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. 2009 Feb 3;24(6):467–474. doi: 10.1002/clc.4960240610

Low‐dose combination therapy with colesevelam hydrochloride and lovastatin effectively decreases low‐density lipoprotein cholesterol in patients with primary hypercholesterolemia

Michael H Davidson 1, Phillip Toth 2, Stuart Weiss 3, James Mckenney 4, Donald Hunninghake 5, Jonathan Isaacsohn 6, Joanne M Donovan 7,✉, Steven K Burke 7
PMCID: PMC6655189  PMID: 11403509

Abstract

Background: Colesevelam hydrochloride is a novel, lipid‐lowering agent that binds bile acids with high affinity. A multicenter, randomized, double‐blind, placebo‐controlled, parallel‐design study was conducted to assess the efficacy and tolerability of combination low‐dose colesevelam and lovastatin treatment in patients with primary hypercholesterolemia.

Hypothesis: Combination therapy with low doses of colesevelam and lovastatin decreases low density (LDL) cholesterol with minimal adverse events.

Methods: Following a 4‐ to 6‐week dietary lead in, 135 patients were randomized 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 (dosed apart).

Results: Combination colesevelam and lovastatin treatment decreased LDL cholesterol 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%). Both combination treatments reduced total cholesterol by 21% (p < 0.0001) and apolipoprotein B by 24% (p < 0.0001). Neither combination treatment significantly altered high‐density lipoprotein cholesterol or triglycerides. Adverse side effects were not significantly different among randomized groups.

Conclusions: Combination colesevelam and lovastatin was efficacious and well tolerated, resulting in additive decreases in LDL cholesterol levels whether or not both agents were administered simultaneously.

Keywords: hypercholesterolemia, lipid‐lowering therapy, bile acid sequestrants, 3‐hydroxy‐3‐methylglutaryl coenzyme A reductase inhibitors, combination lipid‐lowering therapy

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