Less abnormal uterine bleeding with dabigatran than warfarin in women treated for acute venous thromboembolism

Huisman, Menno V.; Ferreira, Melanie; Feuring, Martin; Fraessdorf, Mandy; Klok, Frederikus A.

doi:10.1111/jth.14226

Cited by 43 publications

(33 citation statements)

References 20 publications

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“…The safety and efficacy of dabigatran in treatment of VTE disease has been well established, and there is ample experience with this specific agent in clinical practice. As opposed to evidence from the post hoc analyses of the factor Xa inhibitor licensing trials, a significantly lower risk of abnormal uterine bleeding in premenopausal women with VTE treated with dabigatran compared with warfarin (OR, 0.59; 95% CI, 0.39–0.90) was found in a recent post hoc analysis of the pooled RE‐COVER‐I, RE‐COVER‐II, and RE‐MEDY trials 13 . Anticoagulant‐associated HMB may be reduced while on thrombin inhibitor compared with VKA, but a thrombin inhibitor has not been compared directly to a factor Xa inhibitor in this context.…”

Section: Rationale For Including Patients With Any Indication For Facmentioning

confidence: 70%

“…trials. 13 Anticoagulant-associated HMB may be reduced while on thrombin inhibitor compared with VKA, but a thrombin inhibitor has not been compared directly to a factor Xa inhibitor in this context.…”

Section: Rationale For Including Patients With Any Indication For Fmentioning

confidence: 99%

“…In the AMPLIFY trial, the rate of abnormal uterine bleeding did not differ between apixaban and VKA (odds ratio [OR], 1.2; 95% CI, 0.7‐2.0), but clinically relevant nonmajor bleeding was more likely of vaginal origin in apixaban‐treated women 12 . Remarkably, a post hoc analysis of the VTE trials with dabigatran reported that treatment with dabigatran appears to be associated with a lower risk of abnormal uterine bleeding than VKA (OR, 0.6; 95% CI, 0.4–0.9) 13 …”

Section: Introductionmentioning

confidence: 99%

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Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study

Hamulyák

Wiegers

Scheres

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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Background In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA). Treatment with the direct oral thrombin inhibitor dabigatran appears to be associated with a reduced risk of HMB compared with VKA. These findings come from small observational studies or post hoc analyses of trials in which HMB was not a primary outcome. Use of tranexamic acid during the menstrual period may be effective in patients with HMB, but prospective data regarding efficacy and safety in patients on anticoagulant treatment are lacking. Rationale and Design A direct comparison of a factor Xa inhibitor and a thrombin inhibitor with HMB as primary outcome, as well as an evaluation of the effects of adding tranexamic acid in women with anticoagulant‐associated HMB is highly relevant for clinical practice. The MEDEA study is a randomized, open‐label, pragmatic clinical trial to evaluate management strategies in premenopausal women with HMB associated with factor Xa inhibitor therapy. Outcomes Women using factor Xa inhibitors with proven HMB, as assessed by a pictorial blood loss assessment chart (PBAC) score of >150, will be randomized to one of three study arms: (i) switch to dabigatran; (ii) continue factor Xa inhibitor with addition of tranexamic acid during the menstrual period; or (iii) continue factor Xa inhibitor without intervention. The primary outcome is the difference in PBAC score before and after randomization. Here, we present the rationale and highlight several unique features in the design of the study.

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Section: Rationale For Including Patients With Any Indication For Facmentioning

confidence: 70%

Section: Rationale For Including Patients With Any Indication For Fmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study

Hamulyák

Wiegers

Scheres

et al. 2021

Research and Practice in Thrombosis and Haemostasis

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“…An individual patient data meta‐analysis of the phase 3 trials showed that major bleeding of vaginal origin, although rare, occurred more often with use of factor Xa‐inhibitor than with VKA (17/10595 vs. 3/10957) . In contrast, data from the pooled RE‐COVER and RE‐MEDY trials (n = 1280), in which the effect of direct thrombin inhibitor dabigatran was evaluated, showed an overall AUB rate of 5.9% with dabigatran, compared to 9.6% with VKA (OR 0.6; 95% CI 0.4‐0.9) …”

Section: Periodmentioning

confidence: 95%

“…However, after this time, a temporary dose reduction of rivaroxaban or interruption of anticoagulation for the first days of the menstrual period was found to decrease menstrual bleeding without increasing risk of VTE . Switching treatment from a factor Xa inhibitor to dabigatran may be a reasonable option with regard to heavy menstrual bleeding but requires further investigation …”

