Direct oral anticoagulants for acute venous thromboembolism: closing the circle?

I n the past decades, the two-stage treatment of initial paren-teral heparin followed by vitamin K antagonists has been the standard therapy for patients with acute venous thrombo-embolism (VTE). With the advent of direct oral anticoagu-lants (DOACs), previously known as new oral anticoagulants, this era has come to an end. In this issue of Circulation, Schulman et al 1 report on the results of the RECOVER II study that investigated the efficacy and safety of dabigatran for the treatment of acute VTE. The study included patients with acute deep vein thrombosis (DVT) and pulmonary embolism who were treated for 6 months with 150 mg of dabigatran twice daily or warfarin targeted to an international normalized ratio between 2 and 3, after initial parenteral heparin, mostly low-molecular-weight heparin (LMWH). The study shows that parenteral heparin followed by dabigatran was as effective as heparin overlapped with and followed by warfarin. The primary endpoint of recurrent symptomatic VTE occurred in 2.3% of patients random-ized to dabigatran and in 2.2% of patients randomized to warfarin. Moreover, bleeding was less frequent in the dabiga-tran group. Thus, the RECOVER II study confirms the results of the RECOVER study with an identical design. 2 This study completes the phase III clinical development program of dabigatran in VTE, further encompassing 2 studies for the long-term secondary prevention of recurrent VTE, totaling 9372 patients in 4 phase III studies. The REMEDY study showed comparable efficacy and less bleeding of dabigatran compared with warfarin in patients with an indication for long-term anticoagulant therapy and is the only warfarin-controlled study evaluating a DOAC for the long-term secondary prevention of VTE. 3 In the RESONATE study, a placebo-controlled study, dabigatran was effective in preventing recurrent VTE in patients who completed 6 to 18 months of anticoagulation and who were at risk for recurrence but had no compelling indication for continued anticoagulant therapy. 3 The RECOVER II study not only concludes the clinical development program of dabigatran, it is also the last of a series of phase III trials in the acute treatment of VTE with the 4 newcomers (ie, dabigatran, rivaroxaban, apixaban, and edoxaban). Whereas the RECOVER study was the first reported study in VTE, RECOVER II closes the circle. The results of all 4 DOACs for the acute treatment of VTE are summarized in the Table. 4–8 These results deserve some clinically important comments. First, all DOACs were shown consistently to …