What is the best cholesterol-reducing drug for a pregnant woman with hypercholesterolemia (high cholesterol)?

Best Cholesterol-Reducing Drug in Pregnancy

Bile acid sequestrants (cholestyramine, colestipol, or colesevelam) are the only cholesterol-lowering medications considered safe during pregnancy and are the best choice for pregnant women requiring lipid-lowering therapy. 1, 2

Primary Treatment Approach

First-Line Management

• Intensive lifestyle modifications—including a heart-healthy diet and increased physical activity—form the foundation of cholesterol management in pregnancy and should be implemented for all pregnant women with elevated lipids. 2
• Dietary and lifestyle measures should be optimized before, during, and after pregnancy. 2

Pharmacological Treatment When Necessary

Bile Acid Sequestrants: The Only Safe Option

• Bile acid sequestrants are not systemically absorbed, making them safe for use during pregnancy. 1
• The European Atherosclerosis Society recommends initiating bile acid sequestrants 3 months before planned pregnancy and continuing throughout pregnancy and lactation. 2
• Monitor patients on bile acid sequestrants for vitamin K deficiency during pregnancy. 1, 3

Medications to Avoid

Statins

• All statins should be discontinued at least 1 month and preferably 3 months before attempted conception, or immediately if pregnancy is discovered. 1, 3
• Women of childbearing age taking statins must use reliable contraception. 1, 3
• The FDA pravastatin label states to "discontinue pravastatin when pregnancy is recognized," though it notes that available data have not identified a drug-associated risk of major congenital malformations. 4

Other Lipid-Lowering Agents

• Avoid ezetimibe, PCSK9 inhibitors, bempedoic acid, fibrates, and niacin during pregnancy due to insufficient safety data or potential fetal risk. 2
• Ezetimibe should only be used if potential benefit justifies the risk to the fetus. 1
• Bempedoic acid should be discontinued when pregnancy is recognized unless benefits outweigh potential risks. 1

Special High-Risk Populations

Exception to Statin Discontinuation

For women with homozygous familial hypercholesterolemia (HoFH) or established atherosclerotic cardiovascular disease (ASCVD) at very high risk for heart attack or stroke, continuing statins during pregnancy may be considered after individual risk-benefit assessment. 1, 3

• The FDA has removed the absolute contraindication against statin use in pregnancy, allowing for individual risk-benefit assessment in these exceptional cases. 1
• Recent evidence from the American Diabetes Association suggests that statins did not increase teratogenic effects in individuals with familial hypercholesterolemia. 5
• A meta-analysis of pravastatin in pregnant individuals showed a reduction in preeclampsia, premature birth, and neonatal intensive care unit admissions. 5

Lipoprotein Apheresis

• Women with HoFH should continue or initiate lipoprotein apheresis during pregnancy, especially those with established ASCVD. 2
• If LDL-C goals are not achieved and apheresis is unavailable, continued statin use may be considered in HoFH patients with clinical ASCVD after the first trimester. 2

Monitoring During Pregnancy

• Monitor all pregnant women for significant elevations in LDL-C and triglycerides, recognizing that progressive rises are physiologic. 1, 2
• A 2-fold increase in triglycerides during the third trimester and 30-50% increases in total and LDL cholesterol are normal. 1
• Severe hypertriglyceridemia (≥500 mg/dL) poses risk of acute pancreatitis and may warrant intervention with dietary fat restriction. 1
• Referral to a lipid specialist is strongly recommended for pregnant women with severe hyperlipidemia. 1

Postpartum Management

• Lipid-lowering therapy may be resumed after completion of breastfeeding. 1, 2, 3
• Bile acid sequestrants remain the only safe pharmacological option during breastfeeding if treatment is necessary. 2

Common Pitfalls to Avoid

• Failing to discontinue statins before planned pregnancy in women taking them for primary prevention—the cardiovascular benefit during 9 months of pregnancy is negligible compared to potential fetal risks. 3
• Not providing adequate contraception counseling to women of childbearing age on statin therapy. 1, 3
• Overlooking the need to monitor for vitamin deficiencies when using bile acid sequestrants during pregnancy. 1