Thromb Haemost 2017; 117(02): 382-389
DOI: 10.1160/TH16-07-0494
Stroke, Systemic or Venous Thromboembolism
Schattauer GmbH

Real-life treatment of venous thromboembolism with direct oral anticoagulants: The influence of recommended dosing and regimens

Javier Trujillo-Santos
1  Department of Internal Medicine, Hospital General Universitario Santa Lucía, Murcia, Spain
,
Pierpaolo Di Micco
2  Department of Internal Medicine and Emergency Room, Ospedale Buon Consiglio Fatebenefratelli, Naples, Italy
,
Francesco Dentali
3  Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy
,
James Douketis
4  Department of Medicine, St. Joseph’s Healthcare, McMaster University, Hamilton, Ontario, Canada
,
José Antonio Díaz-Peromingo
5  Department of Internal Medicine, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
,
Manuel Jesús Núñez
6  Department of Internal Medicine, Complejo Hospitalario de Pontevedra, Pontevedra, Spain
,
Inmaculada Cañas
7  Department of Internal Medicine, Hospital General de Granollers, Barcelona, Spain
,
Daniela Mastroiacovo
8  Department of Angiology, Ospedale SS. Filippo e Nicola, Avezzano, Italy
,
Marta Saraiva De Sousa
9  Department of Internal Medicine, Centro Hospitalar Gaia/Espinho, EPE. Vila Nova de Gaia, Portugal
,
Manuel Monreal
10  Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol de Badalona, Universidad Católica de Murcia, Murcia, Spain
,
RIETE Investigators› Author Affiliations
Financial support: Sanofi Spain supported this Registry with an unrestricted educational grant. Support by Bayer Pharma AG was limited to the part of RIETE outside Spain, which accounts for a 23.06 % of the total patients included in the RIETE Registry.
Further Information

Publication History

Received:04 July 2016

Accepted after major revision:06 October 2016

Publication Date:
01 December 2017 (online)

Summary

In patients with venous thromboembolism (VTE), the influence on outcome of using direct oral anticoagulants (DOACs) at non-recommended doses or regimens (once vs twice daily) has not been investigated yet. We used the RIETE (Registro Informatizado Enfermedad TromboEmbólica) registry to compare the outcomes in patients with VTE receiving DOACs according to the recommendations of the product label versus in those receiving non-recommended doses and/or regimens. The major outcomes were the rate of VTE recurrences, major bleeding and death during the course of therapy. As of March 2016, 1635 VTE patients had received DOACs for initial therapy and 1725 for long-term therapy. For initial therapy, 287 of 1591 patients (18 %) on rivaroxaban and 22 of 44 (50 %) on apixaban did not receive the recommended therapy. For long-term therapy, 217 of 1611 patients (14 %) on rivaroxaban, 29 of 81 (36 %) on apixaban and 15 of 33 (46 %) on dabigatran did not receive the recommended therapy. During the course of therapy with DOACs, eight patients developed VTE recurrences, 14 had major bleeding and 13 died. Patients receiving DOACs at non-recommended doses and/or regimens experienced a higher rate of VTE recurrences (adjusted HR: 10.5; 95 %CI: 1.28–85.9) and a similar rate of major bleeding (adjusted HR: 1.04; 95 %CI: 0.36–3.03) or death (adjusted HR: 1.41; 95 %CI: 0.46–4.29) than those receiving the recommended doses and regimens. In our cohort, a non-negligible proportion of VTE patients received non-recommended doses and/or regimens of DOACs. This use may be associated with worse outcomes.

* A full list of RIETE investigators is given in the Appendix.