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Anticoagulation for Pregnant Women With Mechanical Heart Valves
Study Questions:
What is the optimal method of anticoagulation during pregnancy for women with mechanical heart valves (MHVs)?
Methods:
This systematic review included studies that described at least one of three anticoagulation strategies: vitamin K antagonists (VKAs) throughout pregnancy, therapeutic heparin throughout, and/or sequential treatment with heparin during the first trimester and VKA during the second and third trimesters. Primary outcomes were maternal mortality, thromboembolic complications, livebirths, and anticoagulant-related fetal adverse events (including embryopathy and fetopathy).
Results:
The analysis included 46 studies with 2,468 pregnancies in 1,874 women. VKAs throughout pregnancy were associated with 0.9% maternal mortality, 2.7% thromboembolism, 2.0% fetal adverse events, and 64.5% livebirths. Low molecular weight heparin (LMWH) throughout pregnancy had 2.9% maternal mortality, 8.7% thromboembolism, 0% fetal adverse events, and 92% highest livebirths. Sequential treatment resulted in 2.0% maternal mortality, 5.8% thromboembolism, 1.4% fetal adverse events, and 79.9% livebirths. Unfractionated heparin (UFH) alone resulted in 3.4% maternal mortality and 11.2% thromboembolism. Warfarin ≤5 mg/day during the first trimester was associated with 2.3% fetal anomalies.
Conclusions:
VKAs are associated with the least maternal risk, but lowest livebirths, while LMWH is associated with the highest number of livebirths. Neither sequential treatment nor low-dose warfarin eliminates the risk of adverse fetal outcomes. UFH throughout pregnancy has the highest risk of maternal morbidity.
Perspective:
Anticoagulation during pregnancy must balance maternal and fetal risks, but there is no optimal strategy. While VKAs are safer for the mother, LMWH is safer for the fetus. Contrary to the 2014 American Heart Association/American College of Cardiology Valvular Disease Guideline, the use of UFH throughout pregnancy is not supported by this review. The guideline also recommends warfarin throughout pregnancy if the dose is ≤5 mg/day, but this still confers 2.3% risk to the fetus. Sequential treatment with heparin during the first trimester does not eliminate fetal risk. Given the heterogeneity of existing studies, unanswered questions remain regarding the optimal protocol for anti-Xa levels with LMWH, specific international normalized ratio goals with VKAs, and the use of concomitant aspirin treatment. Patients need to be informed about the risks involved with each strategy and actively involved in decision making.
Keywords: Anticoagulants, Aspirin, Cardiac Surgical Procedures, Fetal Death, Fetal Diseases, Fibrinolytic Agents, Heart, Artificial, Heart Valve Diseases, Heart Valve Prosthesis, Heparin, Heparin, Low-Molecular-Weight, Live Birth, Maternal Mortality, Pediatrics, Pregnancy, Pregnancy Trimester, First, Pregnancy Trimester, Second, Pregnancy Trimester, Third, Thromboembolism, Vitamin K, Warfarin
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