Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome

ODYSSEY OUTCOMES Committees and Investigators, Vera A. Bittner, Michael Szarek, Phil Aylward, Deepak L. Bhatt, Rafael Diaz, Jay M. Edelberg, Zlatko Fras, Shaun G. Goodman, Sigrun Halvorsen, Corinne Hanotin, Robert A. Harrington, J. Wouter Jukema, Virginie Loizeau, Patrick M. Moriarty, Angèle Moryusef, Robert Pordy, Matthew T. Roe, Peter Sinnaeve, Sotirios Tsimikas & 6 others Robert Vogel, Harvey D. White, Doron Zahger, Andreas M. Zeiher, Ph Gabriel Steg, Gregory G. Schwartz

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: Lipoprotein(a) concentration is associated with cardiovascular events. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor, lowers lipoprotein(a) and low-density lipoprotein cholesterol (LDL-C). Objectives: A pre-specified analysis of the placebo-controlled ODYSSEY Outcomes trial in patients with recent acute coronary syndrome (ACS) determined whether alirocumab-induced changes in lipoprotein(a) and LDL-C independently predicted major adverse cardiovascular events (MACE). Methods: One to 12 months after ACS, 18,924 patients on high-intensity statin therapy were randomized to alirocumab or placebo and followed for 2.8 years (median). Lipoprotein(a) was measured at randomization and 4 and 12 months thereafter. The primary MACE outcome was coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina. Results: Baseline lipoprotein(a) levels (median: 21.2 mg/dl; interquartile range [IQR]: 6.7 to 59.6 mg/dl) and LDL-C [corrected for cholesterol content in lipoprotein(a)] predicted MACE. Alirocumab reduced lipoprotein(a) by 5.0 mg/dl (IQR: 0 to 13.5 mg/dl), corrected LDL-C by 51.1 mg/dl (IQR: 33.7 to 67.2 mg/dl), and reduced the risk of MACE (hazard ratio [HR]: 0.85; 95% confidence interval [CI]: 0.78 to 0.93). Alirocumab-induced reductions of lipoprotein(a) and corrected LDL-C independently predicted lower risk of MACE, after adjustment for baseline concentrations of both lipoproteins and demographic and clinical characteristics. A 1-mg/dl reduction in lipoprotein(a) with alirocumab was associated with a HR of 0.994 (95% CI: 0.990 to 0.999; p = 0.0081). Conclusions: Baseline lipoprotein(a) and corrected LDL-C levels and their reductions by alirocumab predicted the risk of MACE after recent ACS. Lipoprotein(a) lowering by alirocumab is an independent contributor to MACE reduction, which suggests that lipoprotein(a) should be an independent treatment target after ACS. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402)

LanguageEnglish
Pages133-144
Number of pages12
JournalJournal of the American College of Cardiology
Volume75
Issue number2
DOIs
Publication statusPublished - 21 Jan 2020

Keywords

  • acute coronary syndromes
  • alirocumab
  • low-density lipoprotein cholesterol
  • major adverse cardiovascular events
  • proprotein convertase subtilisin/kexin type 9 inhibition

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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