Evolocumab vs. Ezetimibe in Statin-Intolerant Hyperlipidemic Japanese Patients: Phase 3 GAUSS-4 Trial

J Atheroscler Thromb. 2020 May 1;27(5):471-484. doi: 10.5551/jat.50963. Epub 2019 Nov 21.

Abstract

Aim: In patients with hyperlipidemia, intolerance to statins presents a challenge in reducing the risk of events associated with cardiovascular disease. This phase 3, randomized, double-blind trial in Japanese patients with statin intolerance aimed to evaluate the efficacy and safety of evolocumab vs. ezetimibe in lowering low-density lipoprotein-cholesterol (LDL-C).

Methods: This study was conducted in a 12-week, double-blind period followed by an open-label extension designed to characterize 1 year of evolocumab treatment. Statin intolerance was defined as failure of two or more statins due to myalgia, myositis, or rhabdomyolysis. Eligible patients were randomized at 2:2:1:1 into four groups: 420 mg evolocumab every 4 weeks (Q4W)+oral placebo daily, 140 mg evolocumab every 2 weeks (Q2W)+oral placebo daily, subcutaneous (SC) placebo Q4W+10 mg ezetimibe daily, and SC placebo Q2W+ 10 mg ezetimibe daily.

Results: Sixty-one patients were randomized to evolocumab (n=40) or ezetimibe (n=21). For the co-primary endpoints of percent change from the baseline in mean LDL-C to the mean of weeks 10 and 12 and to week 12, the evolocumab-ezetimibe treatment differences were -39.4% (95% CI, -47.2% to -31.5%) and -40.1% (95% CI, -48.7% to -31.6%), respectively (adjusted p<0.0001). The most common adverse events were diarrhea (9.5%) and nasopharyngitis (12.5%) in the ezetimibe and evolocumab groups, respectively, during the double-blind period and nasopharyngitis (29%) during the open-label extension.

Conclusion: Evolocumab was superior to ezetimibe in reducing LDL-C during the 12-week double-blind period in this population of Japanese patients with statin intolerance, with efficacy and safety results maintained for 1 year.

Trial registration: ClinicalTrials.gov, NCT02634580.

Keywords: Cardiovascular disease; PCSK9 inhibitor; Statin intolerance.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Antibodies, Monoclonal, Humanized* / administration & dosage
  • Antibodies, Monoclonal, Humanized* / adverse effects
  • Cholesterol, LDL / blood*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Monitoring / methods
  • Ezetimibe* / administration & dosage
  • Ezetimibe* / adverse effects
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects
  • Hypercholesterolemia* / blood
  • Hypercholesterolemia* / drug therapy
  • Hypercholesterolemia* / epidemiology
  • Japan
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care

Substances

  • Antibodies, Monoclonal, Humanized
  • Cholesterol, LDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Ezetimibe
  • evolocumab

Associated data

  • ClinicalTrials.gov/NCT02634580