Short-Term Efficacy and Safety of Pravastatin in 72 Children with Familial Hypercholesterolemia

Knipscheer, H.C.; Boelen, C; Kastelein, John J.P.; Diermen, D.E. van; Groenemeijer, Björn E.; Ende, A. van den; Büller, Harry R.; Bakker, Henk D.

doi:10.1203/00006450-199605000-00021

Cited by 142 publications

(89 citation statements)

References 17 publications

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“…Only nine of the 36 patients in our study had initial baseline LDL cholesterol levels that would be decreased to below 4.1 mM/L if a 25% reduction could be achieved. In addition, the lesser degree of LDL lowering observed with pravastatin in our study compared with that reported by Knipscheer et al (5) probably represents the higher initial LDL levels in our population, and the effects of diminished compliance probably attributable to the concomitant use of colestipol. Hennermann et al (26) studied the effects of diet and drug therapy in 71 children with familial hypercholesterolemia, and although noting significant effectiveness, the vast majority continued to have important hyperlipidemia.…”

Section: Discussioncontrasting

confidence: 55%

A Randomized Crossover Trial of Combination Pharmacologic Therapy in Children with Familial Hyperlipidemia

McCRINDLE

2002

Pediatric Research

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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...

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Section: Discussioncontrasting

confidence: 55%

A Randomized Crossover Trial of Combination Pharmacologic Therapy in Children with Familial Hyperlipidemia

McCRINDLE

2002

Pediatric Research

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“…11,17,19,21 One study showed less patients with adverse events in the statin-treated group, 17 whereas the others did not find a significant difference in the occurrence of adverse events. Analysis of the pooled data revealed no increased risk of an adverse event when receiving statin therapy, as shown by a relative risk (RR) of 0.99 (95% CI: 0.79 to 1.25; Table 3).…”

Section: Safetymentioning

confidence: 99%

“…11,17,20,21 Discontinuations varied from 0% 17 to 9% 20 in the statin groups and 0% 17 to 25% 20 in the placebo groups ( Table 1).…”

Section: Description Of Studiesmentioning

confidence: 99%

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A Systematic Review and Meta-Analysis of Statin Therapy in Children With Familial Hypercholesterolemia

Avis

Vissers²,

Stein³

et al. 2007

ATVB

215

142

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Objective-Functional and morphological changes of the arterial wall already present in young children with heterozygous familial hypercholesterolemia (HeFH) suggest that treatment should be initiated early in life to prevent premature atherosclerotic cardiovascular disease. The purpose of this study was to assess the efficacy and particularly safety of statin therapy in children with HeFH. Methods and Results-We performed a meta-analysis of randomized, double-blind, placebo-controlled trials evaluating statin therapy in children aged 8 to 18 years with HeFH. Six studies (nϭ798 children) with 12 to 104 weeks of treatment were included. Total cholesterol, LDL cholesterol, and apolipoprotein B were significantly reduced, whereas HDL cholesterol and apolipoprotein A1 were significantly increased by statin therapy. No statistically significant differences were found between statin-and placebo-treated children with respect to the occurrence of adverse events (RR 0.

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“…[60][61][62][63][64][65][66][67] Although these studies have generally been short-term, they have shown statins to be safe and effective in lowering cholesterol concentrations. More recent studies have included measures of vascular structure and function.…”

Section: -Hydroxy-3-methyl-glutaryl Coenzyme a Reductase Inhibitors mentioning

confidence: 99%

Lipid Screening and Cardiovascular Health in Childhood

Daniels¹,

Greer²

2008

Pediatrics

1,032

765

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This clinical report replaces the 1998 policy statement from the American Academy of Pediatrics on cholesterol in childhood, which has been retired. This report has taken on new urgency given the current epidemic of childhood obesity with the subsequent increasing risk of type 2 diabetes mellitus, hypertension, and cardiovascular disease in older children and adults. The approach to screening children and adolescents with a fasting lipid profile remains a targeted approach. Overweight children belong to a special risk category of children and are in need of cholesterol screening regardless of family history or other risk factors. This report reemphasizes the need for prevention of cardiovascular disease by following Dietary Guidelines for Americans and increasing physical activity and also includes a review of the pharmacologic agents and indications for treating dyslipidemia in children. Pediatrics 2008;122:198-208 INTRODUCTION Cardiovascular disease (CVD) is the leading cause of death and morbidity in the United States. 1 Most of the clinical burden of CVD occurs in adulthood. However, research over the last 40 years has increasingly indicated that the process of atherosclerotic CVD begins early in life and is progressive throughout the life span. 2 It has also become clear that there is an important genetic component to the disease process that produces susceptibility but that environmental factors, such as diet and physical activity, are equally important in determining the course of the disease process.This statement replaces the outdated 1998 American Academy of Pediatrics (AAP) policy statement "Cholesterol in Childhood," which has been retired. 3 New data emphasize the negative effects of excess dietary intake of saturated and trans fats and cholesterol as well as the effect of carbohydrate intake, the obesity epidemic, the metabolic/insulin-resistance syndrome, and the decreased level of physical activity and fitness on the risk of adult-onset CVD. In addition, more data are now available on the safety and efficiency of pharmacologic agents used to treat dyslipidemia. Most of these data were not available at the time of the previous statement.A number of studies have identified potential risk factors for adult CVD. 4 The strongest risk factors include a high concentration of low-density lipoprotein (LDL), a low concentration of high-density lipoprotein (HDL), elevated blood pressure, type 1 or 2 diabetes mellitus, cigarette smoking, and obesity. Research in children and adolescents has demonstrated that some of these risk factors may be present at a young age, 5 and pediatricians must initiate the lifelong approach to prevention of CVD in their patients. The focus of this report is on improving lipid and lipoprotein concentrations during childhood and adolescence to lower the lifelong risk of CVD. The current obesity epidemic among children has increased the need for pediatric health care professionals to be knowledgeable of the risk factors for CVD and to implement the changes recommended in...

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Short-Term Efficacy and Safety of Pravastatin in 72 Children with Familial Hypercholesterolemia

Cited by 142 publications

References 17 publications

A Randomized Crossover Trial of Combination Pharmacologic Therapy in Children with Familial Hyperlipidemia

A Randomized Crossover Trial of Combination Pharmacologic Therapy in Children with Familial Hyperlipidemia

A Systematic Review and Meta-Analysis of Statin Therapy in Children With Familial Hypercholesterolemia

Lipid Screening and Cardiovascular Health in Childhood

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