Managing high cholesterol during pregnancy ‘challenging,’ medications lack safety data

Key takeaways:

• Many lipid-lowering medications do not have human safety data to recommend use during pregnancy and postpartum.
• Emerging data suggest statins are safe for some pregnant women, despite previous recommendations.

Most lipid-lowering medications lack safety data for pregnant and lactating women, complicating management of hyperlipidemia and hypertriglyceridemia, but data suggest statins can be used for those at high risk for cardiovascular events.

“Lipid metabolism does change during pregnancy and postpartum, and this is a natural process that happens during all normal pregnancies. There are several changes that occur to hormones, including an increase in estrogen as well as an increase in cholesterol and LDL synthesis. All of this is to produce fetal development, as lipids are an essential component of cells,” Emily Schwabe, PharmD, BSPC, clinical pharmacy specialist in medication safety at BJC Healthcare, said during a presentation at the American College of Cardiology Cardio-Obstetrics Essentials meeting. “This coincides with decreased liver lipase activity, and all of that does lead to some changes in serum lipid levels that [you should] expect when you see pregnant patients.”

During pregnancy, total cholesterol increases 25% to 50%, LDL cholesterol increases by 50% and triglyceride levels increase from 200% to 400%, according to Schwabe. In addition, between one in 250 to 300 women have familial hypercholesterolemia (FH) and statins are the main treatment option; however, time off statins during pregnancy and breastfeeding may be associated with increased morbidity and mortality rates, Schwabe said.

Managing cholesterol during pregnancy

Many medications for lowering lipids during pregnancy and lactation lack proper human safety data, Schwabe said. Currently, bile acid sequestrants are considered the safest option for pregnant women because they have a decreased absorption of fat-soluble vitamins with the potential to increase bleeding risks in newborns. They are also considered compatible during lactation, Schwabe said.

The National Lipid Association does not recommend niacin for lipid lowering during pregnancy; however, Schwabe said evidence suggests it is safe to take during pregnancy and lactation in recommended amounts.

The following lipid-lowering medications lack safety data for pregnant and postpartum women:

• ezetimibe;
• gemfibrozil;
• fenofibrate;
• PCSK9 inhibitors;
• bempedoic acid (Nexletol, Esperion Therapeutics);
• evinacumab-dgnb (Evkeeza, Regeneron); and
• lomitapide (Juxtapid, Chiesi).

In addition, Schwabe said, AbbVie recommends avoiding lactation for 5 days after final fenofibrate dose.

Statins for preeclampsia

Statins have been contraindicated in pregnancy since the first statin was FDA approved in 1987, Schwabe said. However, in July 2021, the FDA issued a communication to remove its strongest warning, noting that contraindicating statin therapy for all pregnant women is not appropriate.

Some evidence for statin safety during pregnancy stems from previous studies such as a 2015 Medicaid cohort study that demonstrated no significant teratogenic effects for pregnant women after first-trimester exposure to statins, a 2016 systematic review that found no clear relationship of congenital abnormalities with prenatal statin use and a 2017 retrospective cohort study that demonstrated an increased miscarriage rate with statin-exposed vs. non-exposed pregnant women, but researchers noted potential additional confounders not accounted for.

Researchers are investigating pravastatin use in pregnancy because it is a hydrophilic medication that will not cross the placenta as much as other medications, Schwabe said. In a randomized pilot clinical trial, researchers evaluated pravastatin vs. placebo in pregnant women at 12 to 17 weeks’ gestation at high risk for preeclampsia. Researchers observed no significant differences in maternal or neonatal adverse events, congenital anomalies or maternal and neonatal blood chemistries. Researchers also observed a potential benefit of lower preeclampsia and preterm delivery rates in the pravastatin group, but the study was not powered to detect such differences, Schwabe said.

In a multicenter, double-blind, placebo-controlled trial, researchers assessed more than 1,000 pregnant women at 35 and 37 weeks’ gestation at high risk for preeclampsia. Participants were randomly assigned to pravastatin 20 mg daily or placebo, and researchers observed no difference in preeclampsia risk reduction.

For the INOVASIA study, an open-label, randomized controlled trial, researchers evaluated pregnant women at 14 to 20 weeks’ gestation at high risk for preeclampsia randomly assigned to pravastatin 20 mg twice daily vs. aspirin 80 mg daily plus calcium 1 g daily. Results demonstrated lower preterm delivery rates (P = .048), higher birth weights (P = .006), lower Apgar score at 1 minute (P = .002) and lower NICU admission rates (P = .026) for the pravastatin vs. aspirin plus calcium groups, Schwabe said.

Recommendations for high-risk women

Currently, the FDA recommends discontinuing statin use for most pregnant women and the 2018 European Society of Cardiology (ESC) guidelines similarly recommend discontinuing statin use during pregnancy. Schwabe said pregnant women should continue statins if they are at high risk for atherosclerotic CVD, such as those with FH and those with a prior atherosclerotic CVD event.

The FDA and ESC recommend breastfeeding women do not use statins.

“The management of hyperlipidemia and hypertriglyceridemia during pregnancy is challenging, but many of our medications lack safety information at this time and, while previously contraindicated during pregnancy, recent data suggests that statins can be considered for pregnant patients who are at high risk of cardiovascular events, such as those with familial hypercholesterolemia and those with acute coronary syndrome,” Schwabe said.

References:

• Bateman BT, et al. BMJ. 2015;doi:10.1136/bmj.h1035.
• Costantine MM, et al. Am J Obstet Gynecol. 2021;doi:10.1016/j.ajog.2021.05.018.
• Döbert M, et al. Circulation. 2021;doi:10.1161/CIRCULATIONAHA.121.053963.
• Karalis DG, et al. J Clin Lipidol. 2016;doi:10.1016/j.jacl.2016.07.002.
• McGrogan A, et al. Pharmacoepidemiol Drug Saf. 2017;doi:10.1002/pds.4176.