A Comparison of Ezetimibe and Evolocumab for Atherogenic Lipid Reduction in Four Patient Populations: A Pooled Efficacy and Safety Analysis of Three Phase 3 Studies.

Abstract

IntroductionClinicians, payers, guideline committees, and policymakers support the use of high-intensity statins in patients at high risk for complications of cardiovascular disease (CVD). Guidelines and recommendations provide guidance on next steps for patients with inadequate low-density lipoprotein cholesterol (LDL-C) control on maximally tolerated statin or for those who are statin-intolerant. Ezetimibe and evolocumab improve CV outcomes when added to statins in high-CV-risk populations. The aim of the study was to compare evolocumab and ezetimibe for lipid-lowering efficacy and safety.MethodsWe summarized data from 1427 patients from three phase 3 evolocumab studies comparing double-blinded evolocumab vs. ezetimibe. These studies evaluated four distinct populations: those free of CVD receiving each agent as monotherapy, patients with CVD receiving add-on therapy to low- or high-intensity statin, and statin-intolerant patients. Lipid efficacy and safety were reported at week 12.ResultsAcross the studies, evolocumab reduced LDL-C by a mean 55–61% from baseline to week 12; ezetimibe lowered LDL-C by 18–20% from baseline (mean difference = 38–43% favoring evolocumab; p < 0.0001). This corresponded to absolute reductions in LDL-C of 60–104 mg/dL with evolocumab vs. 17–35 mg/dL with ezetimibe. Evolocumab also significantly improved other lipids and led to a higher percentage of patients achieving LDL-C goals vs. ezetimibe. Adverse events and discontinuation rates (oral and parenteral therapy) were balanced across groups, suggesting good tolerance and acceptance of both treatments.ConclusionsEvolocumab outperformed ezetimibe in efficacy and lipid goal attainment. Both products demonstrated good safety/tolerability. These data may help guide access decisions for high-risk patients with inadequate treatment response or intolerance to statin therapy.