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

Michael J Koren, Peter H Jones, Jennifer G Robinson, David Sullivan, Leslie Cho, Thomas Hucko, J Antonio G Lopez, Alex N Fleishman, Ransi Somaratne, Erik Stroes, Michael J Koren, Peter H Jones, Jennifer G Robinson, David Sullivan, Leslie Cho, Thomas Hucko, J Antonio G Lopez, Alex N Fleishman, Ransi Somaratne, Erik Stroes

Abstract

Introduction: Clinicians, 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.

Methods: We 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.

Results: Across 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.

Conclusions: Evolocumab 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.

Keywords: Dyslipidemia; Evolocumab; Ezetimibe; Lipid-lowering therapy; PCSK9 inhibition.

Figures

Fig. 1
Fig. 1
Baseline and week 12 achieved LDL-C. When calculated LDL-C was  400 mg/dL, ultracentrifugation-determined LDL-C replaced calculated LDL-C from the same blood sample, if available. Diamond indicates mean; center line, median; top and bottom of box, 1st and 3rd quartiles; ends of whiskers, 5th and 95th percentiles. LDL-C low-density lipoprotein cholesterol
Fig. 2
Fig. 2
Percentage of patients achieving LDL-C ≤ 70 mg/dL by baseline LDL-C. When calculated LDL-C was  400 mg/dL, ultracentrifugation-determined LDL-C replaced calculated LDL-C from the same blood sample, if available. LDL-C low-density lipoprotein cholesterol

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