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

• DOI: 10.1161/circulationaha.119.044434
• Publication Date: 2019-11-11T10:03:53Z
• Authors: Amy Damask; P. Gabriel Steg; Gregory G. Schwartz; Michael Szarek; Emil Hagström; Lina Badimon; M. John Chapman; Catherine Boileau; Sotirios Tsimikas; Henry N. Ginsberg; Poulabi Banerjee; Garen Manvelian; Robert Pordy; Sibylle Hess; John D. Overton; Luca A. Lotta; George D. Yancopo...; Goncalo R. Abecasis; Aris Baras; Charles Paulding
• Keywords: Alirocumab; PCSK9; Mace; Post-hoc analysis

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 Acute Coronary Syndrome During Treatment With Alirocumab). In this study, higher baseline levels 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 who derive increased statins. We performed post hoc analyses to determine whether PRS CAD identifies higher-risk individuals, independent LDL-C other known factors, might Methods: a randomized, double-blind, placebo-controlled comparing or placebo 18 924 patients acute syndrome elevated atherogenic lipoproteins despite optimized statin The primary endpoint comprised CAD, nonfatal myocardial infarction, ischemic stroke, unstable angina requiring hospitalization. A genome-wide comprising 6 579 025 genetic variants evaluated 11 953 available DNA samples. Analysis MACE placebo-treated patients, whereas treatment analysis all patients. Results: incidence group related CAD: 17.0% (>90th percentile) 11.4% lower (≤90th percentile; P <0.001); relationship not explained by established factors. Both absolute relative reduction compared versus low There groups 6.0% 1.5%, respectively, 37% (hazard ratio, 0.63 [95% CI, 0.46–0.86]; =0.004) 13% 0.87 0.78–0.98]; =0.022; interaction =0.04). Conclusions: is recurrent after larger treatment, providing tool stratification precision medicine.