Direct oral anticoagulants for treatment of thromboembolic disease: Have we reached a plateau?

Abstract

patients with single- and double-positive APLS, or APLS patients who have previously presented with VTE without arterial events, who could benefit from DOACs. 10 Finally, the risk of bleeding on anticoagulation cannot be completely obviated, with a risk of major bleeding of approximately 1% – 3% on DOACs overall. There remains a group of high-risk patients, especially in the elderly NVAF cohort, where DOACs are withheld due to bleeding con-cerns. Accordingly, research into factor XIa inhibitors has been a focus of interest for the past decade, since it is well established that congenital FXI deficiency is rarely associated with spontaneous bleeding but affords protection from ischaemic stroke and VTE. 11 A recent phase 2 clinical trial showed equivalent efficacy of an oral FXIa inhibitor to LMWH in the setting of VTE prevention post orthopaedic surgery, with a low risk of bleeding, and further studies are needed to determine whether FXIa inhibitors can dissociate thrombosis from haemostasis. 11 FXII inhibitors are also cur-rently under development, although their use is likely to be restricted to inhibiting contact activation in those being trea-ted with extracorporeal circuits rather than for VTE and NVAF. 12 Are we there yet? Almost, but not quite. Because until we have answered this question for every patient group — why use VKAs or LMWH when a DOAC will do — then there is work yet to do.