Systematic review and network meta-analysis on the efficacy of evolocumab and other therapies for the management of lipid levels in hyperlipidemia

Toth, P. P. et al. (2017) Systematic review and network meta-analysis on the efficacy of evolocumab and other therapies for the management of lipid levels in hyperlipidemia. Journal of the American Heart Association, 6(10), e005367. (doi: 10.1161/JAHA.116.005367) (PMID:28971955)

Abstract

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.

• Item Type: Articles
• Additional Information: Amgen sponsored the systematic review and network metaanalysis, which was conducted by Kleijnen Systematic Reviews, Ltd under contract to Amgen. This systematic review and network meta-analysis was sponsored by Amgen Inc, as were all studies of evolocumab included in the analysis
• Keywords: Alirocumab, evidence‐based medicine, evolocumab, ezetimibe, lipids, low‐density lipoprotein cholesterol, meta‐analysis, proprotein convertase subtilisin/kexin type 9 inhibitor, statin therapy.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Toth, P. P., Worthy, G., Gandra, S. R., Sattar, N., Bray, S., Cheng, L.-I., Bridges, I., Worth, G. M., Dent, R., Forbes, C. A., Deshpande, S., Ross, J., Kleijnen, J., and Stroes, E. S.G.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: Journal of the American Heart Association
• Publisher: American Heart Association
• ISSN: 2047-9980
• ISSN (Online): 2047-9980
• Published Online: 02 October 2017
• Copyright Holders: Copyright © 2017 The Authors
• First Published: First published in Journal of the American Heart Association 6(10): e005367
• Publisher Policy: Reproduced under a Creative Commons License