Statins May Benefit Kids With Recalcitrant Lipids

According to 1992 national guidelines on cholesterol, children and adolescents with abnormal lipids should follow a fat-and cholesterol-restricted diet aimed at normalizing lipid values over 6–12 months.¹ But what if such dietary management fails to sufficiently improve their lipid profiles? Physicians should consider prescribing statins for these young people if they have familial hypercholesterolemia, suggests a new American Heart Association (AHA) statement.²

Brian W. McCrindle, MD, MPH, senior scientist with Child Health Evaluative Sciences and staff cardiologist at The Hospital for Sick Children, both affiliated with University of Toronto, and colleagues arrived at this recommendation after assessing results from clinical trials in children and adolescents with familial hypercholesterolemia as well as from statin studies in adults. They also factored in evidence indicating that atherosclerosis begins during childhood.

Data supporting the AHA recommendations have emerged since the 1992 release of the National Cholesterol Education Program (NCEP) Expert Panel on Blood Cholesterol Levels in Children and Adolescents.² NCEP recommends bile acid-binding resins, such as cholestyramine (Questran, Bristol-Myers Squibb), colestipol (Colestid, Pfizer), and colesevelam (WelChol, Sankyo), as the initial drug for children ≥10 years (or after menarche for girls) who require lipid-lowering drug therapy.²

Yet, McCrindle says, “It is well documented that the resins are very poorly tolerated, with very poor compliance in children.” Furthermore, bile acid-binding resins don't lower lipids enough to significantly reduce children's lipid profiles.^2,3

In comparison, statins appear to more effectively lower total and LDL cholesterol in children with familial hypercholesterolemia.³ But the idea of initiating statin therapy in children may give some clinicians pause: The drug has been associated with elevated liver enzymes and increased creatine kinase (CK) levels, and these drugs would be instituted at a young age, presumably for lifelong therapy, says Robert H. Eckel, MD, professor of medicine at University of Colorado at Denver and Health Sciences Center and director of University Hospital's Lipid Clinic. (Eckel, a past president of AHA, notes that he had no role in the development of these AHA guidelines.)

“The evidence is good to indicate that statins are safe over short intervals,” Eckel says. “The concerns relate to potential downside effects that might occur decades later.”

EARly lIpIDS SCREENING

Step one is to identify those children needing lipids intervention. NCEP suggests selective lipids screening for children and adolescents with a family history of early coronary heart disease or high cholesterol.^1–3 But screening based on family history may miss 30–60% of young patients with elevated lipids, according to a recent evidence synthesis by the Agency for Healthcare Research and Quality.³

The AHA modifications place a greater emphasis on assessing cardiometabolic risk. For instance, a child with obesity should undergo lipids screening regardless of family history, McCrindle says.

And, in spite of reservations about prescribing statins to youth, Eckel acknowledges the importance of early identification of cardiovascular risk. “We know atherosclerosis does occur in young people.”

In addition to plotting height and weight, calculating body mass index (BMI), and taking family history as part of well-child care, McCrindle suggests that primary care physicians also plot BMI and update family history over time—then use all these factors to decide how aggressively to address elevated lipids.

“A lot of overweight kids will have lipid abnormalities,” McCrindle says, “but not to the magnitude that will require drug therapy.”

IMAGE SOURCE/PUNCHSTOCK

WHEN TO USE STATINS

McCrindle's group does not advocate widespread use of medications to treat lipid abnormalities associated with childhood obesity.²

“The bar is set rather high, so the vast majority of [young] people who meet the criteria for starting drugs will have familial hypercholesterolemia,” McCrindle says. The incidence of familial hypercholesterolemia in the U.S., Canada, and Europe is 1 in 500.³

Clinicians considering drug therapy in dyslipidemic children should follow NCEP criteria for drug initiation (see chart), AHA recommends. Additionally, the new AHA recommendations call for clinicians to:

1. Ensure that patients and families understand potential adverse effects (especially myopathy), drug interactions (involving cyclosporine, fibric acid derivatives, niacin, erythromycin, azole antifungals, nefazodone, and many HIV protease inhibitors), and pregnancy contraindications and contraception needs.

2. Assess baseline CK, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) measurements.

3. Initiate the lowest dose (once daily at bedtime) of the statin of choice.

4. After 4 weeks, compare fasting lipoprotein, CK, ALT, and AST measures with baseline values. Continue therapy if patients obtain target LDL cholesterol levels with no abnormal laboratory values. Reassess at 8 weeks and 3 months.

Patients with laboratory abnormalities or adverse reactions should cease therapy until parameters return to normal. Among patients with no adverse reactions or abnormal laboratory values who have not achieved target LDL cholesterol levels, clinicians may double the statin dosage, with monitoring, and may continue adjusting the dosage until the patient achieves the target LDL or shows evidence of toxicity.

McCrindle and his colleagues suggest recommendations for statin therapy, such as these, be subject to ongoing study and modification. ▪

Diet Advice Makes a Difference

Ideally, children at risk for diet-related medical problems should see a registered dietitian for assessment of eating patterns, says Roberta H. Anding, RD, American Dietetic Association spokesperson and pediatric dietitian at Texas Children's Hospital in Houston.

But, Anding notes, in 5 minutes a busy physician can suggest dietary changes to help children lower their lipid levels:

1. Eat low-fat dairy. Since most children get saturated fat and cholesterol from dairy products, changing from whole milk to 1%, 1/2%, or skim milk and choosing reduced-fat cheeses will cumulatively lower saturated fat and cholesterol intake over time.

2. Avoid refined flours and grains, such as white bread, white tortillas, and white rice.

3. Cut out sweet drinks, such as diet and regular soft drinks, fruit punch, lemonade, and sweet tea. Reserve sports drinks for participation in athletics.