Efficacy and safety of combination simvastatin and colesevelam in patientswith primary hypercholesterolemia

PURPOSE: To examine the efficacy and safety of colesevelam hydrochloride, a novel, nonsystemic, lipid-lowering agent, when coadministered with startin g doses of simvastatin in a multicenter, randomized, double-blind, placebo- controlled trial. PATIENTS AND METHODS: Subjects with hypercholesterolemia (plasma low densit y lipoprotein [LDL] cholesterol level > 160 mg/dL and triglyceride level le ss than or equal to 300 mg/dL) were randomly assigned to receive daily dose s of placebo (n = 33), colesevelam 3.8 g (recommended dose, n = 37), simvas tatin 10 mg(n = 35), colesevelam 3.8 g with simvastatin 10 mg(n = 34), cole sevelam 2.3 g (low dose, n = 36), simvastatin 20 mg (n = 39), or colesevela m 2.3 g with simvastatin 20 mg (n = 37), for 6 weeks. RESULTS: Mean LDL cholesterol levels decreased relative to baseline in the placebo group (P < 0.05) and in all active treatment groups (P < 0.0001). F or groups treated with combination therapy, the mean reduction in LDL chole sterol level was 42% (-80 mg/dL; P (0.0001 compared with baseline), which e xceeded the reductions for simvastatin 10 mg (-26%, -48 mg/dL) or 20 mg (-3 4%, -61 mg/dL) alone, or for colesevelam 2.3 g (-8%, -17 mg/dL) or 3.8 g (- 16%, -31 mg/dL) alone (P < 0.001). The effects of combination therapy on se rum HDL cholesterol and triglyceride levels were similar to those for simva statin alone. Side effects were similar among treatment groups, and there w ere no clinically important changes in laboratory parameters. CONCLUSION: Coadministration of colesevelam and simvastatin was effective a nd well tolerated, providing additive reductions in LDL cholesterol levels compared with either agent alone. <(c)> 2001 by Excerpta Medica, Inc.