Anticoagulation and Bleeding: A Pooled Analysis of Lung Cancer Trials of the NCIC Clinical Trials Group
Authors: Aurélie Le Maître, Keyue Ding, Frances A. Shepherd, Natasha Leighl, Andrew Arnold, Lesley Seymour
Journal: Journal of Thoracic Oncology (2009)

Background:Patients with cancer, including lung cancer are at an increased risk for venous thromboembolism and frequently are anticoagulated. Due to concerns of bleeding and drug-drug interactions, many clinical trials suggest the use of low-molecular-weight heparin (LMWH) rather than warfarin (coumadin) for patients requiring anticoagulation. We sought to evaluate, in a retrospective analysis, whether these recommendations were appropriate.Material/Methods:A pooled analysis of three lung cancer trials conducted by the NCIC Clinical Trials Group was performed to evaluate the risk of bleeding in patients receiving warfarin or LMWH; concomitant usage of nonsteroidal antinflammatories or aspirin. The Mantel-Haentzel test stratified by treatment group was used to analyze the prevalence of bleeding (all and ≥grade 3) according to LMWH, warfarin or nonsteroidal antiinflammatory drugs usage. Logistic regression was used to adjust for baseline characteristics including age, sex, performance status, creatinine, platelets.Results:Although bleeding was reported in a quarter of patients, only 2% experienced severe bleeding, with rates similar across the trials. In univariate analyses the risk of bleeding seemed higher with LMWH or warfarin usage, history of bleeding, thrombocytopenia, and increased age. However, in adjusted analyses only warfarin use was a significant risk factor (p = 0.073).Conclusions:In this retrospective analysis, warfarin seemed to increase the risk of bleeding in lung cancer patients enrolled in clinical trials. Current recommendations in many clinical trials to preferentially use LMWH seem appropriate. Patients with cancer, including lung cancer are at an increased risk for venous thromboembolism and frequently are anticoagulated. Due to concerns of bleeding and drug-drug interactions, many clinical trials suggest the use of low-molecular-weight heparin (LMWH) rather than warfarin (coumadin) for patients requiring anticoagulation. We sought to evaluate, in a retrospective analysis, whether these recommendations were appropriate. A pooled analysis of three lung cancer trials conducted by the NCIC Clinical Trials Group was performed to evaluate the risk of bleeding in patients receiving warfarin or LMWH; concomitant usage of nonsteroidal antinflammatories or aspirin. The Mantel-Haentzel test stratified by treatment group was used to analyze the prevalence of bleeding (all and ≥grade 3) according to LMWH, warfarin or nonsteroidal antiinflammatory drugs usage. Logistic regression was used to adjust for baseline characteristics including age, sex, performance status, creatinine, platelets. Although bleeding was reported in a quarter of patients, only 2% experienced severe bleeding, with rates similar across the trials. In univariate analyses the risk of bleeding seemed higher with LMWH or warfarin usage, history of bleeding, thrombocytopenia, and increased age. However, in adjusted analyses only warfarin use was a significant risk factor (p = 0.073). In this retrospective analysis, warfarin seemed to increase the risk of bleeding in lung cancer patients enrolled in clinical trials. Current recommendations in many clinical trials to preferentially use LMWH seem appropriate.