of human apolipoprotein A1 fails to reduce cardiovascular events in acute MI patients: NEJM

A recent international clinical trial by C. Michael Gibson and colleagues investigated the efficacy of CSL112 (human Apolipoprotein A1) which helps in reducing the risk of recurrent cardiovascular events in patients who have experienced acute myocardial infarction. The findings were published in The New England Journal of Medicine  and highlight the potential of CSL112 to improve the patient outcomes following such critical cardiac events.

This double-blind, placebo-controlled trial enrolled a substantial group with a total of 18,219 patients who underwent acute myocardial infarction, multivessel coronary artery disease and additional cardiovascular risk factors. The participants were randomly assigned to receive either four weekly infusions of 6 grams of CSL112 or a matching placebo where the first infusion was administered within five days after the initial medical contact for the heart attack.

Despite the promising premise of CSL112, the results of the trial found that over the 90-day follow-up period, there was no significant difference observed between the CSL112 group and the placebo group in terms of the primary endpoint, which is a composite of myocardial infarction, stroke or death from cardiovascular causes. This lack of divergence persisted throughout the 180-day and 365-day follow-up periods as well.

Also, the data revealed that 4.8% of patients in the CSL112 group experienced primary endpoint events at 90 days when compared to the 5.2% in the placebo group. At 180 days, the rates were 6.9% against 7.6%, and at 365 days, 9.8% against 10.5%, respectively. It is important to note that the percentages of adverse events were comparable between the two groups, although an increased number of hypersensitivity events were reported in the CSL112 group.

This comprehensive investigation suggests that among patients with acute myocardial infarction, multivessel coronary artery disease and additional cardiovascular risk factors, the administration of four weekly infusions of CSL112 did not lower the risk of myocardial infarction, stroke or death from cardiovascular causes when compared to placebo over a 90-day period.

While these results may come as a setback for post-myocardial infarction care, it helps in understanding the complexities involved in addressing recurrent cardiovascular events. Further research and development efforts are warranted to explore alternative strategies or refine existing approaches to improve patient outcomes and reduce the burden of cardiovascular disease.

Reference:

Gibson, C. M., Duffy, D., Korjian, S., Bahit, M. C., Chi, G., Alexander, J. H., Lincoff, A. M., Heise, M., Tricoci, P., Deckelbaum, L. I., Mears, S. J., Nicolau, J. C., Lopes, R. D., Merkely, B., Lewis, B. S., Cornel, J. H., Trebacz, J., Parkhomenko, A., Libby, P., … Harrington, R. A. (2024). Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction. In New England Journal of Medicine. Massachusetts Medical Society. https://doi.org/10.1056/nejmoa2400969