Safety and effectiveness of initial high-dose anticoagulation therapy for cancer-associated venous thromboembolism in the real world: insight from the COMMAND VTE Registry-2

Abstract

Abstract Background/Introduction Initial high-dose anticoagulation therapy by rivaroxaban and apixaban has been a standard treatment for venous thromboembolism (VTE), although there could be concerns of bleeding especially among high bleeding-risk patients including those with active cancer. However, there is limited data on the issue comparing those with and without initial high-dose anticoagulation therapy. Purpose The present study aimed to examine the safety and effectiveness of initial high-dose anticoagulation therapy in patients with cancer-associated VTE. Methods The COMMAND VTE Registry-2 is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020. The present study population was consisted of 1507 patients with cancer-associated VTE. We compared the patient characteristics and clinical outcomes between patients with initial high-dose anticoagulation therapy and those without. Results Patients with initial high-dose anticoagulation therapy and those without accounted for 344 (23%) and 1163 (77%) patients, respectively. Of patients with initial high-dose anticoagulation therapy, rivaroxaban and apixaban were administered in 210 and 134 patients, respectively, whereas, of those without, direct oral anticoagulant (DOAC), warfarin and other therapies were administered in 855, 164 and 144 patients, respectively. Patients with initial high-dose anticoagulation therapy were younger (66±12 vs. 79±13 years, P=0.002), had a higher body weight (59±13 vs. 56±12 kg, P=0.001), more frequently had pulmonary embolism (61% vs. 48%, P<0.001), and less frequently had chronic kidney disease (11% vs. 21%, P<0.001), anemia (70% vs. 79%, P<0.001) and terminal cancer (7% vs. 17%, P<0.001). The mean of durations of initial high-dose anticoagulation therapy were 18±8 days for rivaroxaban and 7±1 days for apixaban. There was no significant difference in the distribution of gastrointestinal cancer such as esophageal, stomach and colorectal cancer between the 2 groups (1.2% vs. 1.8%, P=0.63, 4.9% vs. 5.7%, P=0.69, 8.1% vs. 10.7%, P=0.19). The cumulative 180-day incidence of all cause-death was significantly lower in patients with initial high-dose anticoagulation therapy (23.6% vs. 34.7%, P<0.001), while there were no significant differences in the cumulative 180-day incidences of recurrent VTE (4.3% vs. 3.1%, P=0.30) nor major bleeding (8.3% vs. 10.1%, P=0.35) between the 2 groups. There were also no significant differences in the cumulative 180-day incidences of all bleeding (15.4% vs. 16.8%, P=0.43), gastrointestinal (GI) bleeding (9.1% vs. 8.2%, P=0.61), nor major GI bleeding (5.5% vs. 4.9%, P=0.70) (Figure). Conclusions In the real-world clinical practice, initial high-dose anticoagulation therapy for cancer-associated VTE seemed to be more frequently administered for low bleeding-risk patients and did not show a higher risk of bleeding including gastrointestinal bleeding.FigureFigure