Statins Started in Kids With FH Provide Benefits in Adulthood

Twenty-year data should put to rest concerns over the long-term safety of statins in children with familial hypercholesterolemia.

Statins Started in Kids With FH Provide Benefits in Adulthood

Starting statins during childhood in people with familial hypercholesterolemia (FH) safely slows the progression of carotid intima-media thickness and reduces the risk of cardiovascular disease events in adulthood, according to 20-year follow-up on patients previously enrolled in a randomized controlled trial.

“There's no reason anymore to withhold drug therapy in these kids,” study co-author John J.P. Kastelein, MD, PhD (Amsterdam University Medical Centers, the Netherlands), told TCTMD. He explained that over the years many physicians have been reluctant to prescribe statins to children given the drugs’ unknown effects on grown and development, although the American Academy of Pediatrics has supported the use of statins in children with FH age 8 or older despite a lack of evidence.

“[Our study] will make it much easier for physicians to prescribe statins to kids with elevated cholesterol, and it will also reinforce the message that it's at least as important to start early than to treat aggressively [later],” Kastelein added.

The original study had compared a statin versus placebo for 2 years, after which the trial ended and participants stayed on statins. Then, approximately 20 years later, investigators reached out to all patients as well as their siblings without FH to see what had happened in the ensuing years.

“This is a paper I've been waiting for for a long time,” Sarah de Ferranti, MD (Boston Children's Hospital, MA), who was not involved in the study, commented to TCTMD. “In an ideal world, we would examine whether children treated with statins benefit in terms of reducing their risk of heart disease events. We would take a group of kids with what looks like familial hypercholesterolemia and we would follow them for 30-40 years, and we'd take half the group and put them on a statin at an early age and then see if that made a difference in terms of their rate of heart attack. But people don't generally want to be in a randomized controlled trial for 30 years and so we don't have any data like that, or we haven't.”

Previous observational studies have demonstrated that a diagnosis of FH is associated with carotid artery changes, a likely proxy for the coronary arteries, de Ferranti explained, “but it hasn't been the real deal. So this report really gives us information about these kids and what happens to them decades later.”

The findings were published in the October 17, 2019, issue of the New England Journal of Medicine.

Long-term Benefit

For the study, Kastelein along with lead author Ilse Luirink, MD (Amsterdam University Medical Centers, the Netherlands), and colleagues collected 20-year follow-up data from 184 of 214 FH patients enrolled in a randomized trial comparing pravastatin and placebo between age 8 and 18 and 77 of their unaffected siblings. All children had been genetically tested for FH and cardiovascular event data from the affected parents were also collected. After the 2-year trial period, all children were continued on pravastatin.

This report really gives us information about these kids and what happens to them decades later. Sarah de Ferranti

At follow up, 79% of the FH patients said they were currently using a lipid-lowering medication and 84% of those said they had taken 80% or more of their prescribed medication over the past month. The mean LDL-cholesterol levels of the FH patients had decreased 32% from baseline (237.3 to 160.7 mg/dL) and 20% of patients had achieved an LDL < 100 mg/dL treatment goal. Also, the mean progression of carotid intima-media thickness in the FH patients was 0.0056 mm/year compared with 0.0057 in their unaffected siblings (mean difference adjusted for sex -0.0001 mm/year; 95% CI -0.001 to 0.0008).

Compared with their affected parents, the FH patients enrolled in the study saw a lower cumulative incidence of cardiovascular events (1% vs 26%) and cardiovascular death (0 vs 7%) at 39 years old.

As for safety of statins in the FH patients, Kastelein said “we measured everything we could under the sun—they have normal maturation, normal height, normal hormones. They've no liver problems, actually nothing, and in fact they are better off than their parents because none of them died from a heart attack [by age 39], while quite a number of their parents had severe heart attacks and strokes. So in the end, everything panned out well.”

More Comfort With Statins

de Ferranti said that while she had expected to see good safety with statins over the long-term in these FH patients, “it is reasonable to be worried about taking a medicine for a long time regardless of your age or what the medicine is. That's something that we should think about, which is why we don't use statins in children with mild lipid disorders and we reserve them for those individuals who we really think have a high risk of premature cardiovascular disease events like individuals with familial hypercholesterolemia.”

Because of the size of the study, the results likely do not provide “enough information to eliminate the possibility of rare long-term side effects of statins, . . . but we do know from adult studies with tens of thousands of people taking statins for decades that those people who take statins actually live longer than those people who don't,” she continued. “That's reassuring in some ways, even though it's not pediatric populations. It seems like if there was something, we might have seen it in that patient population.”

The study should not inform a change in practice with regard to current guidelines, de Ferranti argued, acknowledging, however, that “what is recommended by guidelines and what is implemented differs, and it differs particularly in this field.” For example, FH screening is recommended beginning at age 2 in patients with a concerning family history, but many children are never screened and those screened often don’t receive statins.

“Part of the barrier to implementing that more broadly from pediatricians may be that they are worried about the safety and benefits of statins,” she said, adding that pediatricians can now find reassurance in this study about giving statins when lifestyle changes don’t suffice.

de Ferranti also stressed the importance of viewing FH as a genetic disease much like cystic fibrosis or Down Syndrome in that these patients, above individuals with milder lipid abnormalities, need statins to prevent adverse events. “All high cholesterol is not the same and this genetic [component] really needs to be considered in a different light,” she said. “Familial hypercholesterolemia is a genetic disease. . . . As we better understand that, we become more comfortable with the fact that a few kids might require medicine to treat this very preventable cause of early heart attack.”

  • The study was supported by a grant from the AMC Foundation.
  • Kastelein reports receiving personal fees from Amgen, CSL-Behring, Esperion, Gemphire, Madrigal, Medicines Company, AstraZeneca/Omthera, Staten Biotech, and Regeneron.
  • Luirink and de Ferranti report no relevant conflicts of interest.