TY - JOUR
T1 - Impact of gender on safety and efficacy of Rivaroxaban in adolescents & young adults with venous thromboembolism
AU - Krause, Manuela
AU - Henningsen, Anna
AU - Torge, Antje
AU - Juhl, David
AU - Junker, Ralf
AU - Kenet, Gili
AU - Kowalski, Dorothee
AU - Limperger, Verena
AU - Mesters, Rolf
AU - Anonymous,
AU - Rocke, Angela
AU - Shneyder, Maria
AU - Clausnizer, Hartmut
AU - Schiesewitz, Hanna
AU - Nowak-Göttl, Ulrike
N1 - Funding Information:
The study was supported by grants from the Förderverein “ Schlaganfall und Thrombosen im Kindesalter e.V. ” and Interdisziplinäres Zentrum für Klinische Forschung (IZKF: CRA01-09 ), University of Münster. None of the aforementioned funding agencies had a role in study design, conduct, interpretation, or reporting. The explorative study part, e.g. the HrQoL assessment, was sponsored by an unrestricted grant donated by Biotest Ag (Langen, Germany). We thank Sarina Levy from Tel-Hashomer, Israel, for assisting in editing the manuscript.
Publisher Copyright:
© 2016 Elsevier Ltd
Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2016/12/1
Y1 - 2016/12/1
N2 - Background The objective of the present study was to evaluate safety and efficacy of Rivaroxaban (RIVA) being administered as a routine medication for patients with venous thromboembolism (VTE) in a multicenter outpatient cohort. Methods 212 consecutively admitted outpatients (14–<55 years) with VTE treated with standard RIVA were recruited between January 2013 and December 2015. Monitoring of RIVA trough levels along with anti-factor-Xa-activities, factor (F) VIII, Ristocetin-cofactor and von Willebrand factor antigen were performed. Safety endpoints were defined as significant bleeding requiring any medical intervention such as: dose reduction, withdrawal of RIVA or death related to therapy. Efficacy endpoints were defined as any re-VTE or thrombus progression during treatment. Findings Patients were followed over a median period of 16 months. The bleeding incidence rate per 100 patient-years was 17.8% in fertile/premenopausal women and 4.0% in men with an annualized re-VTE rate of 0.48% (women only). The median daily RIVA dose of 0.25 mg/kg in females was significantly higher compared to males with 0.21 mg/kg (p < 0.0001), clearly correlated to FXa-activities. In bleeders compared to non-bleeders median RIVA dose per kg/body weight was significantly higher (0.26 mg vs. 0.22 mg; p = 0.008). Multivariate analysis adjusted for gender, body mass index, RIVA dose and FVIII revealed an increased hazard of 3.4% in women to develop RIVA-induced bleeding. Additionally, a gradual decrease of FVIII per IU/ml was significantly associated with clinical relevant bleeding. Interpretation Our data demonstrated a high incidence of mucosal type bleeding in women on standard RIVA. This has clinical implications suggesting a need for RIVA monitoring in selected individuals that are at an increased bleeding risk. Funding The study was supported by grants from the pediatric/adolescent stroke foundation “Schlaganfall und Thrombosen im Kindesalter e.V.” and Interdisziplinäres Zentrum für Klinische Forschung (IZKF: CRA01-09), University of Münster. The explorative study part, e.g. the HrQoL assessment, was sponsored by an unrestricted grant donated by Biotest Ag (Langen, Germany).
AB - Background The objective of the present study was to evaluate safety and efficacy of Rivaroxaban (RIVA) being administered as a routine medication for patients with venous thromboembolism (VTE) in a multicenter outpatient cohort. Methods 212 consecutively admitted outpatients (14–<55 years) with VTE treated with standard RIVA were recruited between January 2013 and December 2015. Monitoring of RIVA trough levels along with anti-factor-Xa-activities, factor (F) VIII, Ristocetin-cofactor and von Willebrand factor antigen were performed. Safety endpoints were defined as significant bleeding requiring any medical intervention such as: dose reduction, withdrawal of RIVA or death related to therapy. Efficacy endpoints were defined as any re-VTE or thrombus progression during treatment. Findings Patients were followed over a median period of 16 months. The bleeding incidence rate per 100 patient-years was 17.8% in fertile/premenopausal women and 4.0% in men with an annualized re-VTE rate of 0.48% (women only). The median daily RIVA dose of 0.25 mg/kg in females was significantly higher compared to males with 0.21 mg/kg (p < 0.0001), clearly correlated to FXa-activities. In bleeders compared to non-bleeders median RIVA dose per kg/body weight was significantly higher (0.26 mg vs. 0.22 mg; p = 0.008). Multivariate analysis adjusted for gender, body mass index, RIVA dose and FVIII revealed an increased hazard of 3.4% in women to develop RIVA-induced bleeding. Additionally, a gradual decrease of FVIII per IU/ml was significantly associated with clinical relevant bleeding. Interpretation Our data demonstrated a high incidence of mucosal type bleeding in women on standard RIVA. This has clinical implications suggesting a need for RIVA monitoring in selected individuals that are at an increased bleeding risk. Funding The study was supported by grants from the pediatric/adolescent stroke foundation “Schlaganfall und Thrombosen im Kindesalter e.V.” and Interdisziplinäres Zentrum für Klinische Forschung (IZKF: CRA01-09), University of Münster. The explorative study part, e.g. the HrQoL assessment, was sponsored by an unrestricted grant donated by Biotest Ag (Langen, Germany).
UR - http://www.scopus.com/inward/record.url?scp=84995581999&partnerID=8YFLogxK
U2 - 10.1016/j.thromres.2016.09.007
DO - 10.1016/j.thromres.2016.09.007
M3 - Journal articles
C2 - 27687905
AN - SCOPUS:84995581999
SN - 0049-3848
VL - 148
SP - 145
EP - 151
JO - Thrombosis Research
JF - Thrombosis Research
ER -
