Ezetimibe and Rosuvastatin Combination Treatment Can Reduce the Dose of Rosuvastatin Without Compromising Its Lipid-lowering Efficacy

Clin Ther. 2019 Dec;41(12):2571-2592. doi: 10.1016/j.clinthera.2019.10.010. Epub 2019 Nov 11.

Abstract

Purpose: The goal of this study was to compare the lipid-lowering efficacy of the combination of ezetimibe and low- or intermediate-intensity statin therapy versus that of high-intensity statin monotherapy.

Methods: This study is a post hoc analysis of an 8-week, randomized, double-blind, Phase III trial. Patients who had hypercholesterolemia and required lipid-lowering treatment were randomly assigned to 1 of 6 treatment groups: rosuvastatin 5 mg (R5, n = 68), rosuvastatin 10 mg (R10, n = 67), rosuvastatin 20 mg (R20, n = 69), and ezetimibe 10 mg combined with rosuvastatin 5 mg (R5 + E10, n = 67), rosuvastatin 10 mg (R10 + E10, n = 68), and rosuvastatin 20 mg (R20 + E10, n = 68) daily. The effects of coadministration of ezetimibe and a low dose of rosuvastatin on lipid parameters and the target achievement rate were compared between the R5 + E10 and R10 treatment groups, the R5 + E10 and R20 treatment groups, and the R10 + E10 and R20 treatment groups.

Findings: Reductions in total cholesterol, LDL-C, apolipoprotein B, the apolipoprotein B/A1 ratio, and non-HDL-C were not different between the R5 + E10 and R10 treatment groups (all, P > 0.017), the R5 + E10 and R20 treatment groups (all, P > 0.017), and the R10 + E10 and R20 treatment groups (all, P > 0.017). R5 + E10 treatment showed efficacy comparable to that of R10 or R20 in affording LDL levels <50% of the baseline level (R5 + E10 vs R10, 73.13% vs 62.69% [P = 0.1952]; R5 + E10 vs R20, 73.13% vs 73.91% [P = 0.9180]), LDL-C levels <70 mg/dL (R5 + E10 vs R10, 64.18% vs 55.22% [P = 0.2906]; R5 + E10 vs R20, 64.18% vs 62.32% [P = 0.8220]), and LDL-C levels <50% of the baseline level or <70 mg/dL (R5 + E10 vs R10, 77.61% vs 70.15% [P = 0.3255]; R5 + E10 vs R20, 77.61% vs 78.26% [P = 0.9273]). The R10 + E10 treatment group was better than the R20 treatment group in achieving the target LDL-C level <70 mg/dL (83.82% vs 62.32%; P = 0.0046), even among participants with a baseline LDL-C level >135 mg/dL (77.5% vs 48.8%, respectively; P = 0.0074).

Implications: Ezetimibe combined with low- or intermediate-intensity statin therapy has lipid-lowering efficacy comparable to or better than that of high-intensity rosuvastatin monotherapy. The results of the present study indicate that the combination treatment with ezetimibe is advantageous in that it permits dose reduction of rosuvastatin without compromising the lipid-lowering efficacy of rosuvastatin. ClinicalTrials.gov identifier: NCT02205606.

Keywords: Combination therapy; Ezetimibe; Hypercholesterolemia; Rosuvastatin.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticholesteremic Agents* / administration & dosage
  • Anticholesteremic Agents* / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Ezetimibe* / administration & dosage
  • Ezetimibe* / therapeutic use
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Lipids / blood
  • Rosuvastatin Calcium* / administration & dosage
  • Rosuvastatin Calcium* / therapeutic use
  • Treatment Outcome

Substances

  • Anticholesteremic Agents
  • Lipids
  • Rosuvastatin Calcium
  • Ezetimibe

Associated data

  • ClinicalTrials.gov/NCT02205606