title: A randomized crossover trial of combination pharmacologic therapy in children with familial hyperlipidemia.
abstract: We sought to determine whether a low-dose combination of a bile acid-binding resin (colestipol) with an hydroxymethylglutaryl CoA reductase inhibitor (pravastatin) would result in improved acceptability, compliance, and effectiveness in lipid-lowering compared with conventional therapy with a higher dose of a bile acid-binding resin only, with fewer side effects. We performed a randomized, crossover open-label clinical trial with two 18-wk medication regimens separated by an 8-wk washout period in 36 children and adolescents with familial hypercholesterolemia or familial combined hyperlipidemia. The regimens included colestipol 10 g/d (10 pills) versus a combination of colestipol 5 g/d with pravastatin 10 mg/d (six pills). All patients were maintained on a fat-reduced diet. Acceptability was better with the combination regimen. Mean compliance was similar and suboptimal (approximately 60%) with all medication components. Mean relative LDL cholesterol lowering was significantly better with the combination regimen (-17 +/- 16% versus -10 +/- 13%; p = 0.045), although insufficient to achieve recommended target values in the majority of patients on either regimen. Both regimens were equally free of adverse effects, with no important effect on chemistry or hematologic values. Patient-reported adverse effects were more common with the conventional-dose colestipol-only regimen. Compliance with medication regimens using the bile acid-binding resins is suboptimal, although combination with a low dose of a statin may result in better lipid lowering.
authors.affiliation: Department of Pediatrics, University of Toronto, The Hospital for Sick Children, Toronto, Canada. brian.mccrindle@sickkids.ca
authors.forename: Brian W
authors.initials: BW
authors.lastname: McCrindle
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Helden
authors.forename: Geraldine
authors.initials: G
authors.lastname: Cullen-Dean
authors.forename: William T
authors.initials: WT
authors.lastname: Conner
mesh_terms: D000293:Adolescent; D002648:Child; D003084:Colestipol / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D010349:Patient Compliance; D018579:Patient Selection; D017035:Pravastatin / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D003084:Colestipol; D017035:Pravastatin