{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T12:24:47Z","timestamp":1792671887266,"version":"4.5.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2019,3,19]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Lipoprotein(a) [Lp(a)] may play a causal role in atherosclerosis. PCSK9 (proprotein convertase subtilisin\/kexin 9) inhibitors have been shown to significantly reduce plasma Lp(a) concentration. However, the relationship between Lp(a) levels, PCSK9 inhibition, and cardiovascular risk reduction remains undefined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>Lp(a) was measured in 25\u2009096 patients in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), a randomized trial of evolocumab versus placebo in patients with established atherosclerotic cardiovascular disease (median follow-up, 2.2 years). Cox models were used to assess the independent prognostic value of Lp(a) and the efficacy of evolocumab for coronary risk reduction by baseline Lp(a) concentration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The median (interquartile range) baseline Lp(a) concentration was 37 (13\u2013165) nmol\/L. In the placebo arm, patients with baseline Lp(a) in the highest quartile had a higher risk of coronary heart disease death, myocardial infarction, or urgent revascularization (adjusted hazard ratio quartile 4: quartile 1, 1.22; 95% CI, 1.01\u20131.48) independent of low-density lipoprotein cholesterol. At 48 weeks, evolocumab significantly reduced Lp(a) by a median (interquartile range) of 26.9% (6.2%\u201346.7%). The percent change in Lp(a) and low-density lipoprotein cholesterol at 48 weeks in patients taking evolocumab was moderately positively correlated (\n                      <jats:italic>r<\/jats:italic>\n                      =0.37; 95% CI, 0.36\u20130.39;\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). Evolocumab reduced the risk of coronary heart disease death, myocardial infarction, or urgent revascularization by 23% (hazard ratio, 0.77; 95% CI, 0.67\u20130.88) in patients with a baseline Lp(a) &gt;median, and by 7% (hazard ratio, 0.93; 95% CI, 0.80\u20131.08;\n                      <jats:italic>P<\/jats:italic>\n                      interaction=0.07) in those \u2264median. Coupled with the higher baseline risk, the absolute risk reductions, and number needed to treat over 3 years were 2.49% and 40 versus 0.95% and 105, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Higher levels of Lp(a) are associated with an increased risk of cardiovascular events in patients with established cardiovascular disease irrespective of low-density lipoprotein cholesterol. Evolocumab significantly reduced Lp(a) levels, and patients with higher baseline Lp(a) levels experienced greater absolute reductions in Lp(a) and tended to derive greater coronary benefit from PCSK9 inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical Trial Registration:<\/jats:title>\n                    <jats:p>\n                      URL:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n                      . Unique identifier: NCT01764633.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.118.037184","type":"journal-article","created":{"date-parts":[[2019,1,17]],"date-time":"2019-01-17T08:44:06Z","timestamp":1547714646000},"page":"1483-1492","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":911,"title":["Lipoprotein(a), PCSK9 Inhibition, and Cardiovascular Risk"],"prefix":"10.1161","volume":"139","author":[{"given":"Michelle L.","family":"O\u2019Donoghue","sequence":"first","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Fazio","sequence":"additional","affiliation":[{"name":"Center for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health &amp; Science University, Portland (S.F.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert P.","family":"Giugliano","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik S.G.","family":"Stroes","sequence":"additional","affiliation":[{"name":"Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands (E.S.G.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estella","family":"Kanevsky","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Gouni-Berthold","sequence":"additional","affiliation":[{"name":"Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University of Cologne, Germany (I.G.-B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KyungAh","family":"Im","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Lira Pineda","sequence":"additional","affiliation":[{"name":"Amgen, Thousand Oaks, CA (A.L.P., S.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Amgen, Thousand Oaks, CA (A.L.P., S.M.W.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"\u010ce\u0161ka","sequence":"additional","affiliation":[{"name":"Center for Preventive Cardiology, 3rd Internal Medicine Clinic, University General Hospital and Charles University 1st Medical Faculty, Prague, Czech Republic (R.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marat V.","family":"Ezhov","sequence":"additional","affiliation":[{"name":"National Cardiology Research Center, Moscow, Russia (M.V.E.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Wouter","family":"Jukema","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Leiden University Medical Center, The Netherlands (J.W.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik K.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Aarhus University Hospital and Department of Clinical Medicine, Health, Aarhus University, Denmark (H.K.J.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Lale","family":"Tokg\u00f6zo\u011flu","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, Hacettepe University, Ankara, Turkey (S.L.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Mach","sequence":"additional","affiliation":[{"name":"Cardiology Division, University of Geneva, Switzerland (F.M.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Huber","sequence":"additional","affiliation":[{"name":"3rd Department of Medicine, Cardiology and Intensive Care Medicine, Wilhelminenhospital and Sigmund Freud University, Medical Faculty, Vienna, Austria (K.H.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Sever","sequence":"additional","affiliation":[{"name":"Imperial College London, UK (P.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony C.","family":"Keech","sequence":"additional","affiliation":[{"name":"Sydney Medical School, National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Australia (A.C.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terje R.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Oslo University Hospital, Ullev\u00e5l and Medical Faculty, University of Oslo, Norway (T.R.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Cardiovascular Division, Brigham and Women\u2019s Hospital, Boston, MA (M.L.O., R.P.G., E.K., K.A.I., 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