{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T02:39:08Z","timestamp":1790995148547,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","funder":[{"name":"Amgen","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}]}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,1,13]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Patients with previous ischemic stroke are at high risk for recurrent stroke and other major adverse cardiovascular events. The benefits of achieving very low levels of low-density lipoprotein cholesterol (LDL-C) in such patients is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We analyzed patients with previous ischemic stroke enrolled in FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), a randomized placebo-controlled trial studying evolocumab in patients with stable atherosclerotic cardiovascular disease (median follow-up, 2.2 years), and through the open-label extension (FOURIER-OLE) period (additional median follow-up, 5 years), to examine the relationship between achieved LDL-C and the long-term incidence of the primary end point (cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization) and stroke-related end points.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>\n                      The analysis included 5291 patients with previous ischemic stroke (&gt;4 weeks). Of these, 666 (12.6%), 1410 (26.6%), 586 (11.1%), 508 (9.6%), and 2121 (40.1%) patients achieved LDL-C values of &lt;20, 20 to &lt;40, 40 to &lt;55, 55 to &lt;70, and \u226570 mg\/dL, respectively. The incidence of the primary end point, all stroke, and ischemic stroke each decreased in a monotonic fashion with lower achieved LDL-C levels on a continuous scale (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>trend<\/jats:sub>\n                      &lt;0.001, 0.002, and 0.002, respectively). Compared with patients with LDL-C \u226570 mg\/dL, those who achieved levels &lt;40 mg\/dL had incidence rate ratios of 0.69 (95% CI, 0.57\u20130.84), 0.73 (95% CI, 0.53\u20130.99), and 0.75 (95% CI, 0.54\u20131.05) for the outcomes of the primary end point, all stroke, and ischemic stroke, respectively. Hemorrhagic strokes were infrequent and unrelated to achieved LDL-C (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      <jats:sub>trend<\/jats:sub>\n                      =0.85).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>In patients with previous ischemic stroke, it appeared that the lower the LDL-C, down to levels &lt;40 mg\/dL, the lower the risk of major adverse cardiovascular events, including recurrent stroke, without a clear increase in risk of hemorrhagic stroke. These findings support the concept that more intensive LDL-C lowering in patients with previous ischemic stroke may be warranted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>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\/NCT01764633.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.125.077549","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T10:01:09Z","timestamp":1762164069000},"page":"86-93","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Efficacy and Safety of Very Low Achieved LDL Cholesterol in Patients With Previous Ischemic Stroke"],"prefix":"10.1161","volume":"153","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3387-7092","authenticated-orcid":true,"given":"Victorien","family":"Monguillon","sequence":"first","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (V.M., M.L.O., J.-G.P., E.A.B., M.S.S., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4772-6565","authenticated-orcid":true,"given":"Peter J.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Mater Misericordiae University Hospital, Dublin, Ireland (P.J.K.)."},{"name":"School of Medicine, University College Dublin, Ireland (P.J.K.)."},{"name":"Health Research Board Stroke Clinical Trials Network Ireland, Dublin (P.J.K.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8663-0067","authenticated-orcid":true,"given":"Michelle L.","family":"O\u2019Donoghue","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (V.M., M.L.O., J.-G.P., E.A.B., M.S.S., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4615-1747","authenticated-orcid":true,"given":"Jeong-Gun","family":"Park","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (V.M., M.L.O., J.-G.P., E.A.B., M.S.S., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5559-8172","authenticated-orcid":true,"given":"Erin A.","family":"Bohula","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (V.M., M.L.O., J.-G.P., E.A.B., M.S.S., R.P.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9141-2251","authenticated-orcid":true,"given":"Jeffrey L.","family":"Saver","sequence":"additional","affiliation":[{"name":"Department of Neurology and Comprehensive Stroke Center, David Geffen School of Medicine, University of California-Los Angeles (J.L.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1513-8793","authenticated-orcid":true,"given":"Dan","family":"Atar","sequence":"additional","affiliation":[{"name":"Department of Cardiology, Oslo University Hospital Ulleval, Norway (D.A.)."},{"name":"Institute of Clinical Medicine, University of Oslo, Norway (D.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9426-9136","authenticated-orcid":true,"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0421-2409","authenticated-orcid":true,"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":"Huei","family":"Wang","sequence":"additional","affiliation":[{"name":"Global Development, Amgen, Thousand Oaks, CA (H.W., 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