Impact of anticoagulant choice on hospitalized bleeding risk when treating cancer-associated venous thromboembolism

• Type of Material: Article
• Authors: Neil A. Zakai, University of Vermont; Rob F. Walker, University of Minnesota; Richard F. MacLehose, University of Minnesota; Terrence J. Adam, University of Minnesota; Alvaro Alonso, Emory University; Pamela L. Lutsey, University of Minnesota
• Language: English
• Date: 2018-12-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018 International Society on Thrombosis and Haemostasis
• Final Published Version (URL): http://dx.doi.org/10.1111/jth.14303
• Title of Journal or Parent Work: Journal of Thrombosis and Haemostasis
• ISSN: 1538-7933
• Volume: 16
• Issue: 12
• Start Page: 2403
• End Page: 2412
• Grant/Funding Information: This study was funded by grants R01-HL122200 (PI Alonso) and R01HL131579 (P. L. Lutsey) from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD.
• Keywords: neoplasms; EFFICACY; ORAL ANTICOAGULANTS; EDOXABAN; METAANALYSIS; SAFETY; drug utilization; Cardiovascular System & Cardiology; hemorrhage; ACCURACY; venous thrombosis; Science & Technology; CODES; THERAPY; Life Sciences & Biomedicine; Peripheral Vascular Disease; Hematology; THROMBOSIS; CLAIMS DATA; anticoagulants
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology

Abstract

Background: Direct acting oral anticoagulants (DOACs) are associated with less bleeding than traditional venous thromboembolism (VTE) treatments in the general population but are little studied in cancer-associated VTE (CA-VTE). Objective: To determine whether different anticoagulation strategies for CA-VTE have different hospitalized bleeding rates. Patients/Methods: We conducted a retrospective study of patients with CA-VTE, diagnosed between 2011 and 2015, in a large administrative database. Using validated algorithms, we identified 26 894 CA-VTE patients treated with anticoagulants and followed them for hospitalized severe bleeding. Cox models were used to assess bleeding risk, adjusted for age, sex, high dimensional propensity score and frailty. Results: Over 27 281 person-years of follow-up (median 0.6 years), 1204 bleeding events occurred, for a bleeding rate of 4.4% per patient-year. Bleeding rates varied by cancer type, with the highest rate for upper gastrointestinal cancers (8.6%) and the lowest for breast cancer (2.9%). In Cox models (hazard ratio [HR]; 95% confidence interval [CI]), compared with warfarin, DOACS and low-molecular-weight heparin (LMWH) had similar hazards of bleeding (HR, 0.88; 95% CI, 0.69–1.11 and 0.98; 0.85–1.13). Compared with LMWH, there was no difference in hazard of bleeding with DOACs (0.86; 0.66–1.12). There was heterogeneity in bleeding risk with DOACs by cancer type, with a higher risk of bleeding in upper gastrointestinal cancers and lower risk of bleeding in prostate cancer and hematologic cancers. Conclusions: In this practice-based sample of CA-VTE patients, DOACs were associated with similar bleeding risks to warfarin and LMWH. These findings suggest a complex association of bleeding risk with anticoagulant choice in cancer patients.