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

Abstract

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.

Safety and Effectiveness of Edoxaban in Japanese Venous Thromboembolism Patients ― Final Analysis of One-Year Follow-up Data From a Japanese Postmarketing Observational Study (ETNA-VTE-Japan) ―

“…The present under-dose rates, however, were lower than those in the RIETE registry, which enrolled patients with VTE receiving DOAC mainly such as rivaroxaban or apixaban. 18 This may have been due to the appropriate dose reduction criteria, which have been established only for edoxaban of the DOAC available for VTE treatment. Approximately half of the patients discontinued edoxaban in 1 year, and the main reason for discontinuation was "completion of treatment as planned".…”

Physician’s Adherence to Clinical Guidelines for in-Hospital Anticoagulant Prescribing

“…Пациентам с ТГВ для начальной терапии в 98% случаев назначались НМГ, хотя для половины случаев можно было назначить ПОАК. Для сравнения, в регистре «RIETE» описано 1635 случаев назначения ПОАК для начальной терапии ТГВ, которые не уступали гепаринам в безопасности и эффективности [27]. В аналогичном отечественном исследовании [28] ПОАК не рассматривались в качестве терапии ТГВ (в том числе начальной) из-за того, что данное показание появилось в инструкциях по медицинскому применению ПОАК совсем недавно.…”

Utility of a Nurse-Led Pathway for Patients with Acute Venous Thromboembolism Discharged on Rivaroxaban: A Prospective Cohort Study

“…However, this has been reported to be as high as 10 to 20% in other studies. 13,28,29 We demonstrated that these patients could be identified quickly through our nurse-led pathway and that timely corrective action and education were easily instituted by telephone.…”