title: Treatment of venous thromboembolism with rivaroxaban in relation to body weight. A sub-analysis of the EINSTEIN DVT/PE studies.
abstract: 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 deep-vein 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.
authors.affiliation: Marcello Di Nisio, Department of Medical, Oral and Biotechnological Sciences, University "G. D'Annunzio" of Chieti-Pescara, Chieti, Italy, E-mail: mdinisio@unich.it.
authors.forename: Marcello
authors.initials: M
authors.lastname: Di Nisio
authors.forename: Maria C
authors.initials: MC
authors.lastname: Vedovati
authors.forename: Antoni
authors.initials: A
authors.lastname: Riera-Mestre
authors.forename: Martin H
authors.initials: MH
authors.lastname: Prins
authors.forename: Katharina
authors.initials: K
authors.lastname: Mueller
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Cohen
authors.forename: Philip S
authors.initials: PS
authors.lastname: Wells
authors.forename: Jan
authors.initials: J
authors.lastname: Beyer-Westendorf
authors.forename: Paolo
authors.initials: P
authors.lastname: Prandoni
authors.forename: Henri
authors.initials: H
authors.lastname: Bounameaux
authors.forename: Dagmar
authors.initials: D
authors.lastname: Kubitza
authors.forename: Jonas
authors.initials: J
authors.lastname: Schneider
authors.forename: Ron
authors.initials: R
authors.lastname: Pisters
authors.forename: Jan
authors.initials: J
authors.lastname: Fedacko
authors.forename: Ricardo
authors.initials: R
authors.lastname: Fontes-Carvalho
authors.forename: Anthonie W A
authors.initials: AW
authors.lastname: Lensing
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000627:therapeutic use*; D001835:Body Weight; D017984:Enoxaparin / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D000069552:Rivaroxaban / Q000008:administration & dosage / Q000627:therapeutic use*; D054556:Venous Thromboembolism / Q000188:drug therapy*; D014812:Vitamin K / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D014812:Vitamin K; D000069552:Rivaroxaban
keywords: Body mass index; bodyweight; rivaroxaban; venous thromboembolism