TY - JOUR
T1 - Heavy menstrual bleeding on direct factor Xa inhibitors: Rationale and design of the MEDEA study
AU - Hamulyák, Eva N.
AU - Wiegers, Hanke M. G.
AU - Scheres, Luuk J. J.
AU - Hutten, Barbara A.
AU - de Lange, Maria E.
AU - Timmermans, Anne
AU - Westerweel, Peter E.
AU - Nijziel, Marten R.
AU - Kruip, Marieke J. H. A.
AU - ten Wolde, Marije
AU - Ypma, Paula F.
AU - Klok, Frederikus A.
AU - Nieuwenhuizen, Laurens
AU - van Wissen, Sanne
AU - Hovens, Marcel M. C.
AU - Faber, Laura M.
AU - Kamphuisen, Pieter W.
AU - Büller, Harry R.
AU - Middeldorp, Saskia
N1 - Funding Information: ENH, HMW, BAH, MEL, AT, PEW, MRN, MW, PFY, LN, SW, LMF, MMH, PWK, HRB have no conflicts of interest to declare. LJS was a PhD candidate of the CREW project (2013T083) funded by the Netherlands Heart Foundation from 2014 to 2018 and has received funding for the printing of his doctoral thesis from the Dutch Heart Foundation, Dutch Federation of Coagulation Clinics, Stichting tot Steun Promovendi Vasculaire Geneeskunde, Bayer, Daiichi Sankyo, LEO Pharma, and Pfizer. SM reports grants and personal fees from Bayer, BMS Pfizer, Boehringer Ingelheim, Daiichi Sankyo and Portola, during the conduct of the study; grants and personal fees from GSK and Aspen; and personal fees from Sanofi, outside the submitted work. FAK reports research grants from Bayer, Bristol‐Myers Squibb, Boehringer Ingelheim, Daiichi‐Sankyo, MSD, Actelion, the Dutch Heart Foundation, and the Dutch Thrombosis Association. MJK reports fees from Bayer and grants from the Dutch Thrombosis Foundation, Innovation Fund, the Netherlands Organization for Health Research and Development (ZonMW), Bayer, Daiichi‐Sankyo, Boehringer Ingelheim, Pfizer, and Obi, all paid to her institution. Funding Information: The MEDEA study is sponsored by Amsterdam UMC – location AMC, Department of Vascular Medicine. An unrestricted investigator‐initiated research grant by Boehringer Ingelheim BV is gratefully acknowledged. Boehringer Ingelheim BV was not involved in the study design or in the preparation of the current manuscript. Publisher Copyright: © 2020 Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/1
Y1 - 2021/1
N2 - 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.
AB - 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.
KW - dabigatran
KW - factor Xa inhibitors
KW - menorrhagia
KW - prospective studies
KW - tranexamic acid
UR - http://www.scopus.com/inward/record.url?scp=85097738474&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/rth2.12471
DO - https://doi.org/10.1002/rth2.12471
M3 - Article
C2 - 33537547
SN - 2475-0379
VL - 5
SP - 223
EP - 230
JO - Research and practice in thrombosis and haemostasis
JF - Research and practice in thrombosis and haemostasis
IS - 1
ER -