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

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.].

• Authors: Eli M Roth, James M McKenney, Maureen T Kelly, Carolyn M Setze, Dawn M Carlson, Alex Gold, James C Stolzenbach, Laura A Williams, Peter H Jones
• Journal: American journal of cardiovascular drugs : drugs, devices, and other interventions (Am J Cardiovasc Drugs) Vol. 10 Issue 3 Pg. 175-86 ( 2010) ISSN: 1175-3277 [Print] New Zealand
• PMID: 20524719 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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