Colesevelam hydrochloride (Cholestagel) - A new, potent bile acid sequestrant associated with a low incidence of gastrointestinal side effects

Objectives: To compare colesevelam hydrochloride (Cholestagel), a nonabsorb ed hydrogel with bile acid-sequestering properties, with placebo for its li pid-lowering efficacy, its effects on laboratory and clinical safety parame ters, and the incidence of adverse events. Methods: Following diet and placebo lead-in periods, placebo or colesevelam was administered at 4 dosages (1.5, 2.25, 3.0, or 3.75 g/d) for 6 weeks wi th morning and evening meals to men and women with hypercholesterolemia (lo w-density lipoprotein cholesterol level >4.14 mmol/L [>160 mg/dL]). Patient s returned to the clinic every 2 weeks throughout the treatment period for lipid parameter measurements and adverse event assessments. Samples were co llected for serum chemistry pro files, hematologic studies, coagulation stu dies, and vitamin level assessment at baseline and after 6 weeks of treatme nt. Results: Among the 149 patients randomized, 137 completed the study. Low-de nsity lipoprotein cholesterol concentrations decreased in a dosage-dependen t manner by 0.11 mmol/L (4.2 mg/dL) (1.8%) in the 1.5-g/d colesevelam treat ment group and up to 1.01 mmol/L (39 mg/dL) (19.1%) in the 3.75-g/d colesev elam treatment group. Low-density lipoprotein cholesterol concentrations at the end of treatment were significantly reduced from baseline levels in th e 3.0- and 3.75-g/d colesevelam treatment groups (P =.01 and P<.001, respec tively). Total cholesterol levels demonstrated a similar response to colese velam treatment, with an 8.1%, decrease from baseline in the 3.75-g/d treat ment group (P<.001). High-density lipoprotein cholesterol levels rose signi ficantly in the 3.0- and 3.75-g/d colesevelam treatment groups, by 11.2% (P =.006) and 8.1% (P=.02), respectively. Median triglyceride levels did not c hange from baseline, nor were there any significant differences between tre atment groups. The incidence of adverse events was similar among all groups . Conclusions: Colesevelam therapy is effective for lowering low-density lipo protein cholesterol concentrations in persons with moderate hypercholestero lemia. It lacks the constipating effect of other bile acid sequestrants, de monstrating the potential for increased compliance.