In the past few years there's been a steady push to get kids with very high cholesterol on statins, the LDL-lowering drugs already found in the medicine cabinets of 13 million Americans. Now the American Academy of Pediatrics—the nation's most influential group of pediatricians—has gotten in on the act. On Monday, it released new guidelines suggesting that docs should start testing overweight kids or those with a family history of heart disease for high cholesterol at age 2—and that they should consider prescribing statins as early as age 8. Four of the drugs are already FDA-approved for use in kids. The new AAP recommendations are sure to be controversial, especially since the drugs' long-term effects on kids are unknown. Newsweek's Mary Carmichael spoke with Peter Belamarich, a pediatrician at Children's Hospital at Montefiore Medical Center in New York City, who has prescribed statins to some kids but takes issue with the new guidelines. Excerpts:
NEWSWEEK: You've written that "lifestyle modification is the cornerstone of cardiovascular prevention in childhood." Isn't that what the AAP should be focusing on? Are you worried that these guidelines will encourage doctors to prescribe drugs to kids with high cholesterol instead of changes in diet and exercise?
Peter Belamarich: No. If people read them carefully, they say that the statin medications should be targeted to very high-risk children. The kids who would qualify for drug treatment based on these guidelines are less than 1 percent of all children. Ninety-nine percent of children and adolescents still should be treated with what's called therapeutic lifestyle change: limiting animal fat, increasing physical activity to an hour a day.
So what is your problem with the AAP guidelines?
My criteria for what justifies medication are higher than the guidelines'. I tend not to start medication until after age 10. And I don't treat very high-risk girls as aggressively as I would treat very high-risk boys, for two reasons: One, women develop cardiovascular disease slightly later in life, so there's less urgency in initiating treatment in childhood. Two, there are data suggesting that statins can interfere with growth and development in utero, so we should not use them in anybody who might get pregnant unintentionally, and that would include adolescents.
What does "very high-risk" mean regarding children and heart disease? It's not like these kids are having heart attacks at 10.
I think the children who most deserve these meds, if anybody does, are children who have a direct family history of premature coronary heart disease in young relatives who are under 40 or 50. Often, those kids have very low HDL, or "good," cholesterol levels. So I tend to treat boys with low HDL, a positive family history and "bad" LDL levels in the 190s [milligrams per deciliter]. What makes it tricky is that prescribing these drugs in kids requires a lot more clinical judgment than it does in adults. In adults, there are scores that put all the risk factors together—hypertension, age, smoking, diabetes, sex, LDL/HDL ratio—and in middle-aged men, you can predict the risk of heart attack in the following year using those scores. We don't have that kind of score for children. So we have to use our judgment.
Are there enough data to support the use of statins in kids?
There's unequivocal data that if you've had a heart attack, you should be on statins. There's no question, this is a fantastic drug. It decreases your risk of another heart attack by 30 percent or more and it's very safe. But that's for middle-aged people at high risk. We need studies with a logical progression showing it's OK to treat young adults, then very high-risk adolescents and then extremely high-risk children younger than that. And that data is not all there. Some people would say, "Look, we're in the midst of an epidemic and it's really unethical to wait to start treatment." And other people, such as myself, would say that we need to be absolutely sure that what we're doing is safe before we do it.
Statins do have side effects in adults. Should we be worried about any of these with kids?
Oh, absolutely. Anybody who's prescribing these drugs should be aware and trained in their use. The two most common side effects are muscle effects—they can cause muscle cell destruction, which would manifest as weakness and muscle aches—and hepatitis, or an elevation of liver cell enzymes and liver damage. For the majority of adults, those are dose-related effects. The FDA did only approve lower doses for children, so [kids] are probably at decreased risk for those effects. But all of our thresholds for these effects should be less in childhood.
In adults, statins lower cholesterol, but they also make plaque less unstable, so it doesn't break off and cause a heart attack. Is that right?
Statins have other effects than lowering lipid levels. What they don't do in high-risk adults is make atherosclerosis go away. That's been confirmed in a number of studies. So the question is, how do they work? If they don't make the plaque disappear, what are they doing? They're doing something to diminish the risk that the plaque would rupture or erode or bleed.
But kids don't usually have that kind of high-risk unstable plaque.
We're asking statins to do something different in kids—we're asking statins to retard the progression or development of plaque. In other words, we're asking the drug to do something it hasn't been shown to do in adults. There are some studies in adolescents with familial hypercholesterolemia [a rare, inherited form of extremely high cholesterol] that use ultrasound of the carotid artery to show that statins prevent the thickening of the carotid artery.
What exactly is the link between high cholesterol in childhood and risk of heart disease later on?
I don't think we're at the point of looking at a child and being able to predict the risk of coronary heart disease with great certainty. What we do know is that there's a lot of evidence that links childhood risk factors with future risk. There's epidemiological evidence that heart attack risk in adulthood is related to children's cholesterol levels in a population. The societies with the highest risk of heart disease tend to be the societies where the children in that population have high serum levels.
I'm assuming the U.S. is right at the top?
We're somewhere in the middle, actually. Then if you take adults who have had heart attacks, their children tend to have high cholesterol. And in autopsy studies of kids who died in accidents, they've found that in adolescents, just like in adults, there's a link between the numbers for cholesterol levels and the amount of plaque in the arteries.
You wrote last year in
that "the results of adult statin studies are so striking and favorable that one is tempted to generalize them to children, adolescents and adults at low risk; however, there are important caveats in the extrapolation of these results to children." What are those caveats?
The short-term safety studies in children are very reassuring, but what we don't know and need to study is whether statins have unique long-term effects on developing organisms. We don't know about that yet. The statin trials have been too short to say one way or the other. That's why we have to be cautious about translating their broad use. … Now, there's an argument that you do have to take risks to make progress in medicine. But those risks have to be very carefully calculated. We need to create a registry of children treated with statins, or obligate the pharmaceutical industry to do so, or else we have to have a large federally funded study, because the current way we monitor these children for long-term effects isn't adequate. The problem is that the timeline for any study is just so long that no one has conceived of a way of creating one.
You'd have to follow kids for 50 years.
Exactly. This kind of data will probably eventually emerge from electronic health databases, but it will not be a randomized controlled trial.
paper noted that "patients begun on a statin during adolescence will receive a cumulative dose that far exceeds that which most adults have received." If kids do go on these drugs, can they ever go off? Or are they basically going to be on the drugs for life?
It's an interesting question. One would hope that if you're talking about a kid who is overweight, that can change—the kid could lose weight and come off the drugs. In the future, we'll also probably be able to do non-invasive imaging of the arteries.
So docs could look at kids' arteries directly and say, "You're done."
Right: "You need to take a drug holiday for a while." I tell my patients it will be about five years before we have that kind of imaging. Once we have it, it'll be easier to make a case for treating some kids. But right now, treating risk factors without knowing about the kids' arteries is less than ideal.
Do you think that eventually statins could be used broadly in kids—not just the 1 percent but a larger group?
It's too soon to say. Our first obligation is to address a public health crisis. Part of the issue with these guidelines is that the problem has its roots in the obesity epidemic. It's not that obesity raises cholesterol that much, but it's a complicating factor—it would push a child with high cholesterol into a higher-risk group. What we should be focusing on is collectively addressing the problem we've created for our children. They're overweight and they're going to suffer as a consequence. We need to figure out how to help them in the school system and with after-school programs. Everybody can play a role in that, not just doctors and drug companies.