KEY POINTS:
- In this prespecified exploratory analysis of the AEGIS-II trial, the authors compare rates of recurrent myocardial infarction, stroke, and cardiovascular death up to 365 days among individuals who present with acute myocardial infarction and receive an infusion of ApoAI versus placebo
- Patients who had multiple events during the 365 day follow-up period were more likely to be older and have more cardiovascular comorbidities
- In this study, individuals who received ApoAI infusions had lower rates of major adverse cardiac events at 180 days with sustained benefit at 365 days compared to those who received placebo
In the previously published AEGIS-II trial, CSL112, a human plasma-derived version of apolipoprotein AI (ApoAI), the primary functional component of HDL, was compared to placebo to assess rates of the primary outcome, major adverse cardiac events (MACE), at 90 days. In this phase 3 randomized control trial, 18,219 patients who presented with acute myocardial infarction (AMI) were randomized to receive CSL112 versus placebo. In the primary analysis of this study, the authors found no difference in the first occurrence of MACE at 90 days between those who received CSL112 versus those who received placebo (4.8% vs. 5.2%) with a hazard ratio of 0.93 (CL 0.81-1.05). However, there are some limitations in the use of time to first event as the endpoint given the potential for individuals to experience multiple events.
In this prespecified exploratory analysis of the dataset from the AEGIS-II trial, the authors evaluate the effect of CSL112 on the total burden of events, including the rates of recurrent myocardial infarction, stroke, and CV death up to 365 days. When comparing the baseline characteristics of individuals who had one event versus multiple events during the follow-up period, those who had multiple events were more likely to be older and have a higher prevalence of cardiovascular comorbidities such as peripheral artery disease and myocardial infarction. Those with multiple events were also more likely to have presented with non-ST elevation myocardial infarction, have moderate renal impairment, and not have been on statin therapy. The authors found a reduction in MACE at 180 days (RR: 0.87, CI: 0.77-0.99, p =0.04) that was sustained at 365 days (RR: 0.89, CI: 0.80- 0.99, p=0.04). Approximately 70% of the observed events were recurrent myocardial infarction. It will be important for future trials to be powered specifically for the endpoint of total MACE, instead of time to first event, in order to further evaluate this exploratory finding.