Fixed-Dose Combination Fenofibrate/Pravastatin 160/40 mg Versus Simvastatin 20 mg Monotherapy in Adults With Type 2 Diabetes and Mixed Hyperlipidemia Uncontrolled With Simvastatin 20 mg: A Double-Blind, Randomized Comparative Study

Michel Farnier, Armin Steinmetz, Kjetil Retterstøl, A. Császár

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: Patients with type 2 diabetes mellitus and mixed hyperlipidemia have an increased cardiovascular risk and may not achieve recommended LDL-C and non-HDL-C goals on statin monotherapy. This study was designed to obtain regulatory approval of a fenofibrate/pravastatin 160/40 mg fixed-dose combination (FDC) capsule. Objective: The aim of this study was to compare the efficacy and tolerability of this FDC and simvastatin 20 mg in patients with type 2 diabetes. Methods: This multicenter, randomized, double-blind, parallel-arm study was conducted in patients with type 2 diabetes and mixed hyperlipidemia, without cardiovascular disease, and who were not at lipid goals with simvastatin 20 mg monotherapy. After a 6-week run-in period during which patients received simvastatin 20 mg, those with non-HDL-C concentrations ≥130 mg/dL or LDL-C concentrations ≥100 mg/dL and triglyceride concentrations 150 to 600 mg/dL were enrolled. Eligible patients were randomly assigned to receive 12-week treatment with fenofibrate/pravastatin 160/40 mg FDC or simvastatin 20 mg once daily, followed by a 12-week open-label tolerability-assessment period during which all patients received the FDC. The primary efficacy outcome was the mean percentage change in non-HDL-C after 12 weeks. Secondary efficacy outcomes included changes in other lipid and lipoprotein parameters, fibrinogen, and high-sensitivity C-reactive protein. Tolerability was assessed based on the prevalence of adverse events and abnormal laboratory data in each treatment group. Results: A total of 291 patients were randomized to receive fenofibrate/pravastatin (n= 145) or simvastatin (n = 146). The mean (SD) age of the participants was 56.6 (8.9) years, 48.1% were men, and the body mass index was 31.3 (4.6) kg/m2. The FDC was associated with a significantly greater reduction in non-HDL-C (primary end point) compared with simvastatin monotherapy (-12.9% [1.8] vs -6.8% [1.8]; P = 0.008). Triglyceride (-28.6% [3.7] vs +5.0% [3.6]; P <0.001), fibrinogen (-11.5% [1.6] vs +0.3% [1.6]; P <0.001), and HDL-C (+6.3% [1.3] vs +1.8% [1.3]; P = 0.008) concentrations also were significantly improved with the FDC compared with simvastatin monotherapy. The proportions of patients who achieved the LDL-C target (

Original languageEnglish
Pages (from-to)1-12
Number of pages12
JournalClinical Therapeutics
Volume33
Issue number1
DOIs
Publication statusPublished - Jan 2011

Fingerprint

Fenofibrate
Pravastatin
Simvastatin
Hyperlipidemias
Type 2 Diabetes Mellitus
Fibrinogen
Triglycerides
Lipids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
C-Reactive Protein
Lipoproteins
Capsules
Body Mass Index
Cardiovascular Diseases

Keywords

  • Combination therapy
  • Fenofibrate
  • Mixed hyperlipidemia
  • Pravastatin
  • Type 2 diabetes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

