{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:35:49Z","timestamp":1790670949243,"version":"4.1.0"},"reference-count":60,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,12,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">We sought to examine the efficacy and safety of 2 PCSK9 (proprotein convertase subtilisin\/kexin type 9) inhibitors: alirocumab and evolocumab.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      We performed a systematic review and meta\u2010analysis of randomized controlled trials comparing treatment with and without PCSK9 inhibitors; 35 randomized controlled trials comprising 45\u00a0539 patients (mean follow\u2010up: 85.5\u00a0weeks) were included. Mean age was 61.0\u00b12.8\u00a0years, and mean baseline low\u2010density lipoprotein cholesterol was 106\u00b122\u00a0mg\/dL. Compared with no PCSK9 inhibitor therapy, treatment with a PCSK9 inhibitor was associated with a lower rate of myocardial infarction (2.3% versus 3.6%; odds ratio [OR]: 0.72 [95% confidence interval (CI), 0.64\u20130.81];\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001), stroke (1.0% versus 1.4%; OR: 0.80 [95% CI, 0.67\u20130.96];\n                      <jats:italic>P<\/jats:italic>\n                      =0.02), and coronary revascularization (4.2% versus 5.8%; OR: 0.78 [95% CI, 0.71\u20130.86];\n                      <jats:italic>P<\/jats:italic>\n                      &lt;0.001). Overall, no significant change was observed in all\u2010cause mortality (OR: 0.71 [95% CI, 0.47\u20131.09];\n                      <jats:italic>P<\/jats:italic>\n                      =0.12) or cardiovascular mortality (OR: 1.01 [95% CI, 0.85\u20131.19];\n                      <jats:italic>P<\/jats:italic>\n                      =0.95). A significant association was observed between higher baseline low\u2010density lipoprotein cholesterol and benefit in all\u2010cause mortality (\n                      <jats:italic>P<\/jats:italic>\n                      =0.038). No significant change was observed in neurocognitive adverse events (OR: 1.12 [95% CI, 0.88\u20131.42];\n                      <jats:italic>P<\/jats:italic>\n                      =0.37), myalgia (OR: 0.95 [95% CI, 0.75\u20131.20];\n                      <jats:italic>P<\/jats:italic>\n                      =0.65), new onset or worsening of preexisting diabetes mellitus (OR: 1.05 [95% CI, 0.95\u20131.17];\n                      <jats:italic>P<\/jats:italic>\n                      =0.32), and increase in levels of creatine kinase (OR: 0.84 [95% CI, 0.70\u20131.01];\n                      <jats:italic>P<\/jats:italic>\n                      =0.06) or alanine or aspartate aminotransferase (OR: 0.96 [95% CI, 0.82\u20131.12];\n                      <jats:italic>P<\/jats:italic>\n                      =0.61).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Treatment with a PCSK9 inhibitor is well tolerated and improves cardiovascular outcomes. Although no overall benefit was noted in all\u2010cause or cardiovascular mortality, such benefit may be achievable in patients with higher baseline low\u2010density lipoprotein cholesterol.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.117.006910","type":"journal-article","created":{"date-parts":[[2017,12,9]],"date-time":"2017-12-09T20:10:21Z","timestamp":1512850221000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":176,"title":["Effect of PCSK9 Inhibitors on Clinical Outcomes in Patients With Hypercholesterolemia: A Meta\u2010Analysis of 35 Randomized Controlled Trials"],"prefix":"10.1161","volume":"6","author":[{"given":"Aris","family":"Karatasakis","sequence":"first","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"},{"name":"Rutgers New Jersey Medical School, Newark, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A","family":"Danek","sequence":"additional","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"},{"name":"Rutgers New Jersey Medical School, Newark, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"Karacsonyi","sequence":"additional","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bavana V","family":"Rangan","sequence":"additional","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele K","family":"Roesle","sequence":"additional","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Knickelbine","sequence":"additional","affiliation":[{"name":"Minneapolis Heart Institute, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Miedema","sequence":"additional","affiliation":[{"name":"Minneapolis Heart Institute, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Houman","family":"Khalili","sequence":"additional","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahid","family":"Ahmad","sequence":"additional","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuaib","family":"Abdullah","sequence":"additional","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhash","family":"Banerjee","sequence":"additional","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanouil S.","family":"Brilakis","sequence":"additional","affiliation":[{"name":"VA North Texas Health Care System and University of Texas Southwestern Medical Center, Dallas, TX"},{"name":"Minneapolis Heart Institute, Minneapolis, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-005-5686-z"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.001800"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.088591"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1410489"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1615664"},{"key":"e_1_3_3_7_2","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0","author":"Higgins JPT","year":"2011","unstructured":"Higgins JPT, Green S, eds. 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