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

作者：Vera Bittner, Michael Szarek, Philip E. Aylward, Deepak L. Bhatt, Rafael Díaz, 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, Robert A. Vogel, Harvey D. White, Doron Zahger, Andreas M. Zeiher, Philippe Gabríel Steg, Gregory G. Schwartz · 发表于：Journal of the American College of Cardiology · 年份：2020 · DOI：10.1016/j.jacc.2019.10.057 · 被引用次数：597 · 研究领域：Lipoproteins and Cardiovascular Health、Protease and Inhibitor Mechanisms、Antiplatelet Therapy and Cardiovascular Diseases

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 demogra...