The lowering of lipoprotein(a) with alirocumab was found to independently contribute to the reduction in major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS), according to a study published in the Journal of the American College of Cardiology.

In this analysis of the ODYSSEY Outcomes trial (Clinicaltrials.gov identifier: NCT01663402), patients aged ≥40 years who experienced ACS, 1 to 12 months before entering the study (n=18,924), and had a low-density lipoprotein cholesterol (LDL-C) level ≥70 mg/dL, a non-high-density lipoprotein cholesterol (non-HDL-C) level ≥100 mg/dL, or an apolipoprotein B level ≥80 mg/dL on high-intensity statin therapy were randomly assigned to receive alirocumab 75 mg every 2 weeks or matching placebo.

In patients receiving alirocumab who did not reach an LDL-C level <50 mg/dL, the dose was blindly increased to 150 mg. Placebo was blindly substituted for alirocumab in patients who had 2 consecutive LDL-C levels <15 mg/dL. Lipoprotein(a) mass was measured at randomization, and at 4 and 12 months. The primary endpoints were MACE, a composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization.

MACE was found to be predicted by lipoprotein(a) levels at baseline (median, 21.2 mg/dL; interquartile range [IQR], 6.7-59.6 mg/dL) and LDL-C. The occurrence of MACE and coronary heart disease death and/or nonfatal myocardial infarction was found to increase significantly from the lowest to the highest quartile of baseline lipoprotein(a) level. At 4 months, lipoprotein(a) concentrations were lower in patients receiving alirocumab vs placebo, with levels remaining stable at month 12. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR, 0-13.5 mg/dl), corrected LDL-C by 51.1 mg/dL (IQR, 33.7-67.2 mg/dL), and reduced the risk for MACE (hazard ratio, 0.85; 95% CI, 0.78-0.93).Study limitations include the variable cholesterol content in lipoprotein(a) particles, the fact that correction of LDL-C or non-HDL-C by 30% of lipoprotein(a) mass is an approximation of the contribution of cholesterol in lipoprotein(a). The mass thus measured, correlates imperfectly with molar concentration of lipoprotein(a) due to the influence of apolipoprotein(a) isoform size. In addition, changes in lipoprotein(a) may reflect adherence to study treatment and possibly general adherence to other evidence-based cardiovascular therapies and lifestyle modifications, which might affect the prognosis. “There is strong evidence that elevated lipoprotein(a) contributes to the incidence of coronary heart disease, but no treatment has yet been proven to reduce coronary risk through a reduction in lipoprotein(a),” the researchers concluded. “Our observations suggest that reduction of lipoprotein(a) contributed to the reduction of cardiovascular risk with alirocumab therapy, independent of the concurrent reduction of other atherogenic lipoproteins.”


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Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Bittner VA, Szarek M, Aylward PE, et al. Effect of alirocumab on lipoprotein(a) and cardiovascular risk after acute coronary syndrome. J Am Coll Cardiol. 2020;75(2):133-144.