Ezetimibe in high-risk, previously treated statin patients: a systematic review and network meta-analysis of lipid efficacy

Purpose: While statins are used as first-line treatments for high-risk patients with hypercholesterolemia, statin monotherapy is often insufficient to achieve target low-density lipoprotein cholesterol (LDL-C) levels. Second-line treatment options include up-titration of statin dose, switching to a more potent statin, or combination therapy, e.g., with ezetimibe. The aim of this study was to evaluate the efficacy of adding ezetimibe to simvastatin, atorvastatin, or rosuvastatin monotherapy versus doubling the dosage or switching to a higher-potency statin in a population of patients with hypocholesterolemia at high risk of cardiovascular disease (CVD) and who had been previously treated with a statin.

Methods: A systematic literature search was performed and evidence bases were established for populations of atorvastatin-, simvastatin-, and rosuvastatin-experienced patients using eligible randomized controlled trials (RCTs). Based on the available data, we constructed networks of evidence and conducted a Bayesian network meta-analysis (NMA) within each statin population. The primary outcome of interest was percent change from baseline in LDL-C. Changes in total cholesterol were explored as a secondary outcome.

Findings: Across all patient populations, 35 RCTs were identified and included in the evidence base. Among patients on simvastatin therapy, the addition of ezetimibe resulted in a mean difference (MD) in LDL-C of - 13.62% (95% CrI - 19.99, - 6.91; see table below) compared to doubling the starting dose of simvastatin. In the population of patients on atorvastatin therapy, the addition of ezetimibe resulted in an MD in LDL-C of - 14.71% (95% CrI - 16.46, - 12.95) compared to doubling the starting dose of atorvastatin. The addition of ezetimibe to rosuvastatin resulted in an MD in LDL-C of - 14.96% (95% CrI - 17.79, - 12.11), compared to doubling the starting rosuvastatin dose. Similar trends were observed for changes in total cholesterol.

Implications: Given the available data, the addition of ezetimibe to ongoing simvastatin, atorvastatin, or rosuvastatin monotherapy offers greater reduction in LDL-C among patients at high risk of CVD compared to doubling the initial statin dose.