When blood clots form in arms and legs, they tend to break off into pieces and block the lungs preventing breathing. Sometimes, quivering or irregular heartbeat can also lead to blood clots, stroke, heart failure, and other heart-related complications. People with such blood clots or prone to the formation of blood clots are often prescribed blood thinners called oral anticoagulants. Oral anticoagulants are drugs that prevent blood clotting and prolong the time taken to form a blood clot. Two types of oral anticoagulants are currently available – Vitamin K Antagonists (VKAs) that reduce blood clotting by decreasing the action of vitamin K and direct oral anticoagulants (DOACs) that directly inhibit the blood’s ability to form blood clots and do not require regular monitoring. Women on oral anticoagulants are at risk for prolonged menstrual bleeding or abnormal uterine bleeding, as well as other gynaecological bleedings. However, it is unknown whether DOACs are associated with a higher risk of abnormal uterine bleeding compared to VKAs. Severe bleeding episodes in women can impact a woman’s social, mental, physical, and emotional well-being, often leading to stopping of the blood thinners taken to prevent the formation of fatal blood clots. Our study's goal will be to assess whether the use of DOACs increases the risk of abnormal uterine bleeding compared with VKAs.
Anticoagulants are the treatment of choice in venous thromboembolism (VTE) and pulmonary embolism (PE). They are also prescribed in patients with nonvalvular atrial fibrillation (NVAF) in the prevention of stroke. Vitamin K-antagonists (VKAs), such as warfarin, have been the standard oral anticoagulant treatment for several decades. Direct oral anticoagulants (DOACs) are newer oral anticoagulants that specifically inhibit specific clotting factors. The efficacy, safety, and convenience of DOACs have led these agents to become the new standard of care. In particular, DOACs are associated with a lower risk of major bleeding such as intracranial haemorrhage compared with VKAs. However, the risk of gender-specific bleeding such as abnormal uterine bleeding associated with DOACs is unknown. Early experiences in using DOACs suggests an increase in heavy menstrual bleeding in women taking rivaroxaban, currently the main DOAC used for VTE treatment in the UK. Thus, we will conduct a population-based cohort study to assess whether the use of DOACs is associated with the incidence of abnormal uterine bleeding. We will form a cohort of all women aged between 15 and 50 years old newly prescribed DOACs or VKAs between 2008 and 2020. We will use Cox proportional hazards models to estimate hazard ratios with 95% confidence intervals of abnormal uterine bleeding associated with the use of DOACs compared with VKAs. In secondary analyses, we will assess whether this risk varies with duration of DOAC use and with indication for anticoagulation. Several sensitivity analyses will be performed to assess the robustness of our results.
Primary outcome: Abnormal uterine bleeding (Read codes and SNOMED-CT concept IDs outlined in Appendix 1)
Secondary outcome: anaemia
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Christel Renoux - Corresponding Applicant - McGill University
Haim Abenhaim - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Harika Dasari - Collaborator - Harvard University
Jonathan Michaud - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Sonia Hernandez-Diaz - Collaborator - Harvard University
HES Admitted Patient Care;ONS Death Registration Data