Comparison Between Non–vitamin K Antagonist Oral Anticoagulants and Low-Molecular-Weight Heparin in Asian Individuals With Cancer-Associated Venous Thromboembolism

Dong-Yi Chen,See-Tong Pang,Ming-Shien Wen,Ming-Jer Hsieh,Pao-Hsien Chu,Cheng-Keng Chuang,Chi-Nan Tseng,John Wen-Cheng Chang,Tien-Hsing Chen,Shang-Hung Chang,Jen-Shi Chen,Wen-Ching Lan,Shao-Wei Chen,Wen-Kuan Huang,I-Chang Hsieh,Lai-Chu See

doi:10.1001/jamanetworkopen.2020.36304

Abstract

It is unclear whether the clinical benefits associated with non-vitamin K antagonist oral anticoagulants (NOACs) are similar to those associated with low-molecular-weight heparins (LMWHs) in Asian individuals with cancer and acute venous thromboembolism (VTE). To compare the risk of recurrent thromboembolic events and bleeding associated with use of a NOAC vs use of the LMWH enoxaparin in Asian individuals with cancer-associated VTE. This cohort study was conducted using data from the Chang Gung Research Database, a multi-institutional electronic medical records database in Taiwan. A cohort of 1109 patients with cancer-associated VTE were identified between January 1, 2012, and January 31, 2019. Data were analyzed from March 2019 through December 2020. Receiving a NOAC (including rivaroxaban, apixaban, edoxaban, or dabigatran) or the LMWH enoxaparin. The primary outcomes were composite recurrent VTE or major bleeding. Stabilized inverse probability of treatment weighting was used to balance baseline covariates. We compared risks of recurrent VTE or major bleeding between groups using Cox proportional hazards models. In addition, we conducted an analysis using a Fine and Gray subdistribution hazard model that considered death as a competing risk. Among 1109 patients with cancer and newly diagnosed VTE, 578 (52.1%) were women and the mean (SD) age at index date was 66.0 (13.0) years; 529 patients (47.7%) received NOACs and 580 patients (52.3%) received the LMWH enoxaparin. Composite recurrent VTE or major bleeding occurred in 75 patients (14.1%) in the NOAC group and 101 patients (17.4%) in the enoxaparin group (weighted hazard ratio [HR], 0.77; 95% CI, 0.56-1.07; P = .11). The groups had similar risk of VTE recurrence (HR, 0.62; 95% CI, 0.39-1.01; P = .05) and major bleeding (HR, 0.80; 95% CI, 0.52-1.24; P = .32) at 12 months of follow-up. However, taking a NOAC was associated with a significantly lower risk of gastrointestinal bleeding compared with receiving enoxaparin (10 patients [1.9%] vs 41 patients [7.1%]; HR, 0.29; 95% CI, 0.15-0.59; P < .001). Findings for both primary outcomes were consistent with competing risk analyses (recurrent VTE: HR, 0.68; 95% CI, 0.45-1.01; P = .05; major bleeding: HR, 0.77; 95% CI, 0.51-1.16; P = .21). This cohort study found that in real-world practice, among Asian patients with cancer-associated VTE, use of a NOAC was associated with a similar risk for recurrent VTE or major bleeding compared with use of the LMWH enoxaparin. Nonetheless, use of a NOAC was associated with a significantly lower rate of gastrointestinal bleeding. Further prospective studies are needed to confirm these findings.

Highlights

Venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep vein thrombosis (DVT), is a common cause of morbidity and the second leading cause of mortality in individuals with cancers after disease progression.[1]
Composite recurrent venous thromboembolism (VTE) or major bleeding occurred in 75 patients (14.1%) in the non–vitamin K antagonist oral anticoagulant (NOAC) group and 101 patients (17.4%) in the enoxaparin group
This cohort study found that in real-world practice, among Asian patients with cancer-associated VTE, use of a NOAC was associated with a similar risk for recurrent VTE or major bleeding compared with use of the low-molecular-weight heparin (LMWH) enoxaparin

Summary

Introduction

Venous thromboembolism (VTE), comprising pulmonary embolism (PE) and deep vein thrombosis (DVT), is a common cause of morbidity and the second leading cause of mortality in individuals with cancers after disease progression.[1] Individuals with cancer have a 4-fold to 7-fold increased risk of VTE compared with the general population,[2,3,4] corresponding to 1 VTE event out of 200 individuals with active cancer annually.[5] Multiple factors are associated with risk of cancer-associated VTE, including tumor-associated factors (eg, cancer type and stage), treatment-associated factors (eg, major surgery, chemotherapy, antiangiogenic therapy, hormonal therapy, and central venous catheter use), and patient characteristics (eg, advanced age, obesity, and immobilization status).[6]. In the Randomized Comparison of Low-Molecular-Weight Heparin vs Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) clinical trial,[7] use of the low-molecular-weight heparin (LMWH) dalteparin reduced risk of VTE recurrence by 52%, with similar rates for major bleeding events, compared with use of oral vitamin K antagonist (VKA). After the publication of the CLOT study results, use of LMWH for at least 6 months has been recommended over the last decade as the standard of care for the acute treatment and secondary prophylaxis of VTE in patients with cancer.[8,9] continuous administration of LMWH over a course of several months is challenging because of its cost, inconvenience to patients, and adverse effects associated with subcutaneous injections, such as local pain and bruising.[10]

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