Risks of recurrence and treatment-emergent bleeding are high in patients with cancer-associated venous thromboembolism (VTE) but factors associated with these risks remain substantially undefined... Show moreRisks of recurrence and treatment-emergent bleeding are high in patients with cancer-associated venous thromboembolism (VTE) but factors associated with these risks remain substantially undefined.The aim of this analysis in patients with cancer-associated VTE included in the Caravaggio study was to identify risk factors for recurrent VTE and major bleeding. Variables potentially predictive for recurrent VTE or major bleeding were evaluated in a Cox proportional hazard multivariable analysis with backward variable selection.Recurrent VTE occurred in 78 patients (6.8%) and major bleeding in 45 (3.9%). Independent risk factors for recurrent VTE were deep vein thrombosis (DVT) as index event (Hazard ratio (HR) 1.84, 95% CI 1.17–2.88), ECOG status of 1 or more (HR 1.95, 95% CI 1.11–3.43), pancreatic or hepatobiliary cancer site (HR 2.20, 95% CI 1.19–4.06), concomitant anti-cancer treatment (HR 1.98, 95% CI 1.03–3.81) and creatinine clearance (HR 1.10, 95% CI 1.00–1.20 for every 10 ml/min absolute increase). Independent risk factors for major bleeding were ECOG status of 2 (HR 2.31, 95% CI 1.24–4.29), genitourinary cancer site (HR 2.72, 95% CI 1.28–5.77), upper gastrointestinal cancer site (HR 3.17, 95% CI 1.22–8.23), and non-resected luminal gastrointestinal cancer (HR 2.77, 95% CI 1.38–5.56).This analysis of the Caravaggio study in patients with cancer-associated VTE who were on standardized anticoagulant treatment identified five independent predictors for recurrent VTE and four independent predictors of treatment-emergent major bleeding. Considering these risks could help clinicians to optimize the anticoagulant treatment in patients with cancer-associated VTE. Show less
Verso, M.; Agnelli, G.; Munoz, A.; Connors, J.M.; Sanchez, O.; Huisman, M.; ... ; Becattini, C. 2022
Background: Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the... Show moreBackground: Patients with cancer-associated venous thromboembolism (VTE) have a high risk of VTE recurrence and anticoagulant treatment-related bleeding, but the correlation of these risks with the cancer stage is unclear.Methods: We evaluated the risks of VTE recurrence and treatment-related major bleeding according to the cancer stage in patients with VTE and solid cancer randomised to apixaban or dalteparin in the Caravaggio study. Cancer stage was categorised by expert cancer physicians according to pre-specified criteria, and study outcomes were adjudicated by an independent committee unaware of cancer stage and treatment allocation.Results: Of the 1034 patients included in this analysis, 217 (21.0%) had localised cancer, 279 (27.0%) locally advanced cancer and 503 (48.7%) metastatic cancer. Cancer stage was undetermined in 35 patients (3.4%). VTE recurrence and major bleeding rates were 2.8% and 3.2% in patients with localised cancer, respectively. In comparison to patients with localised cancer, the VTE recurrence rate was higher in patients with locally advanced cancer (7.5%, hazard ra-tio [HR] = 2.8, 95% confidence interval [CI] = 1.1-6.9) and metastatic cancer (8.7%, HR = 3.3, CI = 1.4-7.7, CI). Patients with metastatic cancer had numerically increased major bleedings compared to those with localised cancer (5.2%, HR = 1.65, CI = 0.7-3.8). The ef-ficacy and safety of apixaban and dalteparin across patients with different cancer stages were consistent with the findings observed in the overall patients with cancer randomised in the study.Conclusions: Patients with locally advanced and metastatic cancer have a higher rate of VTE recurrence than patients with localised cancer with no statistically significant difference in treatment-related major bleeding. (c) 2022 Published by Elsevier Ltd. Show less
Verso, M.; Munoz, A.; Bauersachs, R.; Huisman, M.V.; Mandala, M.; Vescovo, G.; ... ; Agnelli, G. 2021
Background: Whether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism (VTE)... Show moreBackground: Whether concomitant administration of anticancer agents influences the efficacy and safety of oral anticoagulants in patients treated for cancer-associated venous thromboembolism (VTE) is undefined. The pharmacological interaction between anticancer agents and direct oral anticoagulants is perceived as a concern.Methods: We evaluated the effects of concomitant administration of anticancer agents on recurrent VTE, major bleeding and death in patients with cancer-associated VTE randomised to receive apixaban or dalteparin in the Caravaggio study.Results: Anticancer agents were concomitantly given to 336 patients (58.3%) treated with apixaban and to 332 patients (57.3%) treated with dalteparin. In patients treated with apixaban, recurrent VTE occurred in 20 (6.0%) and 12 (5.0%) among patients treated or not treated with anticancer agents, respectively (hazard ratio [HR] = 1.14; 0.55-2.38); major bleeding occurred in 12 (3.6%) and 10 (4.2%) patients , respectively (HR = 0.79; 0.34-1.82), and death occurred in 74 (22.0%) and 61 (25.4%) patients , respectively (HR = 0.71; 0.51-1. 00). In patients treated with dalteparin, recurrent VTE occurred in 24 (7.2%) and 22 (8.9%) among patients treated or not treated with anticancer agents, respectively (HR = 0.71; 0.40-1.28); major bleeding occurred in 16 (4.8%) and 7 (2.8%) patients, respectively (HR = 1.78; 0.66-4.79 ), and death occurred in 87 (26.2% ) and 66 (26.7 %) patients, respectively (HR = 0.85; 0.62-1.18). The comparative efficacy and safety of apixaban and dalteparin was not different in patients treated or not treated with anticancer agents. No effect on recurrent VTE, major bleeding or death was observed with inhibitors or inducers of P-glycoprotein and/or CYP3A4.Conclusion: In our study, concomitant administration of anticancer agents had no effect on the risk of VTE recurrence or major bleeding in patients treated with apixaban or dalteparin for cancer-associated VTE.(c) 2021 Elsevier Ltd. All rights reserved. Show less
