CardioExchange Archive

CardioExchange’s John Ryan asks Samuel Z. Goldhaber for his perspective on the Hokusai-VTE randomized trial comparing edoxaban and warfarin in patients with symptomatic venous thromboembolism. For a summary of the findings, see CardioExchange’s news coverage of the trial.

John Ryan: Why should clinicians pay attention to this study?

Goldhaber: Hokusai-VTE is breathtaking in its magnitude and scope — the largest ever randomized trial of anticoagulation for symptomatic deep-vein thrombosis (DVT) and pulmonary embolism (PE). It enrolled 8240 patients, including 3319 with PE. About 1000 of the patients with PE underwent more-detailed chest CT classification to determine whether they had right ventricular dysfunction, defined as an RV-to-LV diameter ratio >0.9. One third of PE patients met this criterion. RV dysfunction was also determined according to elevation of the biomarker NT-proBNP, measured in about 90% of PE patients and elevated in 28%.

The trial permitted downward adjustment of the standard 60-mg once-daily dose of edoxaban to 30 mg once daily for patients with impaired renal function or low body weight. Edoxaban’s safety was superior to that of warfarin, with 19% fewer major or clinically relevant nonmajor bleeding events. Most eye-catching were the results in PE patients with RV dysfunction (according to elevated NT-ProBNP). In this prespecified subgroup, edoxaban nearly halved the rate of recurrent VTE (from 6.2% with warfarin to 3.3%), demonstrating superior efficacy to warfarin.

John Ryan: Where do this trial and edoxaban fit on the entire spectrum of available anticoagulants?

Goldhaber: Edoxaban (Hokusai-VTE) joins the ranks of dabigatran (RE-COVER), rivaroxaban (EINSTEIN-DVT and EINSTEIN-PE), and apixaban (AMPLIFY) as a novel oral anticoagulant whose efficacy is noninferior to warfarin for preventing recurrent VTE and, like apixaban, superior to warfarin for the safety endpoint of major and clinically relevant nonmajor bleeding. But edoxaban goes a step further in efficacy: It is the first anticoagulant to demonstrate superiority for efficacy in any prespecified subgroup. The fact that edoxaban nearly halved the rate of recurrent VTE in patients with PE and RV dysfunction raises the question of whether edoxaban could be used without adjunctive systemic or pharmacomechanical thrombolysis for patients at the “healthier end” of the wide clinical spectrum of submassive PE. Hokusai-VTE is also the only trial of one of the four novel anticoagulant VTE drugs to test dose reduction for patients with impaired kidney function or low body weight. Low-dose edoxaban performed as well as standard-dose edoxaban with respect to efficacy and safety.

JOIN THE DISCUSSION

In light of the findings from Hokusai-VTE, how do you perceive edoxaban in the panoply of novel anticoagulants?