Statin initiation for girls of childbearing age requires pregnancy planning discussion
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Statin therapy at a young age is safe and effective in preventing future adverse CV events in patients at increased atherosclerotic risk, but girls and women may require counseling for pregnancy planning, a speaker reported.
According to a presentation at the virtual National Lipid Association Scientific Sessions, children and adolescents with elevated risk for atherosclerosis, especially those with familial hypercholesteremia, may benefit from early statin initiation. However, the impact of contraceptive hormonal therapies on lipid levels may require special consideration and shared decision-making for adolescent girls who are considering statin therapy.
The 2018 American Heart Association/American College of Cardiology Guideline on the Management of Blood Cholesterol recommends universal screening of fasting lipid profile or nonfasting HDL in children and adolescents without CV risk factors or family history of early CVD. To detect moderate to severe abnormalities, the guidance recommends lipid evaluation between age 9 and 11 years, and again between age 17 and 21 years.
Per the 2018 guideline, for children and adolescents aged at least 10 years with an LDL persistently greater than 190 mg/dL or higher than 160 mg/dL with a clinical presentation consistent with familial hypercholesterolemia and who do not respond to lifestyle modifications, it may be reasonable to initiate statin therapy.
However, Ann Liebeskind, MD, FNLA, FAAP, faculty member of the NLA Foundations in Lipidology Course and an internist and pediatrician in Neenah, Wisconsin, said, “It is important to realize that they do vary to the approval by age and that there are some different starting doses for children compared to adults.”
Among children and adolescents with a family history of early CVD or significant hypercholesterolemia, providers may consider taking lipid measurements as early as age 2 years to identify potential familial hypercholesterolemia or other rare forms of hypercholesterolemia.
“Cholesterol is an important precursor of adrenal and gonadal steroids, so there was some concern that perhaps this would not be a safe drug for a child,” Liebeskind said in the presentation. “However, we now know that many children with familial hypercholesterolemia have been on statins for decades and have ultimately done very well.”
The presentation referenced a Cochrane review that evaluated nine randomized, placebo-controlled studies that enrolled 1,177 pediatric participants. The review identified no significant difference between statin therapy and placebo with regard to adverse effects, including delayed sexual maturation, liver enzymes, creatine kinase elevation and rhabdomyolysis.
Moreover, among patients assigned to pravastatin, researchers found no major adverse events at 10 years.
“All current guidelines absolutely recommend cautious use of statins in girls of reproductive ages, even though there may be some preliminary data that, for example, in the midtrimester, pravastatin may possibly help reduce preeclampsia in women,” Liebeskind said during the presentation.
Two systematic reviews, published in the Journal of Clinical Lipidology and Expert Review of Cardiovascular Therapy, evaluated the association between statins and teratogenicity. Neither found evidence that statins caused congenital anomalies independent of concomitant medical conditions associated with their use.
“None of this is per guidelines at this time. All guidelines clearly recommend when using statins in females that you avoid pregnancy,” Liebeskind said. “Maybe in the future, some of this evidence will evolve and we’ll feel more comfortable using statins in women of childbearing age who are actively trying to be pregnant or are pregnant. But at this point, it is not the standard of care.”
According to the presentation, for patients with a confirmed receptor defect who are also of childbearing age, clinician-patient discussion of behavior, risk for pregnancy, substance abuse and depression separately from their parents is important.
“Having a clinic set up where, traditionally, you do have time [to talk] separately with the adolescent, so that it doesn’t seem odd, and then respecting their privacy in how your portal is set up” is beneficial, she said. “All of these things are important discussions, and you can certainly have general conversations with the parents present regarding recommendations for future pregnancy planning.”
Clinics may differ in how they prescribe contraception. Some may provide referrals to a primary care or OB-GYN clinic.
According to the presentation, prescription of contraceptives within a lipid clinical may involve verbal education; a verbal or written contract such as a statin agreement; medical record documentation; or routine pregnancy testing similar to what is used by dermatologists for the prescription of isotretinoin.
“Why would we not wait until after childbearing age,” Liebeskind said during the presentation. “We now have some outcomes of statin therapy in children with 20-year follow-up data. Granted, it was a small number of 214 children with genetically confirmed familial hypercholesterolemia, but still an important study where these children started pravastatin during childhood. It did confer reduction in vascular events in association with early initiation of that LDL-lowering therapy, as well as slowed progression of carotid intima-media thickness.”
According to the presentation, participants with familial hypercholesterolemia were assessed though age 39 years, and researchers observed significantly greater freedom from death from CV causes compared with their parents with familial hypercholesterolemia.
Liebeskind added that lipid evaluation in adolescents of childbearing age may not only be done to determine the appropriateness of statin initiation, but to monitor the effect of contraceptives on lipid levels as well.
According to the presentation, the estrogenic component of hormonal therapies is generally considered to raise triglycerides, and guidelines encourage caution in contraceptive prescription if baseline triglycerides are 250 mg/dL to 500 mg/dL.
Moreover, the androgenic progesterone component of contraceptive drugs such as norgestrel and levonorgestrel is found to elevate LDL and decrease HDL.
“Lipid neutral contraceptives, for the most part, would be barrier methods and nonhormonal IUDs. With transdermal or vaginal oral contraceptives, it is important to realize they have similar risks to oral contraceptives,” Liebeskind said during the presentation. “Using a patch or vaginal hormones is not necessarily the better way out. It is also important to realize that the risk of thrombosis in pregnancy is greater than the risk of thrombosis as well on contraceptives. So, if you are concerned realizing that there is a quite low risk of thrombosis on contraceptives, the trade-off of getting pregnant is not necessarily a better one.”
References:
- Karalis DG, et al. J Clin Lipidol. 2016;doi:10.1016/j.jacl.2016.07.002.
- Kusters DM, et al. Expert Rev Cardiovasc Ther. 2012;doi:10.1586/erc.11.196.
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Liebeskind A. Session II: Ethical dilemmas in lipidology. Presented at: National Lipid Association Scientific Sessions; Dec. 10-12, 2020 (virtual meeting).
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