{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T01:48:49Z","timestamp":1792633729938,"version":"4.5.0"},"reference-count":26,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2022,10,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>In FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk), the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab reduced low-density lipoprotein cholesterol (LDL-C) and risk of cardiovascular events and was safe and well tolerated over a median of 2.2 years of follow-up. However, large-scale, long-term data are lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The parent FOURIER trial randomized 27\u2009564 patients with atherosclerotic cardiovascular disease and LDL-C \u226570 mg\/dL on statin to evolocumab versus placebo. Patients completing FOURIER at participating sites were eligible to receive evolocumab in 2 open-label extension studies (FOURIER-OLE [FOURIER Open-Label Extension]) in the United States and Europe; primary analyses were pooled across studies. The primary end point was the incidence of adverse events. Lipid values and major adverse cardiovascular events were prospectively collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      A total of 6635 patients were enrolled in FOURIER-OLE (3355 randomized to evolocumab and 3280 to placebo in the parent study). Median follow-up in FOURIER-OLE was 5.0 years; maximum exposure to evolocumab in parent plus FOURIER-OLE was 8.4 years. At 12 weeks in FOURIER-OLE, median LDL-C was 30 mg\/dL, and 63.2% of patients achieved LDL-C &lt;40 mg\/dL on evolocumab. Incidences of serious adverse events, muscle-related events, new-onset diabetes, hemorrhagic stroke, and neurocognitive events with evolocumab long term did not exceed those for placebo-treated patients during the parent study and did not increase over time. During the FOURIER-OLE follow-up period, patients originally randomized in the parent trial to evolocumab versus placebo had a 15% lower risk of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina or coronary revascularization (hazard ratio, 0.85 [95% CI, 0.75\u20130.96];\n                      <jats:italic>P<\/jats:italic>\n                      =0.008); a 20% lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80 [95% CI, 0.68\u20130.93];\n                      <jats:italic>P<\/jats:italic>\n                      =0.003); and a 23% lower risk of cardiovascular death (hazard ratio, 0.77 [95% CI, 0.60\u20130.99];\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>Long-term LDL-C lowering with evolocumab was associated with persistently low rates of adverse events for &gt;8 years that did not exceed those observed in the original placebo arm during the parent study and led to further reductions in cardiovascular events compared with delayed treatment initiation.<\/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 identifiers: NCT02867813 and NCT03080935.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.122.061620","type":"journal-article","created":{"date-parts":[[2022,8,29]],"date-time":"2022-08-29T03:06:09Z","timestamp":1661742369000},"page":"1109-1119","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":398,"title":["Long-Term Evolocumab in Patients With Established Atherosclerotic Cardiovascular Disease"],"prefix":"10.1161","volume":"146","clinical-trial-number":[{"clinical-trial-number":"nct02867813","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03080935","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8663-0067","authenticated-orcid":true,"given":"Michelle L.","family":"O\u2019Donoghue","sequence":"first","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (M.L.O., R.P.G., S.D.W., J.F.K., K.I., S.A.M., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-7675","authenticated-orcid":true,"given":"Robert P.","family":"Giugliano","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (M.L.O., R.P.G., S.D.W., J.F.K., K.I., S.A.M., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4922-9880","authenticated-orcid":true,"given":"Stephen D.","family":"Wiviott","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (M.L.O., R.P.G., S.D.W., J.F.K., K.I., S.A.M., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}]},{"given":"Anthony","family":"Keech","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (M.L.O., R.P.G., S.D.W., J.F.K., K.I., S.A.M., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia F.","family":"Kuder","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (M.L.O., R.P.G., S.D.W., J.F.K., K.I., S.A.M., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"KyungAh","family":"Im","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (M.L.O., R.P.G., S.D.W., J.F.K., K.I., S.A.M., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabina A.","family":"Murphy","sequence":"additional","affiliation":[{"name":"TIMI Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA (M.L.O., R.P.G., S.D.W., J.F.K., K.I., S.A.M., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose H.","family":"Flores-Arredondo","sequence":"additional","affiliation":[{"name":"Global Development, Amgen, Thousand Oaks, CA (J.H.F.-A., J.A.G.L., B.W., M.L.M., S.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8604-5549","authenticated-orcid":true,"given":"J. 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