About Index

Hokusai-VTE

"Edoxaban versus Dalteparin for Cancer-Associated Venous Thromboembolism". The New England Journal of Medicine. 2017.

Links to original sources: Wiki Journal Post Full Journal Article

Clinical Question


Is oral edoxaban noninferior to subcutaneous dalteparin in preventing recurrent venous thromboembolism or major bleeding in patients with cancer?

Bottom Line


Edoxaban is noninferior to dalteparin with respect to the composite outcome of recurrent venous thromboembolism or major bleeding in patients with cancer.

Major Points


Venous thromboembolism is a frequent complication in patients with cancer which complicates their treatment and care. Low-molecular-weight heparin is the standard treatment; however, direct oral anticoagulants offer a potential for ease of use but their efficacy and safety in this scenario were unclear. In the Hokusai VTE Cancer trial, edoxaban compared to dalteparin was noninferior for the composite outcome of recurrent venous thromboembolism or major bleeding, though showing a higher rate of major bleeding particularly in patients with gastrointestinal cancer.

Guidelines


Current guidelines recommend low-molecular-weight heparin for the treatment of cancer-associated venous thromboembolism.

Design


Open-label, noninferiority, randomized controlled trial.

Population


1,046 adult patients with active cancer and acute symptomatic or incidentally detected venous thromboembolism.

Interventions


Patients were randomly assigned to receive oral edoxaban (60 mg once daily) or subcutaneous dalteparin (200 IU/kg once daily for one month, followed by 150 IU/kg once daily).

Outcomes


The primary outcome was a composite of recurrent venous thromboembolism or major bleeding within a 12-month period after randomization. Recurrent venous thromboembolism was lower in the edoxaban group (7.9% vs. 11.3%), but the rates of major bleeding were higher (6.9% vs. 4.0%) compared to the dalteparin group.

Criticisms


- Open-label design might introduce bias in reporting of outcomes. - The number of primary-outcome events was lower than expected, possibly affecting the power of the trial. - Median duration of the assigned treatment was shorter with dalteparin potentially influencing relative efficacy. - The trial had a broad spectrum of cancer patients with a wide array of therapies, thus limiting definitive conclusions about individual tumor types.

Funding


Daiichi Sankyo.

Further Reading


- New England Journal of Medicine, December 12, 2017, at NEJM.org. - Supplementary appendix material available for additional details on methods and outcomes.