Results of a substudy published in Research and Practice in Thrombosis and Haemostasis suggest there is no statistically significant difference in menstrual hemorrhage in patients with venous thromboembolism (VTE) who are treated with rivaroxaban at 10 mg or 20 mg, compared with aspirin. However, because the lower dose of rivaroxaban was associated with a numerically lower frequency of menstrual flow duration and intensity, these results likely support the use of low-dose rivaroxaban in menstruating women.
The direct oral anticoagulant rivaroxaban may cause heavy menstrual bleeding, but, prior to this analysis, it was unclear whether this effect was dose related, or whether rivaroxaban was associated with heavier menstrual bleeding than aspirin.
These findings highlight “the need for clinicians to consider the impact on menstrual changes when anticoagulants or antiplatelets are used,” said lead study author Kochawan Boonyawat, MD, of Mahidol University in Bangkok, Thailand, who encouraged physicians to be “aware of these potential complications and to ask women about them.”
The substudy examined data from the EINSTEIN-CHOICE trial, in which researchers compared once daily rivaroxaban 20 mg, rivaroxaban 10 mg, and aspirin 100 mg as extended therapy for VTE in patients who had completed anticoagulant therapy of six to 12 months for proximal deep vein thrombosis or pulmonary embolism.
Dr. Boonyawat and colleagues evaluated the menstrual flow durations and intensities of the 362 menstruating patients enrolled in the EINSTEIN-CHOICE trial at 30, 90, 180, and 360 days. Flow duration and intensity at these time points were compared with values recorded prior to initiation of anticoagulant therapy.
Out of 134 women who received 20 mg rivaroxaban, 12-18% reported increased menstrual flow duration. Menstrual flow duration increases were reported in 6-12% of the 120 women who received rivaroxaban 10 mg compared with 9-12% of the 108 women in the aspirin group. Reported increases in menstrual flow intensity were 19-24%, 14-21%, and 13-20% for the rivaroxaban 20 mg, rivaroxaban 10 mg, and aspirin groups, respectively.
The researchers found no significant difference between treatment with rivaroxaban 20 mg versus aspirin regarding increase in menstrual flow duration (odds ratio [OR] = 1.36; 95% CI 0.62-2.96; p=0.63), with rivaroxaban 10 mg versus aspirin (OR=0.77; 95% CI 0.33-1.81; p=0.76), or with rivaroxaban 10 mg versus 20 mg (OR=0.57; 95% CI 0.26-1.25; p=0.21).
Looking at the two dose levels of rivaroxaban, there also was no significant difference between the 10 mg (OR=1.07; 95% CI 0.49-2.34; p=0.98) or 20 mg (OR=1.41; 95% CI 0.67-2.99; p=0.52) groups regarding increased menstrual flow intensity. While the number of women experiencing increased menstrual flow intensity was lower in the 10 mg group, no statistically significant difference was found between the 10 mg and 20 mg arms (OR=0.76; 95% CI 0.37-1.57; p=0.64).
Approximately 5.2%, 10.0%, and 4.6% of women in the rivaroxaban 20 mg, rivaroxaban 10 mg, and aspirin groups, respectively, reported iron supplementation at baseline. A history of heavy menstrual bleeding was reported in 1.5% of women treated with rivaroxaban 20 mg and 2.5% of women treated with rivaroxaban 20 mg. None of the women in the aspirin group had a history of heavy menstrual bleeding.
Dr. Boonyawat said that further research is required to determine whether the changes in menstrual patterns affect the quality of life in women treated with rivaroxaban. “We suspect it does in many cases, based on our clinical experience,” she noted.
A limitation of this study was the inclusion of women with a history of heavy menstrual bleeding, who might have taken action to reduce bleeding duration and intensity prior to enrollment.
Study authors report relationships with Bayer and Janssen, which sponsored the study.
Boonyawat K, Lensing AWA, Prins MH, et al. Heavy menstrual bleeding in women on anticoagulant treatment for venous thromboembolism: comparison of high- and low-dose rivaroxaban with aspirin. Res Pract Thromb Haemost. 2021;5:308-313.