Dong-Yi Chen1,2, Chi-Nan Tseng3, Ming-Jer Hsieh1,2, Wen-Ching Lan4, Cheng-Keng Chuang5, See-Tong Pang5, Shao-Wei Chen3, Tien-Hsing Chen6, Shang-Hung Chang1,4, I-Chang Hsieh1, Pao-Hsien Chu1, Ming-Shien Wen1, Jen-Shi Chen7, John Wen-Cheng Chang7, Lai-Chu See8,9, Wen-Kuan Huang2,7,10. 1. Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. 2. Cardio-Oncology Program, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. 3. Department of Thoracic and Cardiovascular Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. 4. Center for Big Data Analytics and Statistics, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan. 5. Division of Urology, Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. 6. Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan. 7. Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan. 8. Department of Public Health, College of Medicine, Chang Gung University, Taoyuan, Taiwan. 9. Biostatistics Core Laboratory, Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan. 10. Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
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.
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 LMWHenoxaparin 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 LMWHenoxaparin. 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 LMWHenoxaparin. 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 LMWHenoxaparin. Nonetheless, use of a NOAC was associated with a significantly lower rate of gastrointestinal bleeding. Further prospective studies are needed to confirm these findings.
Authors: Dominique Farge; Corinne Frere; Jean M Connors; Cihan Ay; Alok A Khorana; Andres Munoz; Benjamin Brenner; Ajay Kakkar; Hanadi Rafii; Susan Solymoss; Dialina Brilhante; Manuel Monreal; Henri Bounameaux; Ingrid Pabinger; James Douketis Journal: Lancet Oncol Date: 2019-09-03 Impact factor: 41.316
Authors: Nigel S Key; Alok A Khorana; Nicole M Kuderer; Kari Bohlke; Agnes Y Y Lee; Juan I Arcelus; Sandra L Wong; Edward P Balaban; Christopher R Flowers; Charles W Francis; Leigh E Gates; Ajay K Kakkar; Mark N Levine; Howard A Liebman; Margaret A Tempero; Gary H Lyman; Anna Falanga Journal: J Clin Oncol Date: 2019-08-05 Impact factor: 44.544
Authors: Stavros V Konstantinides; Guy Meyer; Cecilia Becattini; Héctor Bueno; Geert-Jan Geersing; Veli-Pekka Harjola; Menno V Huisman; Marc Humbert; Catriona Sian Jennings; David Jiménez; Nils Kucher; Irene Marthe Lang; Mareike Lankeit; Roberto Lorusso; Lucia Mazzolai; Nicolas Meneveau; Fionnuala Ní Áinle; Paolo Prandoni; Piotr Pruszczyk; Marc Righini; Adam Torbicki; Eric Van Belle; José Luis Zamorano Journal: Eur Heart J Date: 2020-01-21 Impact factor: 35.855
Authors: Annie M Young; Andrea Marshall; Jenny Thirlwall; Oliver Chapman; Anand Lokare; Catherine Hill; Danielle Hale; Janet A Dunn; Gary H Lyman; Charles Hutchinson; Peter MacCallum; Ajay Kakkar; F D Richard Hobbs; Stavros Petrou; Jeremy Dale; Christopher J Poole; Anthony Maraveyas; Mark Levine Journal: J Clin Oncol Date: 2018-05-10 Impact factor: 44.544