Trujillo-Santos Javier, Di Micco Pierpaolo, Dentali Francesco, Douketis James, Díaz-Peromingo José Antonio, Núñez Manuel Jesús, Cañas Inmaculada, Mastroiacovo Daniela, Saraiva de Sousa Marta, Monreal Manuel
Prof. Manuel Monreal, MD, PhD, Department of Internal Medicine, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet s. n., 08916 Barcelona, Spain, E-mail:
Thromb Haemost. 2017 Jan 26;117(2):382-389. doi: 10.1160/TH16-07-0494. Epub 2016 Oct 27.
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.
在静脉血栓栓塞症（VTE）患者中，使用非推荐剂量或方案（每日一次与每日两次）的直接口服抗凝剂（DOACs）对治疗结果的影响尚未得到研究。我们使用RIETE（静脉血栓栓塞症信息登记处）登记系统，比较根据产品标签推荐接受DOACs治疗的VTE患者与接受非推荐剂量和/或方案的患者的治疗结果。主要结局是治疗过程中的VTE复发率、大出血和死亡率。截至2016年3月，1635例VTE患者接受DOACs进行初始治疗，1725例接受长期治疗。对于初始治疗，1591例接受利伐沙班治疗的患者中有287例（18%）、44例接受阿哌沙班治疗的患者中有22例（50%）未接受推荐治疗。对于长期治疗，1611例接受利伐沙班治疗的患者中有217例（14%）、81例接受阿哌沙班治疗的患者中有29例（36%）、33例接受达比加群治疗的患者中有15例（46%）未接受推荐治疗。在使用DOACs治疗过程中，8例患者出现VTE复发，14例发生大出血，13例死亡。与接受推荐剂量和方案的患者相比，接受非推荐剂量和/或方案DOACs治疗的患者VTE复发率更高（校正后HR：10.5；95%CI：1.28 - 85.9），大出血率（校正后HR：1.04；95%CI：0.36 - 3.03）或死亡率（校正后HR：1.41；95%CI：0.46 - 4.29）相似。在我们的队列中，有不可忽视比例的VTE患者接受了非推荐剂量和/或方案的DOACs。这种使用方式可能与更差的治疗结果相关。