Section: Periodmentioning

confidence: 99%

Sex matters: Practice 5P's when treating young women with venous thromboembolism

Bistervels

Scheres

Middeldorp

2019

Journal of Thrombosis and Haemostasis

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Sex matters when it comes to venous thromboembolism (VTE). We defined 5P'speriod, pill, prognosis, pregnancy, and postthrombotic syndrome -that should be discussed with young women with VTE. Menstrual blood loss (Period) can be aggravated by anticoagulant therapy. This seems particularly true for direct oral anticoagulants.Abnormal uterine bleeding can be managed by hormonal therapy, tranexamic acid, or modification of treatment. The use of combined oral contraceptives (Pill) is a risk factor for VTE. The magnitude of the risk depends on progestagen types and estrogen doses used. In women using therapeutic anticoagulation, concomitant hormonal therapy does not increase the risk of recurrent VTE. Levonorgestrel-releasing intrauterine devices and low-dose progestin-only pills do not increase the risk of VTE. In young women VTE is often provoked by transient hormonal risk factors that affects prognosis. Sex is incorporated as predictor in recurrent VTE risk assessment models.However, current guidelines do not propose using these to guide treatment duration.Pregnancy increases the risk of VTE by 4-fold to 5-fold. Thrombophilia and obstetric risk factors further increase the risk of pregnancy-related VTE. In women with a history of VTE, the risk of recurrence during pregnancy or post partum appears to be influenced by risk factors present during the first VTE. In most women with a history of VTE, antepartum and postpartum thromboprophylaxis with low-molecular-weight heparin is indicated. Women generally are affected by VTE at a younger age then men, and they have to deal with long-term complications (Post-thrombotic syndrome) of deep vein thrombosis early in life. K E Y W O R D Santicoagulants, contraceptives, female, pregnancy, venous thromboembolism

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Naringenin has an inhibitory effect on rivaroxaban in rats both in vitro and in vivo

Shi

Zhao

Chen

et al. 2021

Pharmacology Res & Perspec

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Food–drug interactions are reported to have some impacts on the pharmacokinetics and pharmacodynamics of various oral drugs. To better understand the effects of naringenin, one natural product in many fruits, on the pharmacokinetics of rivaroxaban, drug–drug interactions (DDIs) between naringenin and rivaroxaban in vitro were investigated in Sprague–Dawley (SD) rat liver microsomes. For the DDIs in vivo, 12 male SD rats were randomly divided into the experimental group and the control group with six rats in each group. Rats in the experimental group were pre‐treated with naringenin (10 mg/kg/day) for 2 weeks before the administration of rivaroxaban (10 mg/kg) by oral gavage, while the rats in the control group were given rivaroxaban (10 mg/kg) only once. The plasma concentration of rivaroxaban in rats was then measured by UPLC‐MS/MS. In vitro data indicated that naringenin could decrease the metabolic clearance rate of rivaroxaban with the IC 50 value of 38.89 μM, and exhibited a mixed inhibition to rivaroxaban (Ki =54.91 μM, aKi =73.33 μM, a = 0.74). In vivo data in rats revealed that as compared with that of the control group, the AUC (0– t ) value of rats in the experimental group was increased from 2406.28 ± 519.69 μg/h/L to 4005.04 ± 1172.76 μg/h/L, the C max value was increased from 310.23 ± 85.76 μg/L to 508.71 ± 152.48 μg/L, and the V z / F and CL z / F were decreased from 23.03 ± 4.81 L/kg to 16.2 ± 8.42 L/kg, 4.26 ± 0.91 L/h/kg to 2.57 ± 0.73 L/h/kg, respectively. These data indicated that naringenin had an inhibitory effect on the pharmacokinetics of rivaroxaban in rats, suggesting that the DDIs between naringenin and rivaroxaban might occur when they were co‐administered in the clinic.

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Less abnormal uterine bleeding with dabigatran than warfarin in women treated for acute venous thromboembolism

Cited by 43 publications

References 20 publications

Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study

Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study

Sex matters: Practice 5P's when treating young women with venous thromboembolism

Naringenin has an inhibitory effect on rivaroxaban in rats both in vitro and in vivo

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