Safety and efficacy of colesevelam hydrochloride in combination with fenofibrate for the treatment of mixed hyperlipidemia

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Abstract
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. Research design and 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. Main outcomes measures: 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 pro-duced 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 ≤ 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.