Patients With High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit From Alirocumab Treatment in the ODYSSEY OUTCOMES Trial

作者：Amy Damask, Philippe Gabríel Steg, Gregory G. Schwartz, Michael J. Szarek, Emil Hagström, Lina Badimón, M. John Chapman, Cathérine Boileau, Sotirios Tsimikas, Henry N. Ginsberg, Poulabi Banerjee, Garen Z. Manvelian, Robert C. Pordy, Sibylle Hess, John D. Overton, Luca Andrea Lotta, George D. Yancopoulos, Gonçalo R. Abecasis, Aris Baras, Charles Paulding · 发表于：Circulation · 年份：2019 · DOI：10.1161/circulationaha.119.044434 · 被引用次数：252 · 研究领域：Lipoproteins and Cardiovascular Health、Genetic Associations and Epidemiology、Atherosclerosis and Cardiovascular Diseases

Background: Alirocumab, an antibody that blocks PCSK9 (proprotein convertase subtilisin/kexin type 9), was associated with reduced major adverse cardiovascular events (MACE) and death in the ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab). In this study, higher baseline levels of low-density lipoprotein cholesterol (LDL-C) predicted greater benefit from alirocumab treatment. Recent studies indicate high polygenic risk scores (PRS) for coronary artery disease (CAD) identify individuals at higher risk who derive increased benefit from statins. We performed post hoc analyses to determine whether high PRS for CAD identifies higher-risk individuals, independent of baseline LDL-C and other known risk factors, who might derive greater benefit from alirocumab treatment. Methods: ODYSSEY OUTCOMES was a randomized, double-blind, placebo-controlled trial comparing alirocumab or placebo in 18 924 patients with acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin treatment. The primary endpoint (MACE) comprised death of CAD, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. A genome-wide PRS for CAD comprising 6 579 025 genetic variants was evaluated in 11 953 patients with available DNA samples. Analysis of MACE risk was performed in placebo-treated patients, whereas treatment benefit analysis was performed in all patients. Result...