Abnormal Uterine Bleeding in Women Receiving NOACs
This section discusses the incidence of abnormal uterine bleeding in women receiving NOACs
In this section:
- What do we need to know?
- Incidence of abnormal uterine bleeding in women receiving NOACs
What do we need to know?
Abnormal uterine bleeding is defined as perceived variations in the normal menstrual cycle interfering with quality of life. It consists of:
- Heavy menstrual bleeding
- Prolonged menstrual bleeding
- Intermenstrual bleeding
- Post-menopausal bleeding
Heavy menstrual bleeding is a commonly encountered side effect of treatment with anticoagulants (blood thinners) in premenopausal women. It is more often encountered in women receiving anticoagulants for the treatment of VTE (blood clots) than in those with AF receiving anticoagulants for stroke prevention, because women with AF are usually beyond reproductive age.
Incidence of abnormal uterine bleeding in women receiving NOACs
A meta-analysis of safety outcomes from phase III clinical trials of the Factor Xa inhibitors (apixaban, edoxaban and rivaroxaban) for the treatment of VTE showed that women treated with Factor Xa inhibitors experienced more clinically significant bleeding events (i.e. major bleeding or a bleeding event that prompts a patient to seek medical attention) than men.
Post hoc analyses from the EINSTEIN PE, EINSTEIN DVT and AMPLIFY trials suggest that this is due to an increased incidence of abnormal uterine bleeding.
Abnormal uterine bleeding in the EINSTEIN PE and EINSTEIN DVT trials
- EINSTEIN PE and EINSTEIN DVT were phase III clinical trials that compared rivaroxaban with standard therapy (enoxaparin overlapping with and followed by a VKA) for the acute treatment of PE and DVT, respectively
- Data from an analysis of 1737 women <60 years old who had not undergone hysterectomy enrolled in these trials showed that:
- Patient-reported abnormal uterine bleeding was twice as common in women treated with rivaroxaban, as opposed to enoxaparin/VKA
- Uterine bleeding that led to transfusion occurred more often in rivaroxaban- than enoxaparin/VKA-treated women
- Most women who experienced uterine bleeding necessitating transfusion were anaemic when anticoagulant treatment was initiated
Vaginal bleeding in the AMPLIFY trial
- AMPLIFY was a phase III trial that compared apixaban with standard therapy for the acute treatment of PE and DVT
- Data from a subgroup analysis of the 2228 women showed:
- The incidence of adjudicated non-major clinically relevant vaginal bleeding (i.e. vaginal bleeding that prompted a woman to seek medical attention) was similar between women treated with apixaban and those treated with enoxaparin/VKA (2.5% versus 2.1%)
- However, the proportion of non-major clinically relevant bleeding events classified as vaginal was more than threefold higher in women receiving apixaban than in those receiving enoxaparin/VKA (45% versus 20%)
- The majority of these events occurred in premenopausal women; premenopausal vaginal bleeding events on apixaban were more often characterized by prolonged bleeding than in those receiving enoxaparin/VKA
Real-world data on abnormal uterine bleeding in women receiving NOACs
The increased incidence of abnormal uterine bleeding in women receiving Factor Xa inhibitors observed in clinical trials is supported by real-world data, which suggests that heavy and/or prolonged menstrual bleeding is commonly reported by female patients receiving Factor Xa inhibitors for the treatment of VTE – it is important to note that most of the available data pertain to women receiving rivaroxaban
Data on bleeding events in women receiving Factor Xa inhibitors are also available from 178 German women of reproductive age who were enrolled in the prospective Dresden NOAC Registry or locally recruited into the phase III clinical trials of the NOACs:
- Mean treatment duration was over 1 year
- Fifty-seven (approximately one-third) of these women experienced 72 abnormal vaginal bleeding events, most of which were heavy menstrual bleeding
- Only six of these events were classified as major bleeding events
- Thirteen women experienced bleeding events unrelated to the menstrual cycle, which included endometrial hyperplasia, uterine myoma and isthmus polyps
- Most heavy menstrual bleeding events were managed conservatively, with 8 women requiring elective surgical intervention for treatment of underlying gynaecological abnormalities
- All of the women who experienced vaginal bleeding were able to continue with their anticoagulant therapy for the intended treatment duration
There is no evidence available to suggest an increase in abnormal uterine bleeding with dabigatran.
Approval No.: G.COM.GM.XA.10.2017.1875
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