OBJECTIVE: To evaluate the efficacy, tolerability, and safety of colesevelam hydrochloride, a new nonsystemic lipid-lowering agent. PATIENTS AND METHODS: In this double-blind, placebo-controlled trial performed in 1998, 494 patients with primary hypercholesterolemia (low-density lipoprotein [LDL] cholesterol level > or = 130 mg/dL and < or = 220 mg/dL) were randomized to receive placebo or colesevelam (2.3 g/d, 3.0 g/d, 3.8 g/d, or 4.5 g/d) for 24 weeks. Fasting serum lipid profiles were measured to assess efficacy. Adverse events were monitored, and discontinuation rates and compliance rates were analyzed. The primary outcome measure was the mean absolute change of LDL cholesterol from baseline to the end of the 24-week treatment period. RESULTS: Colesevelam lowered mean LDL cholesterol levels 9% to 18% in a dose-dependent manner (P<.001), with a median LDL cholesterol reduction of 20% 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 decreased 4% to 10% (P<.001), while median high-density lipoprotein cholesterol levels increased 3% to 4% (P<.001). Median triglyceride levels increased by 5% to 10% in placebo and colesevelam treatment groups relative to baseline (P<.05), but none of these differences were significantly different from placebo. Mean apolipoprotein B levels decreased 6% to 12% in an apparent dose-dependent manner (P<.001). No significant differences occurred in adverse events or discontinuation rates between groups, and compliance rates were between 88% and 92% for all groups. CONCLUSIONS: Colesevelam was efficacious, decreasing mean LDL cholesterol levels by up to 18%, and well tolerated without serious adverse events.
RCT Entities:
OBJECTIVE: To evaluate the efficacy, tolerability, and safety of colesevelam hydrochloride, a new nonsystemic lipid-lowering agent. PATIENTS AND METHODS: In this double-blind, placebo-controlled trial performed in 1998, 494 patients with primary hypercholesterolemia (low-density lipoprotein [LDL] cholesterol level > or = 130 mg/dL and < or = 220 mg/dL) were randomized to receive placebo or colesevelam (2.3 g/d, 3.0 g/d, 3.8 g/d, or 4.5 g/d) for 24 weeks. Fasting serum lipid profiles were measured to assess efficacy. Adverse events were monitored, and discontinuation rates and compliance rates were analyzed. The primary outcome measure was the mean absolute change of LDL cholesterol from baseline to the end of the 24-week treatment period. RESULTS:Colesevelam lowered mean LDL cholesterol levels 9% to 18% in a dose-dependent manner (P<.001), with a median LDL cholesterol reduction of 20% 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 decreased 4% to 10% (P<.001), while median high-density lipoprotein cholesterol levels increased 3% to 4% (P<.001). Median triglyceride levels increased by 5% to 10% in placebo and colesevelam treatment groups relative to baseline (P<.05), but none of these differences were significantly different from placebo. Mean apolipoprotein B levels decreased 6% to 12% in an apparent dose-dependent manner (P<.001). No significant differences occurred in adverse events or discontinuation rates between groups, and compliance rates were between 88% and 92% for all groups. CONCLUSIONS:Colesevelam was efficacious, decreasing mean LDL cholesterol levels by up to 18%, and well tolerated without serious adverse events.