CSL112, a plasma-derived apolipoprotein A1, is a component of high-density lipoprotein cholesterol (HDL-C), also known as “good cholesterol”. CSL112 removes plaque from the arteries, and helps facilitate the removal process of low-density lipoprotein cholesterol (LDL-C), the “bad cholesterol”, from the body. The AEGIS-II trial found that CSL112 did not significantly reduce recurrent cardiovascular events compared to placebo in patients with an acute myocardial infarction (MI), multivessel coronary artery disease, and other cardiovascular risk factors. However, two recent secondary analyses sought to expand on the primary findings of the trial and suggest a potential benefit of CSL112.
CSL112 and Total Ischemic Event Burden
The primary outcome of the AEGIS-II trial, a time-to-first-event analysis of a composite endpoint of cardiovascular death, MI, or stroke within 90 days, may not fully capture the intervention’s clinical impact due to the potential for multiple events. Accordingly, a prespecified exploratory analysis in the Journal of the American College of Cardiology examined CSL112’s effect on the total burden of nonfatal ischemic events (recurrent MI and stroke) and cardiovascular death. Among AEGIS-II patients at high risk for recurrent cardiovascular events, researchers found that four weekly infusions of CSL112 were associated with a statistically significant reduction in the total burden of nonfatal ischemic events and cardiovascular death during the first year post-acute MI.
Impact of Baseline LDL-C on CSL112 Efficacy
Given the established link between higher LDL-C and atherosclerosis (plaque buildup in the arteries), and the observed greater absolute benefit of PCSK9 inhibitors in patients with baseline LDL-C of 100 mg/dL or greater receiving statin therapy, a post-hoc analysis in the European Heart Journal investigated the impact of baseline LDL-C on the efficacy of CSL112 in the AEGIS-II patient population. The analysis revealed that CSL112 significantly decreased the risk of recurrent cardiovascular events compared to placebo in patients with baseline LDL-C levels of 100 mg/dL or greater. In contrast, no significant difference in cardiovascular events was seen between the CSL112 and placebo groups for patients with baseline LDL-C under 100 mg/dL. Further studies are needed to determine if and how baseline LDL-C influences the efficacy of CSL112.
These studies were conducted on behalf of the AEGIS-II Committees and Investigators, and CVC co-authors include Drs. Shaun Goodman (Executive Steering Committee) and Kevin Bainey (Canadian National Leader and Steering Committee). The CVC, with the clinical operations leadership of Tracy Temple and Lyndsey Garritty, coordinated Canadian site participation in the AEGIS-II trial.
