20-Year Follow-up of Statins in Children

A recent study (IK Luirink et al. NEJM 2019; 381: 1547-56) examined the effects of statin therapy in children with familial hypercholesterolemia (FH) who were followed for 20 years. At baseline, the median age was 13 years in the treated cohort and in their sibling control group.  184 of 214 (86%) of patients with FH were seen in follow-up and 77 of 95 (81%) of siblings.

Key findings:

  • The mean LDL cholesterol had decreased from 237 to 161 mg/dL
  • LDL target of <100 mg/dL was achieved in 37 patients (20%)
  • Mean progression of carotid intima-media thickness over the entire follow-up period was 0.0056 mm/year in patients with FH and 0.0057 mm/year in sibling controls
  • The cumulative incidence of cardiovascular events and death from cardiovascular causes at age 39 years was lower in the treated group compared to  their affected parents: 1% vs. 26% and 0% vs. 7% respectively


“This makes a strong case for not only ‘the lower the better’ but also for ‘the younger the better” as atherosclerotic disease is determined not only by the LDL level but also by cumulative exposure.

My take: This study provides convincing data that statin therapy prolongs health and life in patients with familial hypercholesterolemia.

Related blog posts:

Are Liver Tests Needed in Pediatric Patients Receiving Statin Therapy?

A recent study (NK Desai et al. JPGN 2019; 68: 175-81) showed excellent safety of statins with regard to hepatotoxicity. This study utilized prospectively collected ALT values from the Preventive Cardiology Program at Boston Children’s and their lipid program from 2010 until 2014.  They included 943 patients (mean age 14 years) with 111 always on statin, 97 started on statin, and 735 never on a statin.

Key findings:

  • In this cohort with dyslipidemia, there was no higher burden of ALT elevations among pediatric patients receiving statin therapy compared to those who did not receive statin therapy.
  • Patients with ALT values ≥5 times ULN were not increased among patients receiving statins (n=3) compared to those who did not receiving statins (n=13)
  • Mean ALT was actually greater in the non-statin cohort by 2 U/L but likely related to the increased frequency of obesity in the non-statin group.

My take: Due to the high prevalence of nonalcoholic fatty liver disease (NAFLD), it is likely that most patients who need statin therapy would get liver biochemistries; however, this study suggests that additional monitoring is not required in asymptomatic patients who receive statins for dyslipidemia.

Related blog posts:

Georgia Aquarium

Treatment Outcomes in Children and Adolescents with Hypercholesterolemia

A recent study (MM Mendelson et al. J Pediatr 2016; 178: 149-55) provides some useful data indicating that statin therapy for children and adolescents is typically effective based on cholesterol reduction levels.

This observational study prospectively collected data from 2010-2014 among 1521 pediatric patients seen for a lipid disorder.  In this cohort, 1260 patients (83%) did not receive statin therapy during the study period.  Ultimately, 97 patients (6% of clinic cohort) had received statin therapy and had adequate data for evaluation.

  • 70 patients received simvastatin: 1 at 5 mg/day, 26 at 10 mg/day, and 43 for 20 mg/day.
  • 24 patients received atorvastatin: 22 at 10 mg/day and 2 at 20 mg/day
  • 3 patients received pravastatin: 2 at 10 mg/day and 1 at 20 mg/day

Primary outcome for therapy: LDL-C <130 for patients without high risk factors and <110 for patients with high risk condition(s) (eg. diabetes mellitus, end-stage renal disease, heart transplant, Kawasaki disease with aneurysms)

Key findings:

  • Median baseline LDL-C was 215.
  • LDL-C decreased by 37% on average (83 mg/dL) within the first 60 days of therapy
  • Achieved primary outcome: 60% at 1 year,  73% at 2 years, and 87% at 3 years
  • No patients presented with relevant hepatic or myopathic side effects. 2 of 97 had transient epiosde of ALT > 3 x ULN.


  • Overall, the reported outcomes in this select cohort were at least as good as outcomes reported in studies of adults in the general population.  This may be due to parental supervision or perhaps due to a better physiologic response. In addition, as this was an observational study, poorly adherent patients may be lost to follow-up and would not be accounted for.
  • Currently statin therapy is recommended if lifestyle modifications are not sufficient to lower LDL-C.  Thus, “it is estimated that more than 700,000 US children and adolescents may be eligible for statin therapy according to the 2011 NHLBI guidelines.”

