Venous Thromboembolism
Ingrid M. Bistervels
MD PhD candidate
1) Amsterdam UMC location University of Amsterdam, Department of Vascular Medicine, Amsterdam, the Netherlands 2) Amsterdam Cardiovascular Sciences, Pulmonary Hypertension & Thrombosis, Amsterdam, the Netherlands
Amsterdam, Noord-Holland, Netherlands
Andrea Buchmuller
Researcher
Centre d’Investigation Clinique 1408, INSERM, Centre Hospitalier Universitaire, Saint Etienne, France
Saint-Etienne, Rhone-Alpes, France
.jpg "Hanke M. Wiegers, MD photo")
Hanke M. Wiegers, MD
PhD Researcher
Department of Obstetrics and Gynaecology, University Medical Centers Amsterdam, University of Amsterdam, Amsterdam, Netherlands
Amsterdam, Noord-Holland, Netherlands
Fionnuala Ní Áinle
Consultant Haematologist
Department for Haematology, Mater Misericordiae University Hospital, Dublin, Ireland
Dublin, Dublin, Ireland
Bernard Tardy
PU, PH
Université Jean Monnet Saint-Étienne, CHU Saint-Étienne, CIC1408 , Mines Saint-Etienne, INSERM, SAINBIOSE U1059, F-42023 SAINT-ÉTIENNE, FRANCE
Saint-Etienne, Rhone-Alpes, France
Jennifer Donnelly
MD
1) Department of Obstetrics and Gynaecology, Rotunda Hospital and Mater Misericordiae University Hospital, Dublin, Ireland 2) Royal College of Surgeons in Ireland, Dublin, Ireland 3) School of Medicine, University College Dublin (UCD), Dublin, Ireland
Dublin, Dublin, Ireland
Peter Verhamme, MD, PhD
MD, PhD
University Hospitals Leuven, Belgium
Leuven, Vlaams-Brabant, Belgium
Anne F. Jacobsen
MD, PhD
1) Department of Obstetrics and Gynaecology, Oslo University Hospital, Oslo, Norway 2) Faculty of Medicine, University of Oslo, Hospital, Oslo, Norway
Oslo, Oslo, Norway
Anette T. Hansen
MD, PhD
1) Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark 2) Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark
Aarhus, Midtjylland, Denmark
Marc A. Rodger
Professor
Department of Medicine, McGill University, McGill University Health Center, Montreal, Quebec, Canada
Montreal, Quebec, Canada
Maria T. DeSancho, Master in Clinical Science
Professor of Clinical Medicine
Division of Hematology and Medical Oncology, Department of Medicine, Weill Cornell Medicine/New York Presbyterian Hospital, New York, United States
New York, New York, United States
Roman G. Shmakov
MD, PhD
Institute of Obstetrics, National Medical Research Center for Obstetrics, Gynecology and Perinatology named after V.I. Kulakov, Ministry of Healthcare of the Russian Federation, Moscow, Russia
Moscow, Moskva, Russia
Nick van Es, MD PhD
MD
Department of Vascular Medicine, Amsterdam University Medical Center, Amsterdam, The Netherlands
Amsterdam, Noord-Holland, Netherlands
Martin H. Prins
MD PhD
Department of Epidemiology and Technology Assessment, University of Maastricht, Maastricht, the Netherlands
Maastricht, Limburg, Netherlands
Celine Chauleur
Professor
Department of Obstetrics and Gynecology, Université Jean Monnet Saint-Étienne, University Hospital, INSERM, SAINBIOSE U1059, F-42023 SAINT-ÉTIENNE, FRANCE
Saint-Etienne, Rhone-Alpes, France
Saskia Middeldorp, MD PhD
Professor
Department of Internal Medicine, Radboud university medical center, Nijmegen, The Netherlands
Nijmegen, Gelderland, Netherlands
Pregnancy-related venous thromboembolism (VTE) is a leading cause of maternal morbidity and mortality. Thromboprophylaxis is indicated in pregnant women with a history of VTE. The optimal dose of low-molecular-weight heparin (LMWH) for antepartum and postpartum thromboprophylaxis is uncertain, as no randomized trials have been performed in this population.
Aims:
To compare the efficacy and safety of intermediate versus low-dose LMWH in pregnant women with a history of VTE.
Methods:
In this international, open-label randomized trial, pregnant women with a history of VTE were randomized before 14 weeks of gestational age to weight-adjusted intermediate-dose or fixed low-dose LMWH until 6 weeks postpartum. The primary efficacy outcome was objectively confirmed VTE. The primary safety outcome was major bleeding. Outcomes were centrally adjudicated.
Results:
A total of 1,110 pregnant women were randomized and included in the intention-to-treat population. VTE occurred in 11 of 555 (2.0%) women assigned to weight-adjusted intermediate-dose LMWH and in 16 of 555 (2.9%) assigned to fixed low-dose LMWH (relative risk [RR], 0.69; 95% confidence interval [CI], 0.32-1.47; P=0.33). VTE occurred antepartum in five (0.9%) and five (0.9%) women, and postpartum in six (1.1%) and 11 women (2.0%) in the intermediate-dose and low-dose groups, respectively. On-treatment VTE in the per-protocol population (N=972) occurred in 1.0% and 2.4% (RR, 0.43; 95%CI, 0.15-1.20). On-treatment major bleeding in the safety population (N=1,045) occurred in 4.4% and in 3.8% receiving intermediate-dose or low-dose LMWH, respectively (RR, 1.16; 95%CI, 0.65-2.09).
Conclusion(s):
In pregnant women with a history of VTE, weight-adjusted intermediate-dose LMWH during the combined antepartum and postpartum periods was not associated with a lower risk of recurrence than fixed low-dose LMWH. The suggestion of greater efficacy of intermediate-dose low-molecular-weight heparin vs. low-dose low-molecular weight heparin during the postpartum period should be regarded as hypothesis generating and needs confirmation in a future randomized controlled trial (ClinicalTrials.gov number, NCT01828697).