Direct oral anticoagulants for extended-duration thromboprophylaxis in hospitalized medically ill patients: are we there yet?

Despite a recommended 7-10 days of thromboprophylaxis, medically ill patients remain at increased risk of developing venous thromboembolism (VTE) after hospital discharge. Here, we present a contemporary review on the efficacy and safety of extended-duration thromboprophylaxis with direct oral anticoagulants (DOACs) in hospitalized medically ill patients. A search of publication and trial databases of controlled trials conducted from 2010 to 2016 using the key terms apixaban, rivaroxaban, and betrixaban showed three phase III trials that met our search criteria. In the "ADOPT" trial, apixaban was not inferior to enoxaparin in preventing VTE events (relative risk [RR] of 0.87; 95% confidence interval [CI] 0.62-1.23; P = 0.44); however, major bleeding rate was significantly higher with apixaban (RR of 2.58; 95% CI 1.02-7.24; P = 0.04). In the "MAGELLAN" trial, rivaroxaban was superior to enoxaparin in preventing VTE events (RR of 0.77; 95% CI 0.62-0.96; P = 0.02) but with higher clinically relevant bleeding rate (RR of 2.5; 95% CI 1.85-3.25; P < 0.001). Finally, in the "APEX" trial, there were no differences between betrixaban and enoxaparin in preventing VTE events in patients with elevated D-dimer levels (RR of 0.81; 95% CI 0.65-1.00; P = 0.054) and no differences in major bleeding events in all patients (RR of 1.19; 95% CI 0.67-2.12; P = 0.55). Compared with standard-duration thromboprophylaxis with enoxaparin, extended-duration thromboprophylaxis with DOACs in medically ill patients may provide an incremental benefit, although at the cost of increased bleeding events.