{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T01:47:02Z","timestamp":1792547222714,"version":"4.5.0"},"reference-count":29,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2020,2,25]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>ODYSSEY OUTCOMES was a randomized, double-blind, placebo-controlled trial comparing alirocumab or placebo in 18\u2009924 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\u2009579\u2009025 genetic variants was evaluated in 11\u2009953 patients with available DNA samples. Analysis of MACE risk was performed in placebo-treated patients, whereas treatment benefit analysis was performed in all patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The incidence of MACE in the placebo group was related to PRS for CAD: 17.0% for high PRS patients (&gt;90th percentile) and 11.4% for lower PRS patients (\u226490th percentile;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001); this PRS relationship was not explained by baseline LDL-C or other established risk factors. Both the absolute and relative reduction of MACE by alirocumab compared with placebo was greater in high versus low PRS patients. There was an absolute reduction by alirocumab in high versus low PRS groups of 6.0% and 1.5%, respectively, and a relative risk reduction by alirocumab of 37% in the high PRS group (hazard ratio, 0.63 [95% CI, 0.46\u20130.86];\n                      <jats:italic>P<\/jats:italic>\n                      =0.004) versus a 13% reduction in the low PRS group (hazard ratio, 0.87 [95% CI, 0.78\u20130.98];\n                      <jats:italic>P<\/jats:italic>\n                      =0.022; interaction\n                      <jats:italic>P<\/jats:italic>\n                      =0.04).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.119.044434","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T05:03:53Z","timestamp":1573448633000},"page":"624-636","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":236,"title":["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"],"prefix":"10.1161","volume":"141","author":[{"given":"Amy","family":"Damask","sequence":"first","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. Gabriel","family":"Steg","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, H\u00f4pital Bichat, Assistance Publique-H\u00f4pitaux de Paris, INSERM U1148, France (P.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory G.","family":"Schwartz","sequence":"additional","affiliation":[{"name":"University of Colorado School of Medicine, Aurora (G.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Szarek","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology, SUNY Downstate School of Public Health, Brooklyn, NY (M.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emil","family":"Hagstr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, Cardiology, Uppsala University, Sweden (E.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Badimon","sequence":"additional","affiliation":[{"name":"Cardiovascular Program-ICCC, CiberCV, IR-Hospital de la Santa Creu i Sant Pau, Barcelona, Spain (L.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. John","family":"Chapman","sequence":"additional","affiliation":[{"name":"Endocrinology Metabolism Division, Pitie\u2013Salpetriere University Hospital, Sorbonne University and National Institute for Health and Medical Research (INSERM), Paris, France (M.J.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Boileau","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Paris, INSERM U1148 and Genetics Department, APHP-Hospital Bichat-Claude Bernard, France (C.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotirios","family":"Tsimikas","sequence":"additional","affiliation":[{"name":"Sulpizio Cardiovascular Center, Division of Cardiovascular Medicine, University of California San Diego, La Jolla (S.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry N.","family":"Ginsberg","sequence":"additional","affiliation":[{"name":"Irving Institute for Clinical and Translational Research, Columbia University, New York (H.N.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poulabi","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garen","family":"Manvelian","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pordy","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibylle","family":"Hess","sequence":"additional","affiliation":[{"name":"Sanofi Aventis Deutschland GmbH, Translational Medicine and Early Development, Biomarkers and Clinical Bioanalyses, Frankfurt, Germany (S.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John D.","family":"Overton","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca A.","family":"Lotta","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George D.","family":"Yancopoulos","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goncalo R.","family":"Abecasis","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aris","family":"Baras","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Paulding","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals Inc, Tarrytown, NY (A.D., P.B., G.M., R.P., J.D.O., L.A.L., G.D.Y., G.R.A., A.B., C.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"On behalf of the Regeneron Genetics Center and the ODYSSEY OUTCOMES Investigators","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","unstructured":"Global Health Estimates 2016: Disease Burden by Cause Age Sex by Country and by Region 2000-2016. 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