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.
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.


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


METHODS
Multiple clinical research facilities in the US and Canada.


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


METHODS
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.


METHODS
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.


CONCLUSIONS
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].
Jones
Peter H
PH
Baylor College of Medicine, Houston, Texas, USA. jones@bcm.tmc.edu
Cusi
Kenneth
K
Davidson
Michael H
MH
Kelly
Maureen T
MT
Setze
Carolyn M
CM
Thakker
Kamlesh
K
Sleep
Darryl J
DJ
Stolzenbach
James C
JC
D000368:Aged; D000069059:Atorvastatin; D017326:Clinical Trials, Phase III as Topic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D050171:Dyslipidemias / Q000150:complications / Q000188:drug therapy*; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005464:Fluorobenzenes / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D000068718:Rosuvastatin Calcium; D019821:Simvastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use
D005464:Fluorobenzenes; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D019821:Simvastatin; C006012:fenofibric acid; D011345:Fenofibrate