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 lipidlowering 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 (Ϫ17 Ϯ 16% versus Ϫ10 Ϯ 13%; p ϭ 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. There is an extensive literature now documenting the effects of lipid-lowering pharmacologic therapy in reducing atherosclerotic cardiovascular disease and events in adults. Children with familial hyperlipidemias often have very high lipid levels, and in the great majority, fat-and cholesterol-restricted dietary therapy alone is insufficient to lower levels into the desired target range. Drug treatment with the bile acid-binding resins also does not sufficiently lower levels, and is associated with poor acceptability and compliance, especially in children (1-3). The use of the HMG CoA reductase inhibitors, or statins, is controversial in children, related to concerns regarding long-term safety, cost-effectiveness, and efficacy in terms of reducing clinical disease or events, although there are now several studies documenting effectiveness in lipid lowering and short-term safety (4 -7). Given the long-term nature of therapy, compliance is one central issue. Also, there are no published data regarding short-term safety and effectiveness of combination drug therapy in hyperlipidemic children.We sought to determine whether a low-dose combination of a bile acid-binding resin (colestipol) with pravastatin would result in improved acceptability, compliance, and short-term effectiveness in lipid lowering compared with conventional therapy with a higher dose of colestipol only, with fewer side effects. We also sought to determine short-term safety and effectiveness of combination drug thera...