Low-dose combination therapy with colesevelam hydrochloride and lovastatineffectively decreases low-density lipoprotein cholesterol in patients withprimary hypercholesterolemia

Background: Colesevelam hydrochloride is a novel, lipid-lowering agent that binds bile acids with high affinity. A multicenter, randomized, double-bli nd, placebo-controlled, parallel-design study was conducted to assess the e fficacy and tolerability of combination low-dose colesevelam and lovastatin treatment in patients with primary hypercholesterolemia. Hypothesis: Combination therapy with low doses of colesevelam and lovastati n decreases low density (LDL) cholesterol with minimal adverse events. Methods: Following a 4- to 6-week dietary lead in, 135 patients were random ized into five groups for a 4-week treatment period: placebo, colesevelam 2 .3 g at dinner, lovastatin 10 mg at dinner, the combination of colesevelam and lovastatin given at dinner (dosed together), and combination treatment with colesevelam given at dinner and lovastatin administered at bedtime (do sed apart). Results: Combination colesevelam and lovastatin treatment decreased LDL cho lesterol by 34% (60 mg/dl, p < 0.0001) and 32% (53 mg/dl, p < 0.0001) when colesevelam and lovastatin were dosed together or dosed apart, respectively . Both combination therapies were superior to either agent alone (p < 0.05) . Decreases in LDL cholesterol exceeded the combined decreases observed for colesevelam alone (13 mg/dl, 7%) and lovastatin alone (39 mg/dl, 22%). Bot h combination treatments reduced total cholesterol by 21% (p < 0.0001) and apolipoprotein B by 24% (p < 0.0001). Neither combination treatment signifi cantly altered high-density lipoprotein cholesterol or triglycerides. Adver se side effects were not significantly different among randomized groups. Conclusions: Combination colesevelam and lovastatin was efficacious and wel l tolerated, resulting in additive decreases in LDL cholesterol levels whet her or not both agents were administered simultaneously.