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.
Key words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Clinical TherapeuticsAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment Panel III). Third report of the national cholesterol education Program (NCEP) expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult treatment Panel III) final report.Circulation. 2002; 106: 3143-3421
- Interpretation of the evidence for the efficacy and safety of statin therapy.Lancet. 2016; 388: 2532-2561
- 2016 ESC/EAS guidelines for the management of dyslipidaemias.Eur Heart J. 2016; 37: 2999-3058
- 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines.J Am Coll Cardiol. 2014; 63: 2889-2934
- 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American heart association task force on clinical practice guidelines.Circulation. 2019; 139: e1082-e1143
- Achievement of 2011 European low-density lipoprotein cholesterol (LDL-C) goals of either <70 mg/dl or ≥50% reduction in high-risk patients: results from VOYAGER.Atherosclerosis. 2013; 228: 265-269
- Effect of fixed-dose combinations of ezetimibe plus rosuvastatin in patients with primary hypercholesterolemia: MRS-ROZE (Multicenter Randomized Study of ROsuvastatin and eZEtimibe).Cardiovasc Ther. 2016; 34: 371-382
- Ezetimibe added to statin therapy after acute coronary syndromes.N Engl J Med. 2015; 372: 2387-2397
- The role of ethnicity in variability in response to drugs: focus on clinical pharmacology studies.Clin Pharmacol Ther. 2008; 84: 417-423
- Statin dose in Asians: is pharmacogenetics relevant?.Pharmacogenomics. 2011; 12: 1605-1615
- Comparison of statin plus ezetimibe with double-dose statin on lipid profiles and inflammation markers.Lipids Health Dis. 2018; 17: 265
- Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis.JAMA. 2016; 316: 1289-1297
- The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.Lancet. 2012; 380: 581-590
- Low-density lipoprotein cholesterol in a global cohort of 57,885 statin-treated patients.Atherosclerosis. 2016; 255: 200-209
- Management of dyslipidaemia in patients with coronary heart disease: results from the ESC-EORP EUROASPIRE V survey in 27 countries.Atherosclerosis. 2019; 285: 135-146
- Adverse effects of statins—myths and reality.Curr Pharm Des. 2015; 21: 1220-1226
- Intermittent nondaily dosing strategies in patients with previous statin-induced myopathy.Ann Pharmacother. 2013; 47: 398-404
- Can we further optimize statin therapy to increase tolerability?.Expert Opin Drug Discov. 2019; 14: 843-847
- Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.JAMA. 2011; 305: 2556-2564
- Time- and dose-dependent association of statin use with risk of clinically relevant new-onset diabetes mellitus in primary prevention: a nationwide observational cohort study.J Am Heart Assoc. 2019; 8e011320
- Statin therapy with or without ezetimibe and the progression to diabetes.J Clin Lipidol. 2016; 10: 306-313
Article info
Publication history
Published online: November 11, 2019
Accepted:
October 9,
2019
Received in revised form:
October 3,
2019
Received:
July 30,
2019
Identification
Copyright
© 2019 Published by Elsevier Inc.
