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Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia
BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low‐density lipoprotein cholesterol (LDL‐C) when added to statin therapy in patients who need additional LDL‐C reduction. METHODS AND RESULTS: We conducted a systematic rev...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721820/ https://www.ncbi.nlm.nih.gov/pubmed/28971955 http://dx.doi.org/10.1161/JAHA.116.005367 |
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author | Toth, Peter P. Worthy, Gillian Gandra, Shravanthi R. Sattar, Naveed Bray, Sarah Cheng, Lung‐I. Bridges, Ian Worth, Gavin M. Dent, Ricardo Forbes, Carol A. Deshpande, Sohan Ross, Janine Kleijnen, Jos Stroes, Erik S. G. |
author_facet | Toth, Peter P. Worthy, Gillian Gandra, Shravanthi R. Sattar, Naveed Bray, Sarah Cheng, Lung‐I. Bridges, Ian Worth, Gavin M. Dent, Ricardo Forbes, Carol A. Deshpande, Sohan Ross, Janine Kleijnen, Jos Stroes, Erik S. G. |
author_sort | Toth, Peter P. |
collection | PubMed |
description | BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low‐density lipoprotein cholesterol (LDL‐C) when added to statin therapy in patients who need additional LDL‐C reduction. METHODS AND RESULTS: We conducted a systematic review and network meta‐analysis of randomized trials of lipid‐lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid‐lowering therapies that enrolled patients requiring further LDL‐C reduction while on maximally tolerated medium‐ or high‐intensity statin, of which 15 could be relevant for inclusion in LDL‐C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL‐C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (−74.1%; 95% credible interval −79.81% to −68.58%), alirocumab 75 mg (−20.03%; 95% credible interval −27.32% to −12.96%), and alirocumab 150 mg (−13.63%; 95% credible interval −22.43% to −5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe. CONCLUSIONS: PCSK9 inhibitors added to medium‐ to high‐intensity statin therapy significantly reduce LDL‐C in patients requiring further LDL‐C reduction. The network meta‐analysis showed a significant treatment difference in LDL‐C reduction for evolocumab versus alirocumab. |
format | Online Article Text |
id | pubmed-5721820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57218202017-12-12 Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia Toth, Peter P. Worthy, Gillian Gandra, Shravanthi R. Sattar, Naveed Bray, Sarah Cheng, Lung‐I. Bridges, Ian Worth, Gavin M. Dent, Ricardo Forbes, Carol A. Deshpande, Sohan Ross, Janine Kleijnen, Jos Stroes, Erik S. G. J Am Heart Assoc Systematic Review and Meta‐Analysis BACKGROUND: The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors evolocumab and alirocumab substantially reduce low‐density lipoprotein cholesterol (LDL‐C) when added to statin therapy in patients who need additional LDL‐C reduction. METHODS AND RESULTS: We conducted a systematic review and network meta‐analysis of randomized trials of lipid‐lowering therapies from database inception through August 2016 (45 058 records retrieved). We found 69 trials of lipid‐lowering therapies that enrolled patients requiring further LDL‐C reduction while on maximally tolerated medium‐ or high‐intensity statin, of which 15 could be relevant for inclusion in LDL‐C reduction networks with evolocumab, alirocumab, ezetimibe, and placebo as treatment arms. PCSK9 inhibitors significantly reduced LDL‐C by 54% to 74% versus placebo and 26% to 46% versus ezetimibe. There were significant treatment differences for evolocumab 140 mg every 2 weeks at the mean of weeks 10 and 12 versus placebo (−74.1%; 95% credible interval −79.81% to −68.58%), alirocumab 75 mg (−20.03%; 95% credible interval −27.32% to −12.96%), and alirocumab 150 mg (−13.63%; 95% credible interval −22.43% to −5.33%) at ≥12 weeks. Treatment differences were similar in direction and magnitude for PCSK9 inhibitor monthly dosing. Adverse events were similar between PCSK9 inhibitors and control. Rates of adverse events were similar between PCSK9 inhibitors versus placebo or ezetimibe. CONCLUSIONS: PCSK9 inhibitors added to medium‐ to high‐intensity statin therapy significantly reduce LDL‐C in patients requiring further LDL‐C reduction. The network meta‐analysis showed a significant treatment difference in LDL‐C reduction for evolocumab versus alirocumab. John Wiley and Sons Inc. 2017-10-02 /pmc/articles/PMC5721820/ /pubmed/28971955 http://dx.doi.org/10.1161/JAHA.116.005367 Text en © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Systematic Review and Meta‐Analysis Toth, Peter P. Worthy, Gillian Gandra, Shravanthi R. Sattar, Naveed Bray, Sarah Cheng, Lung‐I. Bridges, Ian Worth, Gavin M. Dent, Ricardo Forbes, Carol A. Deshpande, Sohan Ross, Janine Kleijnen, Jos Stroes, Erik S. G. Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia |
title | Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia |
title_full | Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia |
title_fullStr | Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia |
title_full_unstemmed | Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia |
title_short | Systematic Review and Network Meta‐Analysis on the Efficacy of Evolocumab and Other Therapies for the Management of Lipid Levels in Hyperlipidemia |
title_sort | systematic review and network meta‐analysis on the efficacy of evolocumab and other therapies for the management of lipid levels in hyperlipidemia |
topic | Systematic Review and Meta‐Analysis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5721820/ https://www.ncbi.nlm.nih.gov/pubmed/28971955 http://dx.doi.org/10.1161/JAHA.116.005367 |
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