Déjà vu all over again: a recurrent flaw in anticoagulant study design.

Abstract

The availability of direct oral anticoagulants (DOACs) rapidly changed the landscape of anticoagulation between 2010-present. Randomized controlled trials demonstrating efficacy with similar or superior safety compared to warfarin led to widespread use of DOACs in male and female patients of all ages. Years later, post-marketing data demonstrated a markedly increased rate of heavy menstrual bleeding (HMB) with rivaroxaban that had gone undetected in registry trials. Factor XI (FXI) inhibitors are currently being investigated as another alternative to available anticoagulation agents. While generally mild, the phenotype of inherited FXI deficiency includes bleeding in tissues with enhanced fibninolysis, including HMB. Thus, we aimed to perform a systematic review of published studies on FXI inhibitors in order to estimate rates of HMB. However, we found that few studies included menstruating individuals and even fewer specifically reported on uterine bleeding, highlighting once again a flaw in our approach to conducting trials of new anticoagulants.