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However, the applicable target of PCSK9-mAbs remains inconclusive so far. Therefore, this first meta-analysis was carried out to clarify the therapeutic efficacy and safety of PCSK9-mAbs on the potential patients: familial hypercholesterolemia and statin-intolerant patients. All randomized controlled trials that met the search terms were retrieved in multiple databases. Efficacy outcomes included parameter changes from baseline in LDL-C and other lipid levels. Therapeutic safety were evaluated by rates of common adverse events. A total of 15 studies encompassing 4,288 patients with at least 8 weeks duration were selected. Overall, the therapeutic efficacy was achieved with significant reduction in LDL-C, TC, TG, Lp(a), Apo-B versus placebo. The decline in familial hypercholesterolemia patients (\u221253.28%, 95% CI: \u221259.88 to \u221246.68%) was even more obvious than that in statin-intolerant patients (\u221234.95%, 95% CI: \u221241.46 to \u221228.45%). No obvious safety difference was found out in the rates of common and serious adverse events. To conclude, PCSK9-mAb contributes to the decreased level of LDL-C and other lipids in familial hypercholesterolemia and statin-intolerant patients with satisfactory safety and tolerability.<\/jats:p>","DOI":"10.1038\/s41598-017-00316-3","type":"journal-article","created":{"date-parts":[[2017,3,13]],"date-time":"2017-03-13T16:29:06Z","timestamp":1489422546000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Therapeutic efficacy and safety of PCSK9-monoclonal antibodies on familial hypercholesterolemia and statin-intolerant patients: A meta-analysis of 15 randomized controlled trials"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-2065","authenticated-orcid":false,"given":"Li Jun","family":"Qian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan Mei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Chu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,22]]},"reference":[{"key":"316_CR1","unstructured":"Goldstein, J. 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The diabetes dilemma for statin users. NewYork Times. March 4, 2012. http:\/\/www.nytimes.com\/2012\/03\/05\/opinion\/the-diabetes-dilemma-for-statin-users.html. Accessed October 19, 2012."},{"key":"316_CR5","doi-asserted-by":"publisher","first-page":"1670","DOI":"10.1016\/S0140-6736(10)61350-5","volume":"376","author":"C Baigent","year":"2010","unstructured":"Baigent, C. et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet \n                           376, 1670\u201381 (2010).","journal-title":"Lancet"},{"key":"316_CR6","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0140-6736(12)60771-5","volume":"380","author":"EA Stein","year":"2012","unstructured":"Stein, E. A. et al. Effect of a monoclonal antibody to PCSK9, REGN727\/SAR236553, to reduce low-density lipoprotein cholesterol in patients with heterozygous familial hypercholesterolaemia on stable statin dose with or without ezetimibe therapy: a phase 2 randomised controlled trial. Lancet \n                           380, 29\u201336 (2012).","journal-title":"Lancet"},{"key":"316_CR7","doi-asserted-by":"publisher","first-page":"1888","DOI":"10.1016\/j.jacc.2012.08.986","volume":"60","author":"CS Dias","year":"2012","unstructured":"Dias, C. S. et al. Effects of AMG 145 on low-density lipoprotein cholesterol levels: results from 2 randomized, double-blind, placebo-controlled, ascending-dose phase 1 studies in healthy volunteers and hypercholesterolemic subjects on statins. 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Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin\/kexin type 9 in combination with a statin in patients with hypercholesterolaemia (LAPLACE-TIMI 57): a randomised, placebo-controlled, dose-ranging, phase 2 study. Lancet \n                           380, 2007\u20132017 (2012).","journal-title":"Lancet"},{"key":"316_CR12","doi-asserted-by":"publisher","first-page":"2408","DOI":"10.1161\/CIRCULATIONAHA.112.144055","volume":"126","author":"F Raal","year":"2012","unstructured":"Raal, F. et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin\/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the reduction of LDL-C with PCSK9 inhibition in heterozygous familial hypercholesterolemia disorder (RUTHERFORD) randomized trial. 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Effects of evolocumab (AMG 145), a monoclonal antibody to PCSK9, in hypercholesterolemic, statin-treated Japanese patients at high cardiovascular risk\u2014primary results from the phase 2 YUKAWA study. Circ J. \n                           78, 1073\u20131082 (2014).","journal-title":"Circ J."},{"key":"316_CR17","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1056\/NEJMoa1316222","volume":"370","author":"DJ Blom","year":"2014","unstructured":"Blom, D. J. et al. A 52-week placebo-controlled trial of evolocumab in hyperlipidemia. N Engl J Med \n                           370, 1809\u20131819 (2014).","journal-title":"N Engl J Med"},{"key":"316_CR18","doi-asserted-by":"publisher","first-page":"3478","DOI":"10.1093\/eurheartj\/eht273","volume":"34","author":"BG Nordestgaard","year":"2013","unstructured":"Nordestgaard, B. G. et al. 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