The following are key points to remember from this review about the use of cardiovascular medications during pregnancy:

General

1. Several hemodynamic and physiologic adaptations occur during pregnancy and the pharmacokinetics of cardiovascular medications can change throughout gestation. Data on medication safety are often drawn from observational studies and expert opinion.
2. The Food and Drug Administration has replaced the ABCDX classification system for labeling the safety of medications during pregnancy with a narrative labeling system. The Pregnancy and Lactation Labeling Rule (PLLR) is intended to provide more information about available data, clinical considerations, and differences in degrees of fetal risk.

Arrhythmias

3. Unstable arrhythmias should be treated with electrical cardioversion. Antiarrhythmic medications should be avoided in the first trimester if possible, and the lowest effective dose should be used. Amiodarone should be avoided due to the risk of fetal thyroid and neurodevelopmental complications.
4. Supraventricular tachycardia (SVT) can be treated initially with vagal maneuvers, then adenosine, beta-blockers, and verapamil as third-line therapy. Beta-blockers (with or without digoxin) or oral verapamil can be used for suppressive therapy for SVT in the absence of pre-excitation. Sotalol or flecainide can be considered in the absence of structural heart abnormalities. In Wolff-Parkinson-White (WPW) syndrome, flecainide or propafenone are recommended for the prevention of SVT.
5. Atrial fibrillation and atrial flutter can be treated with beta-blockers, verapamil, and digoxin. Sotalol, flecainide, and propafenone can be considered if rhythm-control is needed. Intravenous procainamide is used for the treatment of atrial fibrillation with pre-excitation (wide complex tachycardia).
6. Beta-blockers are used frequently for the treatment of several cardiovascular conditions during pregnancy. Large, retrospective studies show no association between the use of beta-blockers and major congenital abnormalities. Beta-blockers are associated with intrauterine growth restriction (small for gestational age infants), increased risk of preterm birth, and neonatal bradycardia and hypoglycemia. Atenolol is not recommended due to increased risk of fetal growth restriction.
7. Digoxin can be used during pregnancy. Of note, the assay for measuring digoxin levels during pregnancy can result in falsely elevated levels due to circulating digoxin-like fragments.
8. Antiarrhythmics: Flecainide can be used during pregnancy. Adverse effects include maternal visual disturbance, prolongation of maternal QT interval, prolonged neonatal QT intervals and heart failure at toxic levels, cholestasis of pregnancy, and decreased fetal heart rate variability. Limited data exist about the use of propafenone during pregnancy. Sotalol portends increased risk of torsades de pointes due to QT prolongation and is typically only used for fetal arrhythmias.
9. Ventricular tachycardia (VT): Electric cardioversion should be performed for unstable VT. If a pregnant woman is hemodynamically stable, electric cardioversion or lidocaine or beta-blockers can be considered. European Society of Cardiology guidelines suggest procainamide, flecainide, or sotalol. Amiodarone should only be used if other treatments are ineffective.

Hypertension

10. The placenta does not autoregulate blood flow; therefore, acute maternal hypotension due to antihypertensive treatment may cause fetal distress.
11. First-line agents for chronic or gestational hypertension include labetalol, nifedipine, and methyldopa. Dose reduction may be needed in the second trimester when a 5-10 mm Hg decrease in mean blood pressure is often observed due to the physiologic changes of pregnancy. Diuretics can cause placental hypoperfusion.

Heart Failure

12. Beta-blockers can be used, and digoxin can be considered. Diuretics (furosemide, bumetanide, hydrochlorothiazide) can be used for pulmonary edema, but excessive dosing carries the risk of placental hypoperfusion and fetal electrolyte abnormalities.
13. During pregnancy, hydralazine plus nitrates can be used for afterload reduction (angiotensin-converting enzyme [ACE] inhibitors are contraindicated).
14. ACE inhibitors, angiotensin-receptor blockers, direct renin-inhibitors, angiotensin receptor-neprysilin inhibitors, spironolactone, and eplerenone are contraindicated.
15. Enalapril, captopril, and benazepril can be safely considered during lactation.

Statins

16. Statins continue to be considered contraindicated during pregnancy, although no associations with birth defects were found in a multicenter, observational, prospective trial and a recent systematic review. Gemfibrozil, fenofibrate, and ezetimibe are also considered potentially teratogenic.

Anticoagulation for Mechanical Valves

17. Embryopathy, miscarriage, and stillbirth are more common with daily doses of warfarin >5 mg. If the warfarin dose is >5 mg/day, women should switch to low molecular weight heparin (LMWH) or unfractionated heparin (UFH) by the end of the sixth week of gestation to decrease the risk of warfarin embryopathy.
18. LMWH does not cross the placenta. Meticulous monitoring of peak and trough anti-Xa levels need to be followed. Transition between warfarin and LMWH are times of increased risk for valve thrombosis and thromboembolic risk.
19. Women who are receiving warfarin should be changed to LMWH or UFH at 36 weeks' gestation to reduce the risk of fetal hemorrhage and maternal bleeding at the time of delivery.
20. Regional anesthesia cannot be given within 24 hours of the last dose of LMWH. Cesarean delivery should be performed if a mother arrives in labor while on warfarin. Reversal of warfarin with vitamin K in the mother does not ensure reversal in the fetus.

Antiplatelet Medications

21. Low-dose aspirin is considered safe during pregnancy and lactation, and is commonly used for the prevention of pre-eclampsia. High-dose aspirin should be avoided due to the risk of premature closure of the ductus arteriosus.
22. Clopidogrel has been used in pregnancy but since there are limited data, it is recommended to use it for the shortest duration possible. It must be discontinued 7 days prior to neuroaxial anesthesia to decrease the risk of epidural hematoma.

Pulmonary Arterial Hypertension

23. Parenteral and inhaled prostaglandins can be used in the appropriate setting and phosphodiesterase-5 inhibitors may be considered. Endothelin receptor blockers (bosentan, ambrisentan, macitentan) are teratogenic and should not be used.

Emergency Situations

24. Standard medications should be used for the treatment of cardiopulmonary resuscitation or cardiogenic shock.

Clinical Topics: Anticoagulation Management, Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Dyslipidemia, Heart Failure and Cardiomyopathies, Prevention, Anticoagulation Management and Atrial Fibrillation, Implantable Devices, EP Basic Science, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Congenital Heart Disease, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, Lipid Metabolism, Acute Heart Failure, Hypertension

Keywords: Adrenergic beta-Agonists, Angiotensin-Converting Enzyme Inhibitors, Anti-Arrhythmia Agents, Anticoagulants, Arrhythmias, Cardiac, Aspirin, Atrial Fibrillation, Gestational Age, Heart Failure, Heparin, Low-Molecular-Weight, Hypertension, Hypotension, Pharmacokinetics, Platelet Aggregation Inhibitors, Pre-Eclampsia, Pregnancy, Primary Prevention, Prostaglandins, Warfarin, Women, Wolff-Parkinson-White Syndrome

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