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
| Autor: | Sibylle Hess, Charles Paulding, Catherine Boileau, M. John Chapman, Luca A. Lotta, Garen Manvelian, George D. Yancopoulos, Michael Szarek, Gonçalo R. Abecasis, Emil Hagström, Aris Baras, Sotirios Tsimikas, Robert Pordy, Henry N. Ginsberg, Amy Damask, P. Gabriel Steg, Poulabi Banerjee, Gregory G. Schwartz, Lina Badimon, John D. Overton |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Multifactorial Inheritance medicine.medical_specialty polygenic inheritance Hypercholesterolemia Coronary Artery Disease 030204 cardiovascular system & hematology Antibodies Monoclonal Humanized Coronary artery disease 03 medical and health sciences 0302 clinical medicine Double-Blind Method Risk Factors cardiovascular disease Physiology (medical) Internal medicine genomics medicine Humans risk factors genetics cardiovascular diseases subtilisin-kexin type 9 Aged Proportional Hazards Models 030304 developmental biology Alirocumab pharmacogenomics 0303 health sciences business.industry Anticholesteremic Agents PCSK9 PCSK9 Inhibitors Cholesterol LDL Middle Aged Placebo Effect Proprotein convertase medicine.disease Cardiovascular Diseases Pharmacogenomics proprotein convertase Kexin Female Polygenic risk score Hydroxymethylglutaryl-CoA Reductase Inhibitors Proprotein Convertase 9 Cardiology and Cardiovascular Medicine business Mace |
| Zdroj: | CIRCULATION r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau instname |
| ISSN: | 1524-4539 0009-7322 |
| Popis: | 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. Results: The incidence of MACE in the placebo group was related to PRS for CAD: 17.0% for high PRS patients (>90th percentile) and 11.4% for lower PRS patients (≤90th percentile; P P =0.004) versus a 13% reduction in the low PRS group (hazard ratio, 0.87 [95% CI, 0.78–0.98]; P =0.022; interaction P =0.04). Conclusions: A high PRS for CAD is associated with elevated risk for recurrent MACE after acute coronary syndrome and a larger absolute and relative risk reduction with alirocumab treatment, providing an independent tool for risk stratification and precision medicine. |
| Databáze: | OpenAIRE |
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