Alirocumab Safety Profile Similar Regardless of MI, Ischemic Stroke Status

Cholesterol plaque, ACS
Cholesterol plaque, ACS

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.

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

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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.


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