Treatment of venous thromboembolism with rivaroxaban in relation to body weight

Marcello Di Nisio; Maria C. Vedovati; Antoni Riera-Mestre; Martin H. Prins; Katharina Mueller; Alexander T. Cohen; Philip S. Wells; Jan Beyer-Westendorf; Paolo Prandoni; Henri Bounameaux; Dagmar Kubitza; Jonas Schneider; Ron Pisters; Jan Fedacko; Ricardo Fontes-Carvalho; Anthonie W. A. Lensing

doi:10.1160/TH16-02-0087

Thrombosis and Haemostasis, Table of Contents

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

¹Department of Medical, Oral and Biotechnological Sciences, University „G. D’Annunzio” of Chieti-Pescara, Chieti, Italy

,

Maria C. Vedovati

²Internal and Cardiovascular Medicine and Stroke Unit, University of Perugia, Italy

,

Antoni Riera-Mestre

³Department 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

⁴University Medical Center, Maastricht, The Netherlands

,

Katharina Mueller

⁵Bayer HealthCare AG, Germany

,

Alexander T. Cohen

⁶Department of Haematological Medicine, Guys and St Thomas’ Hospitals, King’s College Hospital, London, UK

,

Philip S. Wells

⁷Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ontario, Canada

,

Jan Beyer-Westendorf

⁸University Hospital “Carl-Gustav Carus”, Department of Vascular Medicine, Technische Universität Dresden, Germany

,

Paolo Prandoni

⁹Department of Cardiovascular Sciences, Vascular Medicine Unit, University of Padua, Padua, Italy

,

Henri Bounameaux

¹⁰Division of Angiology and Hemostasis, University Hospitals of Geneva and Faculty of Medicine, Geneva, Switzerland

,

Dagmar Kubitza

⁵Bayer HealthCare AG, Germany

,

Jonas Schneider

⁵Bayer HealthCare AG, Germany

,

Ron Pisters

¹¹Department of Cardiology, Maastricht University Medical Centre, Maastricht, The Netherlands

,

Jan Fedacko

¹²First Department Of Internal Medicine, Pavol Jozef Safarik University and Louis Pasteur University Hospital, Košice, Slovakia

,

Ricardo Fontes-Carvalho

¹³Department of Physiology, Faculty of Medicine, University of Porto, Porto, Portugal

¹⁴Cardiology Department, Gaia Hospital Center, Gaia, Portugal

,

Anthonie W. A. Lensing

⁵Bayer HealthCare AG, Germany

› Author Affiliations

Abstract

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 (p_trend=0.87 and 0.62, respectively), major bleeding (p_trend=0.24 and 0.36, respectively) or clinically relevant bleeding (p_trend=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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References

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