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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
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.
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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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