Moderate-Intensity Statin Plus Ezetimibe: Time to Rethink it as an Optimal Initial Lipid-Lowering Strategy

Abstract

Achievement of low-density lipoprotein cholesterol (LDL-C) targets is crucial for the prevention of cardiovascular disease (CVD) in individuals with dyslipidaemia who are at high risk. Current guidelines recommend high-intensity statins at the highest tolerated dose as initial treatment to achieve LDL-C goals. However, the real-world situation is dismal: high-intensity statins are underused and achievement of LDL-C goals is suboptimal. Various challenges exist in the implementation of the recommended initial treatment strategy, including hesitancy to use high-intensity statins, non-adherence, and side effects, and the response to high-intensity statins varies across individuals. Emerging studies have shown another line of lipid-lowering, moderate-intensity statins in combination with ezetimibe, presenting considerable efficacy/effectiveness, along with better safety and adherence compared to statin intensification alone. Here we review the clinical evidence, treatment guidelines and challenges associated with high-intensity statins, and summarise the evidence on the combination therapy, moderate-intensity statin plus ezetimibe, which is the core strategy recommended by the 2023 Chinese Guideline for Lipid Management, as a possible primary treatment to achieve the LDL-C targets across several populations. The upfront use of a moderate-intensity statin plus ezetimibe may improve LDL-C control and lead to the prevention of CVD in real-world settings.

Fig. 1

Reasons for moving from upfront use of a high-intensity statin to a moderate-intensity statin plus ezetimibe to achieve the LDL-C goals. CVD cardiovascular disease, LDL-C low-density lipoprotein cholesterol

Fig. 2

Proposed treatment algorithm for LDL-C lowering using pharmacological intervention. CVD cardiovascular disease, LDL-C low-density lipoprotein cholesterol, PCSK9 proprotein convertase subtilisin/kexin type 9