Alirocumab Safety Profile Similar Regardless of MI, Ischemic Stroke Status

Illustration of a blocked artery.

In patients with prior myocardial infarction (MI)/ischemic stroke, treatment with alirocumab is associated with a reduction in low-density lipoprotein cholesterol (LDL-C), as well as reductions in lipoprotein(a), apolipoprotein B, and non-high-density lipoprotein cholesterol (non-HDL-C), according to study results published in the Journal of Clinical Lipidology. In addition, efficacy and safety results were similar in patients without prior MI/ischemic stroke.

Patient-level data were obtained from 9 phase 3 ODYSSEY trials (range of duration, 24-104 weeks) for the analysis. The trial cohorts included patients with either heterozygous familial hypercholesterolemia (FH) and/or non-FH, as well as established coronary heart disease or cardiovascular risk factors (n = 4880). In the pooled cohort, patients were treated with alirocumab 75 mg/150 mg or 150 mg every 2 weeks. Alirocumab was given primarily on background statins with or without other lipid-lowering therapies. Statin status, alirocumab dose, and placebo or ezetimibe controls were included in the analyses.

Compared with patients with prior MI/ischemic stroke, patients without prior MI/ischemic stroke had higher mean total PCSK9 (673.3 ng/mL vs 707.3 ng/mL, respectively; P <.0006) and lipid/lipoprotein levels (LDL-C [116.5 mg/dL vs 133.2 mg/dL, respectively], non-HDL-C [146.0 mg/dL vs 162.8 mg/dL, respectively], HDL-C [48.4 mg/dL vs 50.4 mg/dL], apoB [98.4 mg/dL vs 107.6 mg/dL, respectively]; P <.0001 for all). Comparatively, the median lipoprotein(a) was higher in patients with prior MI/ischemic stroke (25.6 mg/dL vs 23.0 mg/dL; P =.0058).

From baseline to 24 weeks, there was a reduction in LDL-C levels in patients with and without prior MI/ischemic stroke (51.1%-62.9% vs 43.6%-58.3%, respectively; P =.1485). Treatment with alirocumab was associated with reductions in other lipid/lipoproteins in both groups from baseline to 24-week follow-up, including lipoprotein(a).

A greater percentage of alirocumab-treated patients who received background statin therapy achieved their LDL-C target levels at 24 weeks (patients with prior MI/ischemic stroke [74.1%-84.8%] and patients without prior MI/ischemic stroke [63.7%-74.7%]) compared with patients who received placebo (4.5%-9.0% and 2.3%-6.7%, respectively) or ezetimibe (51.4% and 45.7%, respectively) (P <.0001 for all). Alirocumab was well tolerated, and safety outcomes were consistent in patients with and without prior MI/ischemic stroke.

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A study limitation was the lack of assessment of whether there was a direct treatment effect of alirocumab on cardiovascular outcomes.

According to the study investigators, the findings “suggest that PCSK9 inhibition may benefit patients who have had an MI and/or an ischemic stroke and are at very high risk of recurrent cardiovascular events.”


The study was funded by Sanofi and Regeneron Pharmaceuticals, Inc. Multiple authors disclosed relationships with pharmaceutical companies.

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Bruckert E, Kereiakes DJ, Koren MJ, et al. PCSK9 inhibition in patients with and without prior myocardial infarction or ischemic stroke: a pooled analysis of nine randomized-controlled studies of alirocumab [published online April 10, 2019]. J Clin Lipidol. doi:10.1016/j.jacl.2019.04.005

This article originally appeared on The Cardiology Advisor