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Thromb Haemost 2016; 116(04): 739-746
DOI: 10.1160/TH16-02-0087
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Treatment of venous thromboembolism with rivaroxaban in relation to body weight

A sub-analysis of the EINSTEIN DVT/PE studies
Marcello Di Nisio
1   Department of Medical, Oral and Biotechnological Sciences, University „G. D’Annunzio” of Chieti-Pescara, Chieti, Italy
,
Maria C. Vedovati
2   Internal and Cardiovascular Medicine and Stroke Unit, University of Perugia, Italy
,
Antoni Riera-Mestre
3   Department of Internal Medicine, Hospital Universitari de Bellvitge, IDIBELL, L’Hospitalet de Llobregat, and Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona, Spain
,
Martin H. Prins
4   University Medical Center, Maastricht, The Netherlands
,
Katharina Mueller
5   Bayer HealthCare AG, Germany
,
Alexander T. Cohen
6   Department of Haematological Medicine, Guys and St Thomas’ Hospitals, King’s College Hospital, London, UK
,
Philip S. Wells
7   Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ontario, Canada
,
Jan Beyer-Westendorf
8   University Hospital “Carl-Gustav Carus”, Department of Vascular Medicine, Technische Universität Dresden, Germany
,
Paolo Prandoni
9   Department of Cardiovascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy
,
Henri Bounameaux
10   Division of Angiology and Hemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland
,
Dagmar Kubitza
5   Bayer HealthCare AG, Germany
,
Jonas Schneider
5   Bayer HealthCare AG, Germany
,
Ron Pisters
11   Department of Cardiology, Maastricht University Medical Centre, Maastricht, The Netherlands
,
Jan Fedacko
12   First Department Of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Košice, Slovakia
,
Ricardo Fontes-Carvalho
13   Department of Physiology, Faculty of Medicine, University of Porto, Porto, Portugal
14   Cardiology Department, Gaia Hospital Center, Gaia, Portugal
,
Anthonie W. A. Lensing
5   Bayer HealthCare AG, Germany
› Author Affiliations
Further Information

Publication History

Received: 03 February 2016

Accepted after major revision: 07 June 2016

Publication Date:
02 December 2017 (online)

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Summary

The pharmacokinetics of oral rivaroxaban are highly predictable and only affected to a limited extent by bodyweight; therefore, dose adjustments for bodyweight are not required. However, this raises concerns among physicians for potential under- or overdosing. This substudy of the randomised EINSTEIN DVT and EINSTEIN PE trials, which compared rivaroxaban with enoxaparin/vitamin K antagonist (VKA) therapy, aimed to determine the incidence of major bleeding in patients with a low bodyweight and recurrent venous thromboembolism (VTE) in patients with a high bodyweight during rivaroxaban or enoxaparin/VKA therapy. More than 8,000 patients with objectively diagnosed deepvein thrombosis or pulmonary embolism were included. Adjusted hazard ratios for recurrent VTE and bleeding were calculated using the Cox proportional hazards model. Analyses were performed for both the first 21 days of treatment and the whole treatment period. For rivaroxaban recipients, there was no association between bodyweight or body mass index (BMI) and risk of recurrent VTE (ptrend=0.87 and 0.62, respectively), major bleeding (ptrend=0.24 and 0.36, respectively) or clinically relevant bleeding (ptrend=0.17 and 0.63, respectively). Major bleeding events were numerically lower in rivaroxaban patients across all bodyweight and BMI categories. Hazard ratios for rivaroxaban vs enoxaparin/VKA were similar in all bodyweight and BMI categories, both during the first 21 days and the whole treatment period. The fixed-dose rivaroxaban regimen is not associated with an increased risk of major bleeding or recurrent VTE in patients with either a low or high bodyweight. A high BMI was not associated with an increased risk of recurrent VTE during anticoagulation.

Note: This study was presented at the 25th Congress of the International Society on Thrombosis and Haemostasis; June, 2015, Toronto, Canada. Trial registration: EINSTEIN DVT (NCT00440193), EINSTEIN PE (NCT00439777).

Keywords

Body mass index - bodyweight - rivaroxaban - venous thromboembolism
 

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