My take: Since cholesterol and LDL-C are biomarkers of treatment, the long-term benefit (& possible risks) of statin therapy remains unclear .  However, more data on meaningful endpoints like heart attacks and strokes could take decades.  Until then, the best evidence available suggests that the potential benefit of statin therapy could be quite substantial.

Related posts:


Cholesterol controversy

Recent guidelines (Pediatrics 2012; 130: 353-56) have recommended universal screening for hypercholesterolemia between ages 9-11 along with additional targeted screening.  These recommendations have been met with a number of criticisms (Pediatrics 2012; 130: 349-52).

In the first referenced commentary, the experts who issued the guidelines commissioned by the National Heart Lung and Blood Institute (NHBLI) claim that the criticism “misrepresent the evidence regarding screening and the specificity and rigor of the guideline development.”  In the second commentary, the guidelines are considered overly aggressive and not adequately founded on evidence-based medicine.  In addition, they cite two JAMA commentaries that also question the wisdom of the guidelines (JAMA 2012; 307: 257-58, & 259-60).

NHBLI recommendations:

▪  Universal screening of all 9-11 year-olds with a nonfasting lipid panel.

▪  Targeted screening of 2-8 year-olds and 12-16 year-olds with 2 fasting lipid profiles.  The targeted group are for those with diabetes, hypertension, BMI >95%, smoke cigarettes, have a parent with cholesterol >240 (or known dyslipidemia), 1st or 2nd degree relative (includes parents, aunts, uncles, and grandparents) with stroke or coronary artery disease <55 years for men or <65 for women.  According to the critical commentary, 30-40% of children will meet family history criteria and many more will meet other criteria.

▪  If LDL ≥130 mg/dL, then a “CHILD-1” diet is recommended.

▪  Individuals with abnormal screening are to have fasting lipid panels every 6-12 months indefinitely even if their values become acceptable.

Criticisms and responses by guideline authors in italics

▪  While the critics concede that cumulative exposure to high LDL and hypertension increase the risk of cardiovascular disease (CVD), they indicate that with the exception of a small number of individuals (rare homozygous familial hypercholesterolemia) that there is not proof that intervention in childhood is necessary.  The chain of evidence cited by the panel has “notably the absence of even observational evidence or modeling to estimate the clinical event benefits of screening for and intervening on these risk factors in children.”  Atherosclerosis is a lifelong process…Heterozygous familial hypercholesterolemia affects 1:500 and 51% of untreated men develop CV disease events by age 50 years… Accidental death studies (ages 15-30 years) have shown that a 30 mg/dL increase in non-HDL was equivalent to 2 years of vascular aging.  Bogalusa Heart Study showed that number of risk factors correlated with increased atherosclerosis at autopsy after accidental death.  Carotid intima media thickness in adulthood correlates with LDL levels obtained between 12-18 years of age.

▪  No quantification of potential harms such as neuroses, family conflict, CVD anxiety or from medication.  Among children with familial cardiovascular disease, interview studies have shown positive future health perceptions and effective coping.  ‘A study of universal CV risk screening in schools, accompanied by environmental change, showed improvements in healthy lifestyle behaviors and CV risk profiles.’  Risk of statin therapy, (only 0.8% of adolescents would be eligible per authors) has shown no adverse effects in children and adolescents.

The majority of the panel members…disclosed an extensive assortment of financial relationships with companies making lipid-lowering drugs and lipid-testing instruments.  Evidence regarding the efficacy and safety of these medications would not be available without academic partnership with industry.  Potential conflicts of interest were declared and vetted.

▪  Cost/cost-effectiveness. The present policy proposes an intervention applied to a healthy and asymptomatic population, with an enormous impact on costs and the potential to transform well children into patients with a chronic disease label. “Any intervention with nonzero benefit may be recommended, regardless of how much it costs and how much better health might be achieved by investing those resources elsewhere.”  There have been several studies exploring the cost-effectiveness of screening and management strategies for familial hypercholesterolemia (FH). In the Netherlands, a genetic screening program showed that new cases of FH gained 3.3 years of life at an average lifetime cost of US$8700 per year gained.  More complex cost-effectiveness modeling of treatment of children and adolescents has not yet been performed.

So who is right in this debate?

Previous related blog entry:

Cardiovascular disease for the entire family