Safety and Effectiveness of Non-vitamin K Antagonist Oral Anticoagulants in Fragile Patients with Venous Thromboembolism

Introduction, Objectives, and/or Purpose: 1. Compare the bleeding complications associated with the use of non-vitamin K antagonist oral anticoagulants (NOACs) in fragile patients, including those with cancer, chronic kidney disease (CKD), or old age.
2. Evaluate the safety of NOACs in the aforementioned patient populations.

Methods: Using hospital data from 2013 to 2019, we compared the risk of intracranial hemorrhage (ICH), gastrointestinal (GI) bleeding, transfusion for major bleeding, and all-cause in patients with VTE who were naïve to NOAC (n=12,369) and warfarin (n=4,123). Hazard ratios for the clinical outcomes were analyzed using Cox regression analysis with warfarin as the reference. The institutional ethics review board approved this cohort study (2020-1923) and waived informed consent because of retrospective nature of this study.

Results: A total of 4,122 patients were found eligible for study entry. Mean (SD) age at index was 62.5 [15.1] years. Patients who had treatment with a NOAC were 3,020 (74.1%) and with a warfarin were 1,058 patients (25.9%). Recurrent VTE or major bleeding occurred in 168 patients (5.6%) treated with NOAC and 70 patients (6.6%) treated with warfarin ((HR, 0.964; 95%CI, 0.728–1.277; P = .799). There were 96 patients (3.2%) in the NOAC group and 23 patients (2.2%) in the warfarin group who met the effectiveness outcome of recurrent VTE, with increased risk (HR, 1.776; 95%CI, 1.123–2.808; P = .014). Incidence rate per 100 person-year was also significantly higher in the NOAC group (p < 0.001). There were 74 patients (2.5%) in the NOAC group and 52 patients (4.9%) in the warfarin with non-major and major bleeding events, with significantly lower risk in the NOAC group (HR, 0.562; 95%CI, 0.393-0.805; P = .002). Most common bleeding site was gastrointestinal tract in both groups (38 patients [51.4%.] in the NOAC group and 29 patients [55.8%] in the warfarin group). Risks for combined recurrent VTE and bleeding was not significantly different between the all subgroup (all, P>0.05). In patients under age of 80, without cancer or without dialysis, patients treated with NOACs had a higher risk of recurrent VTE (p < 0.05). Bleeding risk was significantly lower in patients treated with NOACs when under age of 80 or body weight over 60kg (p < 0.05). Regardless presence of cancer, bleeding risk was lower in patients treated with NOACs.

Conclusion(s): NOAC showed comparable or favorable safety compared to warfarin in fragile patient population.