The total number of nonfatal cardiovascular (CV) events and deaths prevented with alirocumab use was approximately double the number of first events prevented after acute coronary syndrome (ACS), according to findings from the ODYSSEY Outcomes trial (ClinicalTrials.gov identifier: NCT01663402) published in the Journal of the American College of Cardiology.
Given these findings, researchers suggest that total CV event reduction may represent a more comprehensive metric to assess alirocumab clinical efficacy after ACS.
Individuals aged ≥40 years who had been hospitalized for ACS between 1 and 12 months before study randomization were eligible for enrollment. All patients presented with a low-density lipoprotein cholesterol level of ≥70 mg/dL, a non-high-density lipoprotein cholesterol level of ≥100 mg/dL (2.59 mmol/L), or an apolipoprotein B level of ≥80 mg/dL.
Study investigators randomly assigned patients to receive either 75 mg alirocumab (n=9462) or placebo (n=9462) and then compared the 2 groups in terms of the incidence of nonfatal CV events and death.
Doses of the alirocumab were administered every 2 weeks via subcutaneous injection. The first occurrence of nonfatal myocardial infarction, coronary disease death, fatal and nonfatal ischemic stroke, or unstable angina necessitating hospitalization made up the primary efficacy endpoint.
Hemorrhagic stroke, heart failure requiring hospitalization, and ischemia-driven coronary revascularization defined the nonfatal CV events in this analysis.
A total of 5425 nonfatal CV events or deaths occurred during the median 2.8-year follow-up. Of these events, a total of 3064 were first events. After randomization and subsequent treatment, the researchers observed 190 fewer first and 385 fewer total nonfatal CV events and deaths in patients treated with alirocumab vs placebo.
Compared with placebo, significant reductions were observed with alirocumab for total nonfatal CV events (hazard ratio [HR], 0.87; 95% CI, 0.82-0.93) and death (HR, 0.83; 95% CI, 0.71-0.97).
The researchers explained that their analysis may be limited by the lack of inclusion of relevant patient characteristics that could have contributed to the “apparent relationship between nonfatal cardiovascular events and death.”
Findings from this trial suggest that a “reduction in total nonfatal and fatal events may be viewed as a preferred metric to summarize the clinical benefit and efficiency of treatment with alirocumab.”
Disclosures: This study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Please refer to the journal article for a full list of author disclosures.
Szarek M, White HD, Schwartz GG, et al. Alirocumab reduces total nonfatal cardiovascular and fatal events in the ODYSSEY OUTCOMES trial [published online November 11, 2018]. JACC. doi: 10.1016/j.jacc.2018.10.039