Safety and efficacy of colesevelam hydrochloride in combination with fenofibrate for the treatment of mixed hyperlipidemia.
OBJECTIVE
The aim of this study was to evaluate the amount of low-density lipoprotein cholesterol (LDL-C) reduction achieved by adding the specifically engineered bile acid sequestrant (SE-BAS) colesevelam HCl to a stable dose of fenofibrate in patients with mixed hyperlipidemia.


METHODS
Patients with mixed hyperlipidemia (n = 129) were enrolled in a randomized, double-blind, placebo-controlled, parallel-group study investigating the efficacy of fenofibrate plus colesevelam HCl versus fenofibrate monotherapy. After a 4- to 8-week washout period, subjects received fenofibrate 160 mg/day for 8 weeks and were then randomized to receive colesevelam HCl 3.75 g/day or placebo, in addition to fenofibrate 160 mg/day, for 6 weeks.


METHODS
The primary efficacy endpoint was mean percent change in LDL-C during randomized treatment. Secondary endpoints included absolute and percent changes in mean levels of LDL-C, triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, total cholesterol (TC), and apolipoproteins (apo) A-I and B during randomized treatment and from washout to end of randomized treatment.


RESULTS
Of the 129 patients randomized to treatment, 119 completed the study. After 6 weeks of treatment, fenofibrate plus colesevelam HCl produced a mean percent change in LDL-C of -10.4% versus +2.3% with fenofibrate monotherapy (p < 0.0001). Fenofibrate plus colesevelam HCl was significantly more effective than fenofibrate alone at reducing levels of non-HDL-C, TC, and apo B (p < or = 0.0002). Colesevelam HCl did not significantly affect the TG-lowering effects of fenofibrate. Both treatment regimens were safe and well tolerated.


CONCLUSIONS
Compared with fenofibrate monotherapy in patients with mixed hyperlipidemia, fenofibrate/colesevelam HCl combination therapy significantly reduced mean LDL-C, non-HDL-C, TC, and apo B levels without significantly affecting the TG-lowering or HDL-C-raising effects of fenofibrate. Fenofibrate/colesevelam HCl combination therapy is a safe, useful alternative for the treatment of mixed hyperlipidemia.
McKenney
James
J
National Clinical Research, Inc., Richmond, VA 23294, USA. jmckenney@ncrinc.net
Jones
Michael
M
Abby
Stacey
S
D000499:Allylamine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000069472:Colesevelam Hydrochloride; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006954:Hyperlipoproteinemia Type V / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012449:Safety; D016896:Treatment Outcome
D000960:Hypolipidemic Agents; D000499:Allylamine; D000069472:Colesevelam Hydrochloride; D011345:Fenofibrate