Efficacy and safety of direct oral anticoagulants during pregnancy; a systematic literature review

Abstract

IntroductionDirect oral anticoagulants (DOACs) are increasingly used for anticoagulation or prevention of thromboembolic events in conditions that may co-occur with pregnancy. However, evidence regarding efficacy and safety during pregnancy is scarce. AimTo review the current literature concerning the efficacy, safety and outcome of DOACs during pregnancy in humans. MethodsWe systematically searched the MedLine public database for all studies describing the use of DOACs during pregnancy published up to July 4th 2017. Results236 cases of DOAC use during pregnancy were reported. Rivaroxaban was the most reported DOAC (n = 178). DOACs were mostly used for prophylaxis or treatment of venous thromboembolism (n = 91). DOACs were discontinued within the first 2 months of pregnancy in 84%, maximum reported duration of use was 26 weeks. Pregnancy outcome data were available for 140 pregnancies. Thirty-nine pregnancies were electively terminated. In the remaining 101 pregnancies total miscarriage rate was 31% (n = 31) and live birth rate was 68% (n = 69, 1 missing). Foetal and neonatal abnormalities were reported in 8 pregnancies, of which at least half were suspected to be related to rivaroxaban use during the 1st trimester of pregnancy. In only 18% of cases (n = 42), the presence or absence of thrombotic and bleeding complications was reported. ConclusionThe limited available evidence raises concern regarding embryo-foetal safety, with high incidence of miscarriages and a 4% rate of anomalies with the use of rivaroxaban. Not enough data are available to judge safety and efficacy of the use of DOACs during pregnancy.