{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T12:33:59Z","timestamp":1792154039149,"version":"4.4.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Stroke"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Purpose\u2014<\/jats:title>\n                    <jats:p>The PCSK9 (proprotein convertase subtilisin-kexin type 9) monoclonal antibody evolocumab lowered LDL (low-density lipoprotein) cholesterol by 59% to 0.8 (0.5\u20131.2) mmol\/L and significantly reduced major vascular events in the FOURIER trial (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk). Herein, we report the results of a prespecified analysis of cerebrovascular events in the overall trial population and in patients stratified by prior stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods\u2014<\/jats:title>\n                    <jats:p>FOURIER was a randomized, double-blind trial comparing evolocumab versus placebo in patients with established atherosclerosis, additional risk factors, and LDL cholesterol levels \u22651.8 (or non-HDL [high-density lipoprotein] \u22652.6 mmol\/L) on statin therapy. The median follow-up was 2.2 years. We analyzed the efficacy of evolocumab to reduce overall stroke and stroke subtypes, as well as the primary cardiovascular composite end point by subgroups according to a history of stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results\u2014<\/jats:title>\n                    <jats:p>\n                      Among the 27 564 patients, 469 (1.7%) experienced a total of 503 strokes of which 421 (84%) were ischemic. Prior ischemic stroke, diabetes mellitus, elevated CRP (C-reactive protein), history of heart failure, older age, nonwhite race, peripheral arterial disease, and renal insufficiency were independent predictors of stroke. Evolocumab significantly reduced all stroke (1.5% versus 1.9%; hazard ratio, 0.79 [95% CI, 0.66\u20130.95];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.01) and ischemic stroke (1.2% versus 1.6%; hazard ratio, 0.75 [95% CI, 0.62\u20130.92];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.005), with no difference in hemorrhagic stroke (0.21% versus 0.18%; hazard ratio, 1.16 [95% CI, 0.68\u20131.98];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.59). These findings were consistent across subgroups, including among the 5337 patients (19%) with prior ischemic stroke in whom the hazard ratios (95% CIs) were 0.85 (0.72\u20131.00) for the cardiovascular composite, 0.90 (0.68\u20131.19) for all stroke, and 0.92 (0.68\u20131.25) for ischemic stroke (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      interactions, 0.91, 0.22, and 0.09, respectively, compared with patients without a prior ischemic stroke).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>Inhibition of PCSK9 with evolocumab added to statin in patients with established atherosclerosis reduced ischemic stroke and cardiovascular events in the total population and in key subgroups, including those with prior ischemic stroke.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration\u2014<\/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\/strokeaha.119.027759","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T05:00:55Z","timestamp":1587445255000},"page":"1546-1554","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":180,"title":["Stroke Prevention With the PCSK9 (Proprotein Convertase Subtilisin-Kexin Type 9) Inhibitor Evolocumab Added to Statin in High-Risk Patients With Stable Atherosclerosis"],"prefix":"10.1161","volume":"51","author":[{"given":"Robert P.","family":"Giugliano","sequence":"first","affiliation":[{"name":"From the TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (R.P.G., E.A.B., S.A.M., M.S.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terje R.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"Oslo Universitetssykehus HF, Endocrinology\u2013Morbid Obesity and Preventive Medicine, Norway (T.R.P.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Saver","sequence":"additional","affiliation":[{"name":"Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine at UCLA, Los Angeles, CA (J.L.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"Sever","sequence":"additional","affiliation":[{"name":"National Heart and Lung Institute, Imperial College London, United Kingdom (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, Australia (A.C.K.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin A.","family":"Bohula","sequence":"additional","affiliation":[{"name":"From the TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (R.P.G., E.A.B., S.A.M., M.S.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"From the TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (R.P.G., E.A.B., S.A.M., M.S.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"Amgen, Inc, Global Development, Thousand Oaks, CA (S.M.W., N.H., H.W., A.L.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narimon","family":"Honarpour","sequence":"additional","affiliation":[{"name":"Amgen, Inc, Global Development, Thousand Oaks, CA (S.M.W., N.H., H.W., A.L.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei","family":"Wang","sequence":"additional","affiliation":[{"name":"Amgen, Inc, Global Development, Thousand Oaks, CA (S.M.W., N.H., H.W., A.L.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Lira Pineda","sequence":"additional","affiliation":[{"name":"Amgen, Inc, Global Development, Thousand Oaks, CA (S.M.W., N.H., H.W., A.L.P.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc S.","family":"Sabatine","sequence":"additional","affiliation":[{"name":"From the TIMI (Thrombolysis in Myocardial Infarction) Study Group, Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (R.P.G., E.A.B., S.A.M., M.S.S.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the FOURIER 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