{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:16:01Z","timestamp":1788362161458,"version":"build-2803163510"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"abstract":"\n BACKGROUND:<\/jats:title>\n Evolocumab, a PCSK9 (proprotein convertase subtilisin\u2013kexin type 9) inhibitor, significantly reduced the risk of cardiovascular events in patients without previous myocardial infarction or stroke in the VESALIUS-CV trial (Effect of Evolocumab in Patients at High Cardiovascular Risk without Prior Myocardial Infarction or Stroke). However, mortality results have yet to be fully characterized.<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n VESALIUS-CV was a double-blind study of 12 257 patients (median age, 66 years [interquartile range, 60\u201371]; 43% women) with qualifying atherosclerosis or high-risk diabetes without previous myocardial infarction or stroke, and low-density lipoprotein-cholesterol \u226590 mg\/dL (or non\u2013high-density lipoprotein-C \u2265120 mg\/dL or apolipoprotein B \u226580 mg\/dL) who were randomized to evolocumab or placebo. Prespecified mortality outcomes of interest included all-cause mortality, subtypes of death (including cardiovascular [CV] and non-CV), and timing of events. Non-CV mortality was further investigated using multistate modeling to assess the contribution of prevention of nonfatal CV events (myocardial infarction, ischemic stroke, and ischemia-driven arterial revascularization) to non-CV mortality.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n Over a median of 4.6 years (interquartile range, 4.0-5.2), 973 (7.9%) patients died: 351 (36%) of CV causes, 497 (51%) of non-CV causes, and 125 (13%) of undetermined cause. All-cause mortality rates were 20% lower with evolocumab compared with placebo: 434 deaths (5-year Kaplan-Meier rate of 7.9%) with evolocumab versus 539 deaths (9.7%) with placebo (hazard ratio, 0.80, 95% CI, 0.70\u20130.91;\n P<\/jats:italic>\n =0.0005). There was consistency of benefit for CV death (156 deaths [2.8%] versus 195 [3.6%]; hazard ratio, 0.79; 95% CI, 0.64\u20130.98), non-CV death (229 [4.2%] versus 268 [5.0%]; hazard ratio, 0.85; 95% CI, 0.71\u20131.01), and deaths of undetermined cause (49 [1.1%] versus 76 [1.4%]; hazard ratio, 0.64; 95% CI, 0.45\u20130.92). Results were consistent regardless of age, sex, region, race, qualifying atherosclerosis or high-risk diabetes, baseline low-density lipoprotein-cholesterol, or background lipid therapy. Postrandomization nonfatal myocardial infarction, ischemic stroke, and ischemia-driven arterial revascularization were associated with increased risk of subsequent non-CV death within the next 4 years, with the majority occurring during the first year after the event. Multistate modeling suggested the observations regarding non-CV death with evolocumab was largely (78%; bootstrap interquartile range, 71\u201392%) driven by the prevention of antecedent nonfatal CV events.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n These results support using evolocumab to improve survival in high-risk patients who have not experienced a previous myocardial infarction or stroke, including those with high-risk diabetes without qualifying atherosclerosis with low-density lipoprotein-cholesterol \u2265 90 mg\/dl (or non-high-density lipoprotein-cholesterol \u2265 120 mg\/dl or apolipoprotein B \u2265 80 mg\/dl).<\/jats:p>\n <\/jats:sec>\n \n REGISTRATION:<\/jats:title>\n \n URL:\n https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n ; Unique identifier: NCT03872401.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/circulationaha.126.082436","type":"journal-article","created":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T07:16:04Z","timestamp":1788160564000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Evolocumab on Mortality Outcomes in Patients Without Previous Myocardial Infarction or Stroke: A Prespecified Analysis of the VESALIUS-CV Randomized Clinical Trial"],"prefix":"10.1161","clinical-trial-number":[{"clinical-trial-number":"nct03872401","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-7675","authenticated-orcid":true,"given":"Robert P.","family":"Giugliano","sequence":"first","affiliation":[{"name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (R.P.G., E.A.B., A.B., S.A.M., M.S.S.)."}],"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 (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (R.P.G., E.A.B., A.B., S.A.M., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4988-4532","authenticated-orcid":true,"given":"Andrea","family":"Bellavia","sequence":"additional","affiliation":[{"name":"Thrombolysis in Myocardial Infarction (TIMI) Study Group, Division of Cardiovascular Medicine, Brigham and Women\u2019s Hospital, Boston, MA (R.P.G., E.A.B., A.B., S.A.M., M.S.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4940-0876","authenticated-orcid":true,"given":"Gaetano M.","family":"De Ferrari","sequence":"additional","affiliation":[{"name":"Cardiology Division, Department of Medical Sciences, University of Turin and Azienda Ospedaliero\u2013Universitaria Citt\u00e0 della Salute e della Scienza, Turin, Italy (G.M.DF.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1040-6229","authenticated-orcid":true,"given":"Lawrence A.","family":"Leiter","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, St. Michael\u2019s Hospital, University of Toronto, Toronto, Canada (L.A.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9680-3689","authenticated-orcid":true,"given":"Jose C.","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Instituto do Coracao, Hospital das Clinicas da Faculdade de Medicina da Universidade de S\u00e3o Paulo, Universidade de S\u00e3o Paulo, S\u00e3o Paulo, Brazil 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