Effect of Rosuvastatin on Carotid IMT in HeFH Children

Study Questions:

What is impact of rosuvastatin on carotid intima-media thickness (IMT) in children with heterozygous familial hypercholesterolemia (HeFH)?

Methods:

A multicenter, prospective, open-label study was performed using siblings of HeFH patients as controls. Children with HeFH aged 6 to <18 years and low-density lipoprotein cholesterol (LDL-C) >4.9 mmol/L (>190 mg/dl) or LDL-C >4.1 mmol/L (>158 mg/dl) in the setting of additional risk factors received rosuvastatin for 2 years. The starting dose was 5 mg once daily, which was escalated to 10 mg for patients aged 6 to <10 years or 20 mg for patients aged 10 to <18 years. Carotid IMT was assessed by ultrasonography at baseline, 12, and 24 months in all patients and in age-matched unaffected siblings. P-values of carotid IM measurements were adjusted for age, sex, carotid artery site, and family relations.

Results:

At baseline, mean carotid IMT was significantly greater for the 197 HeFH children (0.397 ± 0.049 mm) as compared with the 65 unaffected siblings (0.377 ± 0.045 mm, p = 0.001). During 2 years of follow-up, mean reduction in LDL-C was 41% (2.4 mmol/L [93 mg/dl]) and 38% of patients achieved the goal of <2.85 mmol/L (110 mg/dl). The rate of change in carotid IMT was lower in the HeFH patients as compared with controls (p = 0.002). The end-of-study difference in mean carotid IMT between HeFH children and unaffected siblings after 2 years was no longer significant (0.408 ± 0.043 mm and 0.402 ± 0.042 mm, respectively, p = 0.2).

Conclusions:

Baseline carotid IMT was significantly greater in patients with HeFH as compared with unaffected siblings. Treatment with rosuvastatin resulted in a slower increase in carotid IMT in HeFH children than untreated unaffected siblings.

Perspective:

This study assessed the impact of rosuvastatin on carotid IMT in children with HeFH. The study demonstrated both a significant reduction in LDL-C as well as rate in change of mean carotid IMT in patients as compared with unaffected, untreated siblings. The primary limitation of the study is a lack of a true placebo control group with double-blind randomization. It was not thought to be ethical to withhold therapy with a statin in this patient population. Although statin therapy has been shown to be effective in both lowering LDL-C levels as well as slowing the rate of increase in carotid IMT, there is as of yet no firm evidence that treatment with lipid-lowering agents prevents cardiovascular events later in life. Despite this, existing data support early initiation of LDL-C reduction in children with HeFH.

Clinical Topics: Congenital Heart Disease and Pediatric Cardiology, Diabetes and Cardiometabolic Disease, Dyslipidemia, Noninvasive Imaging, Prevention, Congenital Heart Disease, CHD & Pediatrics and Arrhythmias, CHD & Pediatrics and Imaging, CHD & Pediatrics and Prevention, CHD & Pediatrics and Quality Improvement, Homozygous Familial Hypercholesterolemia, Lipid Metabolism, Nonstatins, Novel Agents, Primary Hyperlipidemia, Statins, Echocardiography/Ultrasound

Keywords: Carotid Intima-Media Thickness, Cholesterol, LDL, Dyslipidemias, Heart Defects, Congenital, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hypercholesterolemia, Hyperlipoproteinemia Type II, Hypolipidemic Agents, Primary Prevention, Risk Factors, Siblings


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