Efficacy and safety of rosuvastatin and fenofibric acid combination therapy versus simvastatin monotherapy in patients with hypercholesterolemia and hypertriglyceridemia: a randomized, double-blind study

Am J Cardiovasc Drugs. 2010;10(3):175-86. doi: 10.2165/11533430-000000000-00000.

Abstract

Objectives: To evaluate the efficacy and safety of fixed-dose combinations of rosuvastatin and fenofibric acid (rosuvastatin/fenofibric acid) compared with simvastatin in patients with high levels of low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG).

Background: Combination therapy with a statin and a fibrate is one of the treatment options to manage multiple lipid abnormalities in patients with hypercholesterolemia and elevated TGs.

Methods: In this randomized, double-blind study, patients (n = 474) with LDL-C > or =160 mg/dL and < or =240 mg/dL and TG > or =150 mg/dL and <400 mg/dL were treated for 8 weeks with simvastatin 40 mg, rosuvastatin/fenofibric acid 5 mg/135 mg, rosuvastatin/fenofibric acid 10 mg/135 mg, or rosuvastatin/fenofibric acid 20 mg/135 mg. Primary and secondary variables were mean percent changes in LDL-C comparing rosuvastatin/fenofibric acid 20 mg/135 mg with simvastatin 40 mg and rosuvastatin/fenofibric acid 10 mg/135 mg and rosuvastatin/fenofibric acid 5 mg/135 mg with simvastatin 40 mg, respectively. Additional efficacy variables included non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein (Apo) B, HDL-C, TG, and high-sensitivity C-reactive protein (hsCRP). Safety was evaluated based on data collected for adverse events (AEs), physical and electrocardiographic examinations, vital sign measurements, and clinical laboratory tests.

Results: Significantly greater reductions in LDL-C levels from baseline values were observed with the combination of rosuvastatin/fenofibric acid 20 mg/135 mg (-47.2%, p < 0.001), rosuvastatin/fenofibric acid 10 mg/135 mg (-46.0%, p < 0.001), and rosuvastatin/fenofibric acid 5 mg/135 mg (-38.9%, p = 0.007) than with simvastatin 40 mg (-32.8%). Significant (p < or = 0.04 for all comparisons) improvements in non-HDL-C, ApoB, HDL-C, TG, and hsCRP levels were also observed with each of the rosuvastatin/fenofibric acid doses as compared with simvastatin 40 mg. Treatment-related AEs and discontinuations due to AEs were similar across groups. The incidence of serious AEs was 0% with simvastatin 40 mg, 3.4% with rosuvastatin/fenofibric acid 5 mg/135 mg, 0.8% with rosuvastatin/fenofibric acid 10 mg/135 mg, and 2.5% with rosuvastatin/fenofibric acid 20 mg/135 mg. No cases of rhabdomyolysis or drug-related myopathy were reported.

Conclusion: In patients with high LDL-C and TG levels, combination treatment with rosuvastatin/fenofibric acid was well tolerated, and each of the rosuvastatin/fenofibric acid doses produced greater reductions in LDL-C and improvements in other efficacy parameters, compared with simvastatin 40 mg. [Clinical trial is registered at www.clinicaltrials.gov NCT00812955.].

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anticholesteremic Agents / therapeutic use*
  • Cholesterol, HDL / blood
  • Cholesterol, LDL / blood
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Fenofibrate / administration & dosage
  • Fenofibrate / adverse effects
  • Fenofibrate / analogs & derivatives*
  • Fluorobenzenes / administration & dosage*
  • Fluorobenzenes / adverse effects
  • Humans
  • Hypercholesterolemia / drug therapy*
  • Hypertriglyceridemia / drug therapy*
  • Liver / drug effects
  • Male
  • Middle Aged
  • Pyrimidines / administration & dosage*
  • Pyrimidines / adverse effects
  • Rosuvastatin Calcium
  • Simvastatin / adverse effects
  • Simvastatin / therapeutic use*
  • Sulfonamides / administration & dosage*
  • Sulfonamides / adverse effects

Substances

  • Anticholesteremic Agents
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Fluorobenzenes
  • Pyrimidines
  • Sulfonamides
  • Rosuvastatin Calcium
  • Simvastatin
  • fenofibric acid
  • Fenofibrate

Associated data

  • ClinicalTrials.gov/NCT00812955