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title = "Fixed-Dose Combination Fenofibrate/Pravastatin 160/40 mg Versus Simvastatin 20 mg Monotherapy in Adults With Type 2 Diabetes and Mixed Hyperlipidemia Uncontrolled With Simvastatin 20 mg: A Double-Blind, Randomized Comparative Study",
abstract = "Background: Patients with type 2 diabetes mellitus and mixed hyperlipidemia have an increased cardiovascular risk and may not achieve recommended LDL-C and non-HDL-C goals on statin monotherapy. This study was designed to obtain regulatory approval of a fenofibrate/pravastatin 160/40 mg fixed-dose combination (FDC) capsule. Objective: The aim of this study was to compare the efficacy and tolerability of this FDC and simvastatin 20 mg in patients with type 2 diabetes. Methods: This multicenter, randomized, double-blind, parallel-arm study was conducted in patients with type 2 diabetes and mixed hyperlipidemia, without cardiovascular disease, and who were not at lipid goals with simvastatin 20 mg monotherapy. After a 6-week run-in period during which patients received simvastatin 20 mg, those with non-HDL-C concentrations ≥130 mg/dL or LDL-C concentrations ≥100 mg/dL and triglyceride concentrations 150 to 600 mg/dL were enrolled. Eligible patients were randomly assigned to receive 12-week treatment with fenofibrate/pravastatin 160/40 mg FDC or simvastatin 20 mg once daily, followed by a 12-week open-label tolerability-assessment period during which all patients received the FDC. The primary efficacy outcome was the mean percentage change in non-HDL-C after 12 weeks. Secondary efficacy outcomes included changes in other lipid and lipoprotein parameters, fibrinogen, and high-sensitivity C-reactive protein. Tolerability was assessed based on the prevalence of adverse events and abnormal laboratory data in each treatment group. Results: A total of 291 patients were randomized to receive fenofibrate/pravastatin (n= 145) or simvastatin (n = 146). The mean (SD) age of the participants was 56.6 (8.9) years, 48.1{\%} were men, and the body mass index was 31.3 (4.6) kg/m2. The FDC was associated with a significantly greater reduction in non-HDL-C (primary end point) compared with simvastatin monotherapy (-12.9{\%} [1.8] vs -6.8{\%} [1.8]; P = 0.008). Triglyceride (-28.6{\%} [3.7] vs +5.0{\%} [3.6]; P <0.001), fibrinogen (-11.5{\%} [1.6] vs +0.3{\%} [1.6]; P <0.001), and HDL-C (+6.3{\%} [1.3] vs +1.8{\%} [1.3]; P = 0.008) concentrations also were significantly improved with the FDC compared with simvastatin monotherapy. The proportions of patients who achieved the LDL-C target (",
keywords = "Combination therapy, Fenofibrate, Mixed hyperlipidemia, Pravastatin, Type 2 diabetes",
author = "Michel Farnier and Armin Steinmetz and Kjetil Retterst{\o}l and A. Cs{\'a}sz{\'a}r",
year = "2011",
month = "1",
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language = "English",
volume = "33",
pages = "1--12",
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T1 - Fixed-Dose Combination Fenofibrate/Pravastatin 160/40 mg Versus Simvastatin 20 mg Monotherapy in Adults With Type 2 Diabetes and Mixed Hyperlipidemia Uncontrolled With Simvastatin 20 mg

T2 - A Double-Blind, Randomized Comparative Study

AU - Farnier, Michel

AU - Steinmetz, Armin

AU - Retterstøl, Kjetil

AU - Császár, A.

