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

Introduction: Direct 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. Aim: To review the current literature concerning the efficacy, safety and outcome of DOACs during pregnancy in humans. Methods: We systematically searched the MedLine public database for all studies describing the use of DOACs during pregnancy published up to July 4th 2017. Results: 236 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. Conclusion: The 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.