Management of Arrhythmias in Pregnancy

Antiarrhythmic and anticoagulant medications during pregnancy

Risks of antiarrhythmic medications to the mother and fetus should be considered. Medications may affect the fetus if they cross the placenta. Fetal arrhythmias can potentially be treated by medications that cross the placenta. Dosing may be complicated by the higher volume status, increase in renal and hepatic blood flow, lower plasma protein concentration, and hormonal changes that can affect drug levels and efficacy. Safety of drugs to the child during breast feeding should also be considered.

Table 13.1 summarizes U.S. Food and Drug Administration (FDA) pregnancy categories for common antiarrhythmic and anticoagulant medications. However, classification is not provided for drugs approved after June 30, 2015, when the FDA removed common antiarrhythmic and anticoagulant medications from the Physician Labeling Rule format, requiring information to assist in counseling for pregnancy, lactation, and females and males of reproductive potential.

Table 13.2 summarizes pregnancy categories for commonly used drugs in arrhythmia management. Few drugs are in category B, where there is no evidence of harm in humans and risk to the fetus is assessed to be rare, but these drugs include lidocaine, pindolol, and sotalol. The most common category is C, for which there is a lack of adequate studies. Older drugs, with which there is more experience, may be preferable to newer drugs, with which there is less experience. Drugs that should be avoided include those in category D, for which there is evidence of risk, and category X, which includes contraindicated drugs. These drugs to be avoided include phenytoin (fetal hydantoin syndrome and bleeding risk), amiodarone (fetal thyroid abnormality), dronedarone (teratogenicity), warfarin (see below), and atenolol (evidence of fetal risk). Risks and benefits of drug therapy before, during, and after pregnancy should be discussed in detail with patients.

Anticoagulant drugs have potential risks for bleeding in the mother, but because some may also be potentially less effective due to lower drug concentrations with higher plasma volume, if continued anticoagulation is required, it may be preferable to use a drug for which anticoagulant effects can be monitored. In addition, it is not known for all agents whether they cross the placenta, and there may be bleeding risks for the fetus.

Warfarin crosses the placenta and is contraindicated in the first trimester because of the risks of teratogenic congenital defect, spontaneous abortion, fetal hemorrhage, and death. It is contraindicated during pregnancy except in patients with high-risk mechanical heart valves (e.g., older mechanical mitral valves or history of thromboembolism). In such patients, low-molecular-weight heparin (LMWH) can be used for bridging during the first trimester, but anticoagulant effect should be monitored. In patients on chronic anticoagulation with warfarin who are planning to become pregnant, substitution with LMWH should ideally be done prior to conception. Although warfarin can be resumed after the first trimester, LMWH or heparin can be substituted near term. Ideally, warfarin does not appear to pass into breast milk and so can be used in lactating women. The non-vitamin K oral anticoagulants (NOACs) should probably be avoided.

Dabigatran and rivaroxaban probably cross the placenta, but it is not known if apixaban and edoxaban cross the placenta. Anticoagulant effects may not be easily monitored or readily reversed, especially in the fetus. Risks and benefits should be carefully weighed, including risks of thromboembolism in the mother, bleeding risks, and adverse effects in the mother and fetus.