Long-Term Safety and Efficacy of Alirocumab in Patients Post-Acute Coronary Syndrome

Although lipid-lowering therapy is frequently used as a long-term (typically lifetime) intervention to reduce cardiovascular risk, research on the efficacy and safety of this treatment strategy is often limited to the relatively short time frame of clinical trials (typically 2-5 years). 

Alirocumab is an injectable monoclonal antibody directed against proprotein convertase subtilisin/kexin type 9 (PCSK9) that reduces the level of low-density lipoprotein-cholesterol (LDL-C) and other atherogenic lipoproteins. The ODYSSEY OUTCOMES trial, led in Canada by the CVC, enrolling 361 patients from 48 sites, sought to compare the effect of alirocumab with placebo in 18,924 patients with a recent acute coronary syndrome (ACS), including myocardial infarction 4-52 weeks prior, who were mostly receiving high-intensity statin, and were followed up for a period of up to 5 years. This secondary analysis, presented in 2022 at the European Society of Cardiology Congress, and recently published in the Journal of the American Heart Association, examined the efficacy, safety, and tolerability of alirocumab compared to placebo in a subgroup of patients eligible for 3 to 5 years of follow-up. 

Of the 8,242 patients eligible for 3 to 5 years’ follow‐up, 8,228 received 1 or more dose(s) of study medication, accounting for 24,610 patient‐years of observation, with a median follow‐up of 3.3 years; 6,651 patients were eligible for 3 to 4  years’ follow‐up, and 1,574 patients were eligible for 4 to 5 years’ follow‐up. This constitutes the longest randomized, placebo‐controlled comparison of PCSK9 inhibitors to date.

Dr. Shaun Goodman, CVC Co-Director, and Executive Steering Committee member and Canadian National Leader of the ODYSSEY OUTCOMES trial, concludes that: “Alirocumab reduced the risk of major adverse cardiovascular events and death after an ACS without differences in specific safety or overall adverse events. These benefits were observed in the context of substantial and sustained lowering of LDL-C with alirocumab versus placebo, and were consistent with those achieved with alirocumab in the overall trial population. Further, these findings are consistent with the Cholesterol Treatment Trialists meta-analyses of statins versus placebo, where progressively greater benefits were observed with longer duration of LDL-C lowering. Remarkably, the tolerability of alirocumab was indistinguishable from placebo except for a small excess of local injection-site reactions. Thus, alirocumab appears to be a safe, well-tolerated, and effective lipid-modifying and outcome-improving treatment when used for up to 5 years.”