{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:02:01Z","timestamp":1768341721303,"version":"3.49.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2017,5,9]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Evolocumab, a fully human monoclonal antibody to PCSK9 (proprotein convertase subtilisin\/kexin type 9), markedly reduces low-density lipoprotein cholesterol across diverse patient populations. The objective of this study was to assess the safety and tolerability of evolocumab in a pooled safety analysis from phase 2 or 3 randomized and placebo or comparator-controlled trials (integrated parent trials) and the first year of open-label extension (OLE) trials that included a standard-of-care control group.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>This analysis included adverse event (AE) data from 6026 patients in 12 phase 2 and 3 parent trials, with a median exposure of 2.8 months, and, of those patients, from 4465 patients who continued with a median follow-up of 11.1 months in 2 OLE trials. AEs were analyzed separately for the parent and OLE trials. Overall AE rates, serious AEs, laboratory assessments, and AEs of interest were evaluated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Overall AE rates were similar between evolocumab and control in the parent trials (51.1% versus 49.6%) and in year 1 of OLE trials (70.0% versus 66.0%), as were those for serious AEs. Elevations of serum transaminases, bilirubin, and creatine kinase were infrequent and similar between groups. Muscle-related AEs were similar between evolocumab and control. Neurocognitive AEs were infrequent and balanced during the double-blind parent studies (5 events [0.1%], evolocumab groups versus 6 events [0.3%], control groups). In the OLE trials, 27 patients (0.9%) in the evolocumab groups and 5 patients (0.3%) in the control groups reported neurocognitive AEs. No neutralizing antievolocumab antibodies were detected.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>Overall, this integrated safety analysis of 6026 patients pooled across phase 2\/3 trials and 4465 patients who continued in OLE trials for 1 year supports a favorable benefit-risk profile for evolocumab.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circulationaha.116.025233","type":"journal-article","created":{"date-parts":[[2017,3,2]],"date-time":"2017-03-02T02:00:20Z","timestamp":1488420020000},"page":"1819-1831","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":69,"title":["Pooled Safety Analysis of Evolocumab in Over 6000 Patients From Double-Blind and Open-Label Extension Studies"],"prefix":"10.1161","volume":"135","author":[{"given":"Peter P.","family":"Toth","sequence":"first","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Descamps","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacques","family":"Genest","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naveed","family":"Sattar","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Preiss","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo","family":"Dent","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Constantine","family":"Djedjos","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuna","family":"Wu","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Geller","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Uhart","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ransi","family":"Somaratne","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott M.","family":"Wasserman","sequence":"additional","affiliation":[{"name":"From CGH Medical Center, Sterling, IL, and Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD (P.P.T.); Lipid Clinic, Centres Hospitaliers Jolimont, Haine-Saint-Paul, Belgium (O.D.); The McGill University Health Centre, Montreal, Canada (J.G.); Institute of Cardiovascular and Medical Sciences, University of Glasgow, UK (N.S.); Medical Research Council Population Health Research Unit, Clinical Trial Service Unit and..."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2016.07.510"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacl.2013.10.001"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehs092"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000437738.63853.7a"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.02.615"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.108.838466"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.115.018381"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702027200"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1316222"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61770-X"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-14-0130"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.03.018"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61771-1"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.144055"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)61399-4"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.4030"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.03.019"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2012.25790"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.113.007012"},{"key":"e_1_3_4_21_2","unstructured":"United States Department of Health and Human Services. 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