PY - 2011/1

Y1 - 2011/1

N2 - Background: Patients with type 2 diabetes mellitus and mixed hyperlipidemia have an increased cardiovascular risk and may not achieve recommended LDL-C and non-HDL-C goals on statin monotherapy. This study was designed to obtain regulatory approval of a fenofibrate/pravastatin 160/40 mg fixed-dose combination (FDC) capsule. Objective: The aim of this study was to compare the efficacy and tolerability of this FDC and simvastatin 20 mg in patients with type 2 diabetes. Methods: This multicenter, randomized, double-blind, parallel-arm study was conducted in patients with type 2 diabetes and mixed hyperlipidemia, without cardiovascular disease, and who were not at lipid goals with simvastatin 20 mg monotherapy. After a 6-week run-in period during which patients received simvastatin 20 mg, those with non-HDL-C concentrations ≥130 mg/dL or LDL-C concentrations ≥100 mg/dL and triglyceride concentrations 150 to 600 mg/dL were enrolled. Eligible patients were randomly assigned to receive 12-week treatment with fenofibrate/pravastatin 160/40 mg FDC or simvastatin 20 mg once daily, followed by a 12-week open-label tolerability-assessment period during which all patients received the FDC. The primary efficacy outcome was the mean percentage change in non-HDL-C after 12 weeks. Secondary efficacy outcomes included changes in other lipid and lipoprotein parameters, fibrinogen, and high-sensitivity C-reactive protein. Tolerability was assessed based on the prevalence of adverse events and abnormal laboratory data in each treatment group. Results: A total of 291 patients were randomized to receive fenofibrate/pravastatin (n= 145) or simvastatin (n = 146). The mean (SD) age of the participants was 56.6 (8.9) years, 48.1% were men, and the body mass index was 31.3 (4.6) kg/m2. The FDC was associated with a significantly greater reduction in non-HDL-C (primary end point) compared with simvastatin monotherapy (-12.9% [1.8] vs -6.8% [1.8]; P = 0.008). Triglyceride (-28.6% [3.7] vs +5.0% [3.6]; P <0.001), fibrinogen (-11.5% [1.6] vs +0.3% [1.6]; P <0.001), and HDL-C (+6.3% [1.3] vs +1.8% [1.3]; P = 0.008) concentrations also were significantly improved with the FDC compared with simvastatin monotherapy. The proportions of patients who achieved the LDL-C target (

AB - Background: Patients with type 2 diabetes mellitus and mixed hyperlipidemia have an increased cardiovascular risk and may not achieve recommended LDL-C and non-HDL-C goals on statin monotherapy. This study was designed to obtain regulatory approval of a fenofibrate/pravastatin 160/40 mg fixed-dose combination (FDC) capsule. Objective: The aim of this study was to compare the efficacy and tolerability of this FDC and simvastatin 20 mg in patients with type 2 diabetes. Methods: This multicenter, randomized, double-blind, parallel-arm study was conducted in patients with type 2 diabetes and mixed hyperlipidemia, without cardiovascular disease, and who were not at lipid goals with simvastatin 20 mg monotherapy. After a 6-week run-in period during which patients received simvastatin 20 mg, those with non-HDL-C concentrations ≥130 mg/dL or LDL-C concentrations ≥100 mg/dL and triglyceride concentrations 150 to 600 mg/dL were enrolled. Eligible patients were randomly assigned to receive 12-week treatment with fenofibrate/pravastatin 160/40 mg FDC or simvastatin 20 mg once daily, followed by a 12-week open-label tolerability-assessment period during which all patients received the FDC. The primary efficacy outcome was the mean percentage change in non-HDL-C after 12 weeks. Secondary efficacy outcomes included changes in other lipid and lipoprotein parameters, fibrinogen, and high-sensitivity C-reactive protein. Tolerability was assessed based on the prevalence of adverse events and abnormal laboratory data in each treatment group. Results: A total of 291 patients were randomized to receive fenofibrate/pravastatin (n= 145) or simvastatin (n = 146). The mean (SD) age of the participants was 56.6 (8.9) years, 48.1% were men, and the body mass index was 31.3 (4.6) kg/m2. The FDC was associated with a significantly greater reduction in non-HDL-C (primary end point) compared with simvastatin monotherapy (-12.9% [1.8] vs -6.8% [1.8]; P = 0.008). Triglyceride (-28.6% [3.7] vs +5.0% [3.6]; P <0.001), fibrinogen (-11.5% [1.6] vs +0.3% [1.6]; P <0.001), and HDL-C (+6.3% [1.3] vs +1.8% [1.3]; P = 0.008) concentrations also were significantly improved with the FDC compared with simvastatin monotherapy. The proportions of patients who achieved the LDL-C target (

KW - Combination therapy

KW - Fenofibrate

KW - Mixed hyperlipidemia

KW - Pravastatin

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