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CC BY 4.0 · TH Open 2020; 04(03): e245-e254
DOI: 10.1055/s-0040-1716496
Review Article

Impact of Patient Characteristics on Treatment Outcomes in Symptomatic Venous Thromboembolism: Results of HOKUSAI-VTE Randomized Trial Analysis

Ben van Hout
1   Health Economics and Decision Science Division, University of Sheffield, Sheffield, United Kingdom
,
Emma Hawe
2   Data Analytics and Design Strategy Division, RTI-Health Solutions, Manchester, United Kingdom
,
Alexander T. Cohen
3   Department of Haematology, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom
› Author Affiliations Funding B.v.H., A.C., and E.H. received consulting support from Daiichi Sankyo in the development of this manuscript.
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Abstract

Introduction In patients with venous thromboembolism (VTE), direct oral anticoagulants (DOACs) such as edoxaban, apixaban, dabigatran, and rivaroxaban are more convenient, safer, and just as effective as vitamin K antagonists (VKAs). Limited information is known about the effects of patient characteristics on VTE efficacy and safety of DOACs compared with VKAs, without appropriate effect modifier adjustment comparisons of DOACs may be biased. This study considers the effect of variables that can modify the efficacy and safety of edoxaban and warfarin, using patient-level data.

Materials and Methods The primary efficacy and safety outcomes in the HOKUSAI-VTE study were VTE recurrence and clinically relevant bleeding, respectively. Potential effect modifiers were age, creatinine clearance, and weight. The relationship between the percentage of time in international normalized ratio (INR) control and outcomes were considered for the warfarin arm. Univariate and multivariate regression were performed for each patient characteristic.

Results The relationship between treatment and VTE recurrence differed by age (interaction p = 0.007) and by creatinine clearance (p = 0.05). VTE recurrence differed by age for patients in the warfarin arm but not for those in the edoxaban arm and differed by INR control in the warfarin arm (p < 0.005). A stronger relationship between creatinine clearance and clinically relevant bleeding was found in the warfarin arm than in the edoxaban arm (p = 0.04). Clinically relevant bleeding differed by the percentage of time in INR control in the warfarin arm (p < 0.005). Age appeared to be a more important effect modifier than creatinine clearance in patients with VTE.

Discussion The finding that efficacy in older patients was greater for those taking edoxaban than for those taking warfarin in the HOKUSAI-VTE study needs further investigation. Modification of the treatment effect by age for those taking warfarin might bias estimates of comparative effectiveness among DOACs if VKAs are the reference treatment.

Keywords

venous thrombosis - edoxaban - warfarin - creatinine - effect modification - age

Authors' Contributions

B.v.H. substantially contributed to concept and design, analysis, and/or interpretation of data; critical writing and revising the intellectual content; and has given final approval of the version to be published. A.T.C. provided a substantial contribution to concept and design, analysis, and/or interpretation of data; provided critical writing and revising of the intellectual content; and has given final approval of the version to be published. E.H. provided a substantial contribution to concept and design, analysis, and/or interpretation of data; provided critical writing and revising of the intellectual content; and has given final approval of the version to be published.


Supplementary Material



Publication History

Received: 17 July 2020

Accepted: 31 July 2020

Article published online:
23 September 2020

© .

Georg Thieme Verlag KG
Stuttgart · New York

 

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