NATURE REVIEWS | CARDIOLOGY VOLUME 9 | JULY 2012 | 415 Zena and Michael A. Wiener Cardiovascular Institute, Mount Sinai School of Medicine, One Gustave L. Levy Place, PO Box 1030, New York, NY 10029‑6574, USA (J. M. Castellano, R. L. Narayan, P. Vaishnava, V. Fuster). Correspondence to: J. M. Castellano jmcastellano.cardio@ gmail.com Anticoagulation during pregnancy in patients with a prosthetic heart valve Jose M. Castellano, Rajeev L. Narayan, Prashant Vaishnava and Valentin Fuster Abstract | Effective anticoagulation is mandatory for pregnant women with mechanical heart valves. Oral anticoagulants offer the best maternal protection against thrombosis, but their use might be associated with an appreciable risk of fetal malformations and pregnancy loss. By contrast, heparin derivatives are associated with a reduced risk of fetal damage, but an increased risk of valve thrombosis in the mother, even with appropriate dose adjustment and monitoring of therapeutic efficacy. Given the varying risks of available anticoagulation strategies, and the paucity of data to inform the optimal approach, no single accepted treatment option exists for pregnant women with mechanical prosthetic valves. Although low‑molecular‑weight heparin is considered more efficacious than unfractionated heparin, treatment failures, even at therapeutic levels of factor Xa inhibition, have been reported. The risk of warfarin‑related embryopathy might be overstated, particularly at doses ≤5 mg daily. We advocate an individualized anticoagulation strategy that takes into account the patient’s preferences, calls for the use of vitamin K antagonists throughout pregnancy (substituted with a heparin derivative only close to term) for those patients at the greatest risk of thromboembolism, and relies on close multidisciplinary collaboration between the cardiac and obstetric care teams. Castellano, J. M. et al. Nat. Rev. Cardiol. 9, 415–424 (2012); published online 15 May 2012; doi:10.1038/nrcardio.2012.69 Introduction In the past 40 years, therapies for children and young adults with heart disease have improved dramatically. These improvements have led to a growing number of women of childbearing age with valvular heart disease as more patients survive to adulthood. 1 The first successful term pregnancy in a woman with a prosthetic heart valve was reported in 1966. 1 However, the therapeutic manage- ment of this population remains challenging; in particular, no clear consensus exists on the optimal prosthetic heart valve (when repair is not feasible) or the most suitable anti- coagulation strategy for patients who become pregnant. The association between mechanical valve prosthesis and adverse pregnancy outcomes has been recognized 2 and incorporated into a risk score for adverse cardiac compli- cations. 3 The presence of a mechanical heart valve confers a high risk of adverse outcomes and necessitates close monitoring by cardiac and obstetric care teams during pregnancy. 4 Oral anticoagulation therapy (with warfarin or other vitamin K antagonists) is the most effective strategy for preventing thromboembolic complications in pregnant women. 5 However, the use of oral anticoagulants during pregnancy is associated with increased fetal morbidity and mortality. The risk of embryopathy can be reduced by changing to unfractionated or low-molecular-weight heparin, either specifically during fetal organogenesis or for longer periods during pregnancy. 6 However, the risk of potentially life-threatening maternal thromboembolic complications is increased with heparin compared with oral anticoagulants. 7 No data on the efficacy of novel anti- coagulants (such as dabigatran and rivaroxaban) in patients with mechanical prosthetic heart valves are available, and the safety of these drugs in pregnancy has not been studied. Physicians should consider the hemodynamic, hemo- static, and metabolic alterations that are characteristic of pregnancy when choosing anticoagulant strategies for pregnant women with prosthetic heart valves. During pregnancy, the concentrations of several coagulation factors, including fibrinogen, increase, whereas stasis, vitamin-K-dependent activity, protein S activity, and fibrinolysis decrease, resulting in a hypercoagulable state and an increased risk of thromboembolism. 8 Drug pharmacokinetics can also be affected by pregnancy- related physiological changes, such as increases in glo- merular filtration rate (in the second semester) and plasma volume (which can affect volume of distribution of drugs). These physiological changes have implica- tions for the absorption, bioavailability, and clearance of anticoagulant medications. 9 Therapeutic decision-making for individual patients should be evidence-based, and physicians should consider the risks and benefits of the various anticoagulation treat- ments. In this Review, we discuss the controversies sur- rounding the choice of prosthetic heart valve in women of childbearing age and the advantages and disadvantages of various anticoagulation strategies during pregnancy. We suggest a framework for multidisciplinary decision- making that draws on the best available evidence and takes into account the need to consider the preferences of individual patients. Competing interests The authors declare no competing interests. FOCUS ON ANTICOAGULATION THERAPIES © 2012 Macmillan Publishers Limited. All rights reserved