Network meta‐analysis of randomized trials evaluating the comparative efficacy of lipid‐lowering therapies added to maximally tolerated statins for the reduction of low‐density lipoprotein cholesterol

Toth, P. P., Bray, S., Villa, G., Palagashvili, T., Sattar, N. , Stroes, E. S. G. and Worth, G. M. (2022) Network meta‐analysis of randomized trials evaluating the comparative efficacy of lipid‐lowering therapies added to maximally tolerated statins for the reduction of low‐density lipoprotein cholesterol. Journal of the American Heart Association, 11(18), e025551. (doi: 10.1161/JAHA.122.025551) (PMID:36073669) (PMCID:PMC9683660)

Abstract

Background: Lowering low‐density lipoprotein cholesterol (LDL‐C) levels decreases major cardiovascular events and is recommended for patients at elevated cardiovascular risk. However, appropriate doses of statin therapy are often insufficient to reduce LDL‐C in accordance with current guidelines. In such cases, treatment could be supplemented with nonstatin lipid‐lowering therapy. Methods and Results: A systematic literature review and network meta‐analysis were conducted on randomized controlled trials of nonstatin lipid‐lowering therapy added to maximally tolerated statins, including statin‐intolerant patients. The primary objective was to assess relative efficacy of nonstatin lipid‐lowering therapy in reducing LDL‐C levels at week 12. Secondary objectives included the following: LDL‐C level reduction at week 24 and change in non–high‐density lipoprotein cholesterol and apolipoprotein B at week 12. There were 48 randomized controlled trials included in the primary network meta‐analysis. All nonstatin agents significantly reduced LDL‐C from baseline versus placebo, regardless of background therapy. At week 12, evolocumab, 140 mg every 2 weeks (Q2W)/420 mg once a month, and alirocumab, 150 mg Q2W, were the most efficacious regimens, followed by alirocumab, 75 mg Q2W, alirocumab, 300 mg once a month, inclisiran, bempedoic acid/ezetimibe fixed‐dose combination, and ezetimibe and bempedoic acid used as monotherapies. Primary end point results were generally consistent at week 24, and for other lipid end points at week 12. Conclusions: Evolocumab, 140 mg Q2W/420 mg once a month, and alirocumab, 150 mg Q2W, were consistently the most efficacious nonstatin regimens when added to maximally tolerated statins to lower LDL‐C, non–high‐density lipoprotein cholesterol, and apolipoprotein B levels and facilitate attainment of guideline‐recommended risk‐stratified lipoprotein levels.

• Item Type: Articles
• Additional Information: This systematic review and network meta‐analysis was sponsored by Amgen Inc, as were all trials of evolocumab included in the analysis.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Sattar, Professor Naveed
• Authors: Toth, P. P., Bray, S., Villa, G., Palagashvili, T., Sattar, N., Stroes, E. S. G., and Worth, G. M.
• 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: 08 September 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Journal of the American Heart Association 11(18): e025551
• Publisher Policy: Reproduced under a Creative Commons License