Effectiveness of colesevelam hydrochloride in decreasing LDL cholesterol in patients with primary hypercholesterolemia: A 24-week randomized controlled trial

Objective: To evaluate the efficacy, tolerability, and safety of colesevela m hydrochloride, a new nonsystemic lipid-lowering agent. Patients and Methods: In this double-blind, placebo-controlled trial perfor med in 1998, 494 patients with primary hypercholesterolemia (low-density li poprotein [LDL] cholesterol level greater than or equal to 130 mg/dL and le ss than or equal to 220 mg/dL) were randomized to receive placebo or colese velam (2.3 g/d, 3.0 g/d, 3.8 g/d, or 4.5 g/d) for 24 weeks. Fasting serum l ipid profiles were measured to assess efficacy. Adverse events were monitor ed, and discontinuation rates and compliance rates were analyzed. The prima ry outcome measure was the mean absolute change of LDL cholesterol from bas eline to the end of the 24-week treatment period. Results: Colesevelam lowered mean LDL cholesterol levels 9% to 18% in a dos e-dependent manner (P < .001), with a median LDL cholesterol reduction of 2 0% at 4.5 g/d. The reduction in LDL cholesterol levels was maximal after 2 weeks and sustained throughout the study. Mean total cholesterol levels dec reased 4% to 10% (P < .001), while median high-density lipoprotein choleste rol levels increased 3% to 4% (P < .001). Median triglyceride levels increa sed by 5% to 10% in placebo and colesevelam treatment groups relative to ba seline (P < .05), but none of these differences were significantly differen t from placebo. Mean apolipoprotein B levels decreased 6% to 12% in an appa rent dose-dependent manner (P<.001). No significant differences occurred in adverse events or discontinuation rates between groups, and compliance rat es were between 88% and 92% for all groups. Conclusions: Colesevelam was efficacious, decreasing mean LDL cholesterol l evels by up to 18%, and well tolerated without serious adverse events.