Clinical features and long-term outcomes of cancer-associated venous thromboembolism: transition from the warfarin era to the direct oral anticoagulant era

Abstract

Abstract Background/Introduction After the introduction of direct oral anticoagulant (DOAC) for venous thromboembolism (VTE), DOAC for VTE have prevailed all over the world. The usefulness of DOAC for cancer-associated VTE has also been recently reported and may change the daily clinical practice and clinical outcomes. However, there have been still limited data on the issue in the real world. Purpose We aimed to investigate the clinical characteristics, anticoagulation strategies, and long-term clinical outcomes of patients with cancer-associated VTE comparing a large observational study in the warfarin era and that in the DOAC era. Methods The COMMAND VTE Registry-1 (enrolled 3,027 VTE patients among 29 center between January 2010 and August 2014 in the warfarin era) and Registry-2 (enrolled 5,197 VTE patients among 31 centers between January 2015 and August 2020 in the DOAC era) are the series of a multicenter observational study in Japan enrolling consecutive patients with acute symptomatic VTE. In the present study, we evaluated patients with cancer-associated VTE of 695 cases from Registry-1 and 1507 cases from Registry-2. Results As for oral anticoagulation therapy, 83% (2,576/695) of patients were treated with warfarin in the Registry-1 and 80% (1,199/5,197) of patients were treated with DOAC in the Registry-2. Patients in the Registry-2 were slightly older (67±12 vs. 68±13 years, P=0.005), had a slightly higher body weight (55±12 vs. 57±13 kg, P=0.03), and more frequently had pulmonary embolism (44% vs. 49%, P=0.004). Patients in the Registry-2 were less frequently admitted to the hospital among those with out-of-hospital-onset VTE (83% vs. 66%, P<0.001), and median length of hospitalization was shorter in patients in the Registry-2 (16 [IQR: 11-26] vs. 14.5 [IQR: 9-24] days, P=0.01). AS for cancer types, lung cancer, colorectal cancer and stomach cancer were significantly higher in patients in the Registry-1 (18% vs. 15%, P=0.04; 14% vs. 10%, P=0.008; 9% vs. 6%, P=0.007). There was no significant difference in the discontinuation rate of anticoagulation therapy between the 2 groups (56.7% vs. 62.7% at 3-year, Log rank P=0.10). The cumulative 5-year incidence of recurrent VTE, major bleeding and all cause-death were significantly lower in patients in the Registry-2 (17.7% vs. 10.1%, P<0.001; 26.6% vs. 20.4%, P=0.045; 73.1% vs. 64.8%, P=0.003), while there were no significant differences in the cumulative 5-year incidences of intracranial bleeding (5.7% vs. 3.2%, P=0.056) nor major gastrointestinal bleeding between the 2 groups (13.9% vs. 10.1%, P=0.30) (Figure). Conclusion The introduction of DOAC for cancer-associated VTE could have a potential benefit of reducing the risk of recurrent VTE and major bleeding, although gastrointestinal bleeding might be still a major concerns even in the DOAC era.FigureFigure