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

Abstract

Importance: 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).

Objective: 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.

Design, setting, and participants: 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.

Exposures: Receiving a NOAC (including rivaroxaban, apixaban, edoxaban, or dabigatran) or the LMWH enoxaparin.

Main outcomes and measures: 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.

Results: 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).

Conclusions and relevance: 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.

Figure 1.. Cumulative Probability of Event Rates

Figure 2.. Composite Outcomes of Recurrent Venous Thromboembolism (VTE) and Major Bleeding by Subgroup

NOAC indicates non–vitamin K antagonist oral anticoagulant; LMWH, low-molecular-weight heparin; GI, gastrointestinal; HR, hazard ratio. To convert hemoglobin to grams per liter, multiply by 10.0; and platelet count to ×10⁹ per liter, multiply by 1.0.

Figure 3.. Cumulative Incidence of Recurrent VTE or Major Bleeding at 1-Year Follow-up by NOAC Subtype

VTE indicates venous thromboembolism; NOAC, non–vitamin K antagonist oral anticoagulant.