Efficacy and safety of fenofibric acid co-administered with low- or moderate-dose statin in patients with mixed dyslipidemia and type 2 diabetes mellitus: results of a pooled subgroup analysis from three randomized, controlled, double-blind trials.

Abstract

BACKGROUND:

Monotherapy with lipid-modifying medication is frequently insufficient to normalize lipid abnormalities in patients with mixed dyslipidemia and type 2 diabetes mellitus.

OBJECTIVE:

To evaluate the efficacy and safety of fenofibric acid + statin combination therapy in this population.

STUDY DESIGN:

A pooled, subgroup analysis of three randomized, controlled, double-blind, 12-week trials.

SETTING:

Multiple clinical research facilities in the US and Canada.

PATIENTS:

Patients with mixed dyslipidemia and type 2 diabetes (n = 586).

INTERVENTION:

Fenofibric acid (Trilipix) 135 mg monotherapy; low-, moderate-, or high-dose statin monotherapy (rosuvastatin [Crestor] 10, 20, or 40 mg; simvastatin [Zocor] 20, 40, or 80 mg; or atorvastatin [Lipitor] 20, 40, or 80 mg); or fenofibric acid + low- or moderate-dose statin.

MAIN OUTCOME MEASURE:

Mean percentage changes in lipid parameters, percentages of patients achieving optimal serum lipid/apolipoprotein levels, and incidence of adverse events.

RESULTS:

Fenofibric acid + low-dose statin resulted in significantly (p < 0.001) greater mean percentage changes in high-density lipoprotein cholesterol (HDL-C) [16.8%] and triglycerides (-43.9%) than low-dose statin monotherapy (4.7% and -18.1%, respectively) and significantly (p < 0.001) greater reductions in low-density lipoprotein cholesterol (LDL-C) [-34.0%] than fenofibric acid monotherapy (-5.3%). Similarly, fenofibric acid + moderate-dose statin resulted in significantly (p < or = 0.011) greater mean percentage changes in HDL-C (16.3%) and triglycerides (-43.4%) than moderate-dose statin monotherapy (8.7% and -24.2%, respectively) and significantly (p < 0.001) greater reductions in LDL-C (-32.6%) than fenofibric acid monotherapy (-5.3%). Compared with low- or moderate-dose statin, fenofibric acid + low- or moderate-dose statin resulted in over 5-fold higher percentages of patients achieving optimal levels of LDL-C, non-HDL-C, apolipoprotein B, HDL-C, and triglycerides simultaneously. Incidence of adverse events was generally similar among treatments.

CONCLUSION:

Fenofibric acid + statin combination therapy in patients with mixed dyslipidemia and type 2 diabetes was well tolerated and resulted in more comprehensive improvement in the lipid/apolipoprotein profile than either monotherapy. [Clinical trials are registered at www.clinicaltrials.gov: NCT00300482, NCT00300456, and NCT00300469].

• Authors: Peter H Jones, Kenneth Cusi, Michael H Davidson, Maureen T Kelly, Carolyn M Setze, Kamlesh Thakker, Darryl J Sleep, James C Stolzenbach
• Journal: American journal of cardiovascular drugs : drugs, devices, and other interventions (Am J Cardiovasc Drugs) Vol. 10 Issue 2 Pg. 73-84 ( 2010) ISSN: 1175-3277 [Print] New Zealand
• PMID: 20136164 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Fluorobenzenes
• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Hypolipidemic Agents
• Pyrimidines
• Pyrroles
• Sulfonamides
• Rosuvastatin Calcium
• Atorvastatin
• Simvastatin
• fenofibric acid
• Fenofibrate

Topics

• Aged
• Atorvastatin
• Clinical Trials, Phase III as Topic
• Diabetes Mellitus, Type 2 (complications)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Therapy, Combination
• Dyslipidemias (complications, drug therapy)
• Female
• Fenofibrate (administration & dosage, adverse effects, analogs & derivatives, therapeutic use)
• Fluorobenzenes (administration & dosage, adverse effects, therapeutic use)
• Heptanoic Acids (administration & dosage, adverse effects, therapeutic use)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Hypolipidemic Agents (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Pyrimidines (administration & dosage, adverse effects, therapeutic use)
• Pyrroles (administration & dosage, adverse effects, therapeutic use)
• Randomized Controlled Trials as Topic
• Rosuvastatin Calcium
• Simvastatin (administration & dosage, adverse effects, therapeutic use)
• Sulfonamides (administration & dosage, adverse effects, therapeutic use)