KEY POINTS:
- In this exploratory analysis of the AEGIS-II randomized control trial, the authors compare the rates of stroke, myocardial infarction and death at 90 days between patients with hyperlipidemia who receive ApoA-I infusions (CSL112) versus placebo after presentation with acute myocardial infarction
- In patients with hyperlipidemia and LDL cholesterol ≥ 100 mg/dL who present with acute myocardial infarction, the infusion of ApoA-I may result in lower rates of major adverse cardiovascular events
Although scientists have previously demonstrated an association between higher HDL and fewer cardiovascular events, no prior studies have demonstrated fewer cardiovascular events in association with therapies that increase HDL. The lack of benefit of HDL raising therapies has been thought to be due to variability in the capacity of HDL molecules to remove cholesterol, also known as cholesterol efflux capacity. In the previously-published AEGIS-II trial, > 18,000 patients who presented with acute myocardial infarction (AMI) were randomized to receive ApoA-I, the primary functional component of HDL, versus placebo. In the primary analysis of the AEGIS-II trial, the authors found no difference in the primary endpoint of cardiovascular death, myocardial infarction, and stroke at 90 days. In this exploratory secondary analysis, the authors focus specifically on patients with hyperlipidemia and ask the same question – does the infusion of ApoA-I result in lower rates of the primary outcome, cardiovascular death, myocardial infarction, and stroke, at 90 days?
In this study, the authors hypothesize that there will be a greater benefit for ApoA-I infusion in those individuals who have a higher LDL cholesterol at baseline, analogous to the greater LDL-lowering benefit of PCSK-9 inhibitors in patients with a baseline LDL greater than 100 mg/dL. In the full sample of patients from the AEGIS-II trial, the median total cholesterol was approximately 160 mg/dL with a median LDL cholesterol of 84 mg/dL and median HDL cholesterol of 39 mg/dL.
Overall, 18,219 patients with acute MI, multivessel coronary artery disease, and additional risk factors were randomized to either four weekly infusions of 6 g CSL112 or placebo. This exploratory post-hoc analysis evaluated cardiovascular outcomes by baseline LDL-C in patients prescribed guideline-directed statin therapy at the time of randomization (n=15,731). The hazard ratio for the primary outcome, cardiovascular death, myocardial infarction, and stroke at 90 days, was modeled as a function of LDL as a continuous variable. Individuals with an LDL ≥ 100 mg/dL were compared to those with an LDL < 100 mg/dL using a Cox proportional-hazards regression model adjusting for covariates including treatment, geographic region, index myocardial infarction type, index myocardial infarction management, age, diabetes, and peripheral artery disease. Not surprisingly, individuals with an LDL ≥ 100 mg/dL had lower rates of statin use (31.6% vs. 58.3%) and lower rates of non-statin lipid-lowering medications (3.5% vs. 8.0%) prior to their index acute myocardial infarction. Furthermore, those with an LDL ≥ 100 mg/dL were more likely to be current smokers, and less likely to have hypertension, a prior MI or prior coronary revascularization. When comparing those with a baseline LDL ≥ 100 mg/dL to those below 100 mg/dL, there was a significant reduction in the rates of stroke, myocardial infarction and death at 90 days, 180 days, and 365 days. At 90 days, the number needed to treat for individuals with an LDL ≥ 100 mg/dL, was 66 individuals.
Put into context, Dr. Gibson shares “if you think of HDL cholesterol as a garbage truck, you have to have garbage to take out to have a benefit.” Future randomized trials focused specifically on individuals with LDL ≥ 100 mg/dL are needed to explore these findings further.