OBJECTIVES

As novel lipid lowering therapies (LLTs) beyond statins and ezetimibe are becoming available in the recent years, this study aimed to critically review the contemporary meta-analyses and network meta-analyses (NMAs) measuring the impact of novel LLTs on low-density lipoprotein cholesterol (LDL-C) reduction and other outcomes of interest.

METHODS

A targeted literature review was performed in Embase and MEDLINE from January 2016 until April 2021, to identify meta-analyses and NMAs reporting efficacy of ezetimibe, inclisiran, alirocumab, evolocumab and bempedoic acid. Population of interest were patients with dyslipidaemia, hyperlipidaemia, hypercholesterolaemia treated with LDL-C lowering therapies. Outcomes of interest were: LDL-C reduction, adverse events, other lipid- and inflammation parameters. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used.

RESULTS

The literature search yielded 338 unique records, 118 excluded at title/abstract review and a total 27 articles (22 meta-analyses, 5 NMAs) were selected for data extraction. The meta-analyses were based on as few as three up to 41 studies (comprising 388 to 89,603 patients) and the majority being Phase 2 and/or 3; only one reported using patient level data. The efficacy of ezetimibe, alirocumab, evolocumab, inclisiran, and bempedoic acid, was reported in sixteen, eleven, ten, two and seven studies, respectively. Half of the studies analysed discontinuation rates and adverse events. Heterogeneity for LDL-C as expressed by I2 ranged across studies 0-100%. Consistent with individual clinical trials, the published meta-analyses despite limitations, heterogeneity and bias reported, have demonstrated that LLTs lead to significant LDL-C reductions.

CONCLUSIONS

This contemporary review has summarized and critically appraised the most recent published meta-analyses on LDL-C efficacy using publicly available data for LLTs. A network meta-analysis using the totality of data would help further inform relative efficacy of LLTs.