Kids and Statins: Medical Management

22 Feb
2010

Kids

Certainly in adult medicine, persistent dyslipidemia may be countered with the addition of cholesterol-lowering drugs. Also, intrinsic to the decision to prescribe medications is a consideration of comorbidities such as diabetes, obesity, smoking, hypertension, along with knowledge of the patient’s pre-existing cardiovascular or peripheral vascular disease. Aside from the growing predisposition toward obesity, children rarely exhibit the same comorbidities that afflict the adult population.

This being said, the incidence of type-2 diabetes mellitus and of the poorly defined metabolic syndrome is skyrocketing in obese older children and adolescents and is becoming a recognized comorbidity in this population. The syndrome is not well defined in children; it is an evolving diagnosis, and it perceived by many to be a future problem. Children with truncal obesity, elevated triglyceride levels, and insulin resistance have the syndrome, but we don’t know what constitutes significant enough truncal obesity and insulin resistance for a child to receive the diagnosis. We cannot use the adult woman’s “35-inch waist” and the adult man’s “40-inch waist” as criteria.
Much of the data on the efficacy of statin drugs in terms of cardiovascular morbidity and mortality exists in secondary prevention studies (i.e., in patients with already established coro­nary artery disease). However, on the basis of limited primary prevention analyses in adult medicine, the consensus is that cholesterol-lowering attempts are warranted even in the absence of other risk factors or of pre-existing cardiovascular disease. Furthermore, primary prevention studies have not conclusively determined the desired target goal for lipid levels in younger people. Unfortunately, primary prevention studies involving adults cannot be extrapolated properly to children for whom medical treatment is being considered for primary prevention of cardiovascular disease.

Further confounding the entire matter: although studies of adults reveal reductions in cardiovascular mortality, cholesterol-lowering drugs have not uniformly demonstrated significant reductions in all-cause mortality. Thus, lowering one’s cholesterol level might prevent some forms of heart disease, but some other disease will still get us in the end. It is important to state that there has never been a demonstrated direct causality of statins to noncardiovascular mortality.

This finding thus illustrates the importance of emphasizing the quality—but not necessarily the quantity—of one’s years in terms of disease prevention. Although we are merely speculating, we would think that reducing cardiovascular disease in adults should improve their ability to remain vigorous, active, and content. These are all desirable goals, even though we do not have evidence to conclude that improving cholesterol levels reduces overall mortality. buy generic levitra

After taking all of these facts into account, medical providers may consider medication therapy for children older than 10 years of age. The choice of medication is another challenge.

For a long time, the bile acid-binding resins were the staple of pharmaceutical management in children. These were preferred because of their impressive safety profile; however, poor palatability, significant gastrointestinal side effects, and limited cholesterol-reducing effects made this class of drugs a poor choice.

Along came the statins, which act in the liver to block cholesterol synthesis, thereby resulting in up-regulation of LDL-C receptor expression. This in turn results in more cholesterol-laden LDL particles being pulled out of the blood.

Recent exciting data also suggest a pleiotropic effect of statins as anti-inflammatory agents against atherosclerosis. By acting to inhibit precursor metabolites of cholesterol that trigger inflammation, statins may have a significant vascular protective effect. A growing number of double-blinded, placebo-controlled pediatric studies have demonstrated excellent LDL-C-lowering effects of this class of medications. Safety profiles have been excellent, and reports about possible growth or maturational interference have not been confirmed. Unfortunately, these studies have relatively short-term follow-up periods. canadian antibiotics

Let us revisit the hypothetical adolescent male who is being medically treated with statins. We can assume that he has experienced excellent lowering of LDL-C and total cholesterol levels as well as a modest elevation in high-density lipoprotein-cholesterol (HDL-C). Now additional questions arise:

  • How long do we treat this adolescent with statins?
  • What if there is a significant rise in liver enzymes?
  • What if creatine phosphokinase levels rise significantly after vigorous sporting activities or muscle trauma?

In general, our knowledge about statins in children is based on a few clinical studies that followed children for six months to two years after initiation of the study drug. Approximately 1% to 5% of children show significant increases in liver enzymes, and fewer develop rhabdomyolysis. In most older children and adolescents without underlying liver disease, the elevation of liver enzymes greater than three-fold warrants discontinuing the statin. In a significant majority, enzyme levels return to normal after the medication is stopped. However, the rest of our questions are not yet answered.

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