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. 2025 May 13.
doi: 10.1097/FJC.0000000000001712. Online ahead of print.

Comparative Efficacy of Non-Statin Lipid-Lowering Therapies in Patients With Hypercholesterolemia at Increased Cardiovascular Risk: An Updated Network Meta-Analysis

Heather Burnett  1 , Allie Cichewicz  2 , Harshul Natani  3 , Debajyoti Bhowmik  3 , Katharina Buesch  4 , Kyle Fahrbach  2 , Andreas Reichelt  5 , Binod Neupane  1 , Vicki Pierre  1 , Ramandeep Jindal  5
Affiliations

Comparative Efficacy of Non-Statin Lipid-Lowering Therapies in Patients With Hypercholesterolemia at Increased Cardiovascular Risk: An Updated Network Meta-Analysis

Heather Burnett et al. J Cardiovasc Pharmacol. .

Abstract

Hypercholesterolemia is associated with atherosclerotic cardiovascular disease (ASCVD), a leading cause of morbidity and mortality. Non-statin lipid-lowering therapies (LLTs) such as ezetimibe, proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibodies (mAbs), bempedoic acid, and inclisiran have been recommended in clinical guidelines to treat patients with ASCVD and/or high cardiovascular (CV) risk having elevated low-density lipoprotein cholesterol (LDL-C) despite being treated with maximally tolerated doses (MTD) of statins. Our previously published network meta-analysis (NMA)1 was updated in this study to evaluate comparative efficacy of non-statin LLTs in reducing LDL-C among patients with ASCVD and/or high CV risk receiving MTD statins. The systematic literature review previously conducted to inform our NMA was updated through January 2023, wherein more recent clinical trials of non-statin LLTs (ORION-15, ORION-18, HUA TUO) and additional data on monthly dosing regimens for PCSK9 mAbs were included. The outcome of interest was percentage change in LDL-C at week 24. Random-effects Bayesian NMA was performed. Comparative efficacy was estimated as mean difference (MD) with 95% credible interval (CrI). A total of 20 trials were deemed relevant for the NMA. Consistent with the previous findings from our NMA, this study demonstrated that inclisiran provided superior efficacy in LDL-C lowering compared with ezetimibe and bempedoic acid (MD: -44.24 [95% CrI: -51.84, -36.70]). This NMA further reaffirmed that inclisiran provided comparable LDL-C reduction vs. alirocumab (MD: -1.93% [95% CrI: -8.56, 4.20]) and evolocumab (MD: 2.00% [95% CrI: -4.58, 8.60]) among patients with ASCVD and/or high CV risk on MTD statins.

Keywords: ASCVD; Atherosclerosis; LDL-C; indirect treatment comparison.

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Conflict of interest statement

Conflict of interest: Burnett H., Cichewicz A., Fahrbach K., Neupane B., and Pierre V. A are employees of Evidera, a ThermoFisher Company which provides consulting and other research services to life science companies. In their salaried positions, they work with a variety of companies and are precluded from receiving payment or honoraria directly from these organizations for services rendered. Evidera received payment from Novartis for the conduct of this study. Natani H., Reichelt A., and Jindal R. are employees of Novartis. Bhowmik D. was an employee of Novartis at the time of conduct of this study. Katharina Buesch is the Founder and Managing Director of KJM Büsch Consulting and was an external consultant of Novartis at the time of conduct of this study.

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