@article{cbca6ef3eacc42b68e4522e87e66ee73,
title = "Clinically relevant bleeding in cancer patients treated for venous thromboembolism from the CATCH study",
abstract = "Essentials Cancer patients receiving anticoagulants for venous thromboembolism have an elevated bleeding risk. This secondary analysis of CATCH assessed characteristics of clinically relevant bleeding (CRB). CRB occurs in 15% of cancer patients with thrombosis using therapeutic doses of anticoagulation. After multivariate analysis, risk factors for CRB were age >75 years and intracranial malignancy. Summary: Background Cancer patients with acute venous thromboembolism (VTE) receiving anticoagulant treatment have an increased bleeding risk. Objectives We performed a prespecified secondary analysis of the randomized, open-label, Phase III CATCH trial (NCT01130025) to assess the rate and sites of and the risk factors for clinically relevant bleeding (CRB). Patients/Methods Patients with active cancer and acute, symptomatic VTE received either tinzaparin 175 IU kg−1 once daily or warfarin (target International Normalized Ratio [INR] of 2.0–3.0) for 6 months. Fisher's exact test was used to screen prespecified clinical risk factors; those identified as being significantly associated with an increased risk of CRB then underwent competing risk regression analysis of time to first CRB. Results Among 900 randomized patients, 138 (15.3%) had 180 CRB events. CRB occurred in 60 patients (81 events) in the tinzaparin group and in 78 patients (99 events) in the warfarin group (hazard ratio [HR] 0.64; 95% confidence interval [CI] 0.45–0.89). Common bleeding sites were gastrointestinal (36.7%; n = 66), genitourinary (22.8%; n = 41), and nasal (10.0%; n = 18). In multivariate analysis, the risk of CRB increased with age > 75 years (HR 1.83, 95% CI 1.14–2.94) and intracranial malignancy (HR 1.97, 95% CI 1.07–3.62). In the warfarin group, 40.4% of CRB events occurred in patients with with an INR of < 3.0. A lower time in therapeutic range was associated with a higher risk of CRB. Conclusions CRB is a frequent complication in cancer patients with VTE during anticoagulant treatment, and is associated with age > 75 years and intracranial malignancy.",
keywords = "anticoagulants, bleeding, neoplasms, tinzaparin, venous thromboembolism",
author = "{the CATCH Investigators} and Kamphuisen, {P. W.} and Lee, {A. Y.Y.} and G. Meyer and R. Bauersachs and Janas, {M. S.} and Jarner, {M. F.} and Khorana, {A. A.} and {Bella Santiago}, R. and S. Cerana and Zarb{\'a}, {J. J.} and J. Andel and Barrios, {C. H.} and {Borba Reiriz}, A. and F. Cesario and {de Azevedo}, S. and {Ferreira Filho}, {A. F.} and Franke, {F. A.} and S. Padilha and {Paiva Queiroz}, R. and A. Pimenta and J. Rerin and R. Rigo and {van Eyll Rocha}, {S. B.} and {Santos Borges}, G. and G. Vacaro and V. Anastasov and T. Dragneva and G. Georgiev and P. Champion and P. Kuruvilla and C. Gonzalez and P. Ditl and J. F{\"o}rster and B. Lubomir and J. Vydra and {El Hassan}, {R. A.} and S. Sabri and N. Allahloubi and A. Elzawawy and Ezzat, {S. S.} and {El Kady}, {M. S.} and L. Bacchus and J. Beyer-Westendorf and U. Kamphausen and D. Niederwieser and H. Ostermann and M. Sosada and N. Anagnostopoulos and G. Fountzilas and R. Naik",
note = "Funding Information: P. W. Kamphuisen has received honoraria from LEO Pharma, and has received research funding from Boehringer Ingelheim, Pfizer, and Daichi Sankyo. A. Y. Y. Lee has received research funding from Bristol-Myers Squibb, and has received honoraria from and acted as a consultant for LEO Pharma and Pfizer. G. Meyer has received research funding from Bayer, Boehringer Ingelheim, and LEO Pharma, and has received travel, accommodation or other expenses from Pfizer, Daiichi Sankyo, and Bayer. R. Bauersachs has received honoraria from and acted as a consultant for Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, LEO Pharma, and Pfizer. M. S. Janas and M. F. Jarner are employed by LEO Pharma. A. A. Khorana has received research funding from LEO Pharma and Amgen (Inst), has received honoraria from and acted as a consultant for Sanofi, LEO Pharma, AngioDynamics, Daiichi Sankyo, Genentech, Janssen Pharmaceuticals, Boehringer Ingelheim, Halo-zyme, and Bayer, and has received travel, accommodation or other expenses from Janssen Pharmaceuticals, AngioDynamics, Halozyme, and Pfizer. Funding Information: M. Burns from Mudskipper Business Limited, funded by LEO Pharma A/S, provided formatting and editorial assistance. J. Cassidy was a member of the Steering Committee until June 2011. L. Paz-Ares Rodriguez was a member of the Steering Committee from September to November 2012. Neither was involved with data analysis, data interpretation, or any publication of the trial results. Central Adjudication members were: M. Prins (Chairman), Academic Hospital Maastricht, Maastricht, the Netherlands. Funding Information: M. Burns from Mudskipper Business Limited, funded by LEO Pharma A/S, provided formatting and editorial assistance. Publisher Copyright: {\textcopyright} 2018 International Society on Thrombosis and Haemostasis",
year = "2018",
month = jun,
doi = "10.1111/jth.14007",
language = "English (US)",
volume = "16",
pages = "1069--1077",
journal = "Journal of Thrombosis and Haemostasis",
issn = "1538-7933",
publisher = "Wiley-Blackwell",
number = "6",
}