Antonios Douros1, Christopher Filliter2, Laurent Azoulay3, Vicky Tagalakis4. 1. Department of Medicine, McGill University, Montreal, QC, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada; Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, QC, Canada; Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Berlin, Germany. 2. Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, QC, Canada. 3. Department of Medicine, McGill University, Montreal, QC, Canada; Centre for Clinical Epidemiology, Lady Davis Institute, Montreal, QC, Canada; Gerald Bronfman Department of Oncology, McGill University, Montreal, QC, Canada. 4. Department of Medicine, McGill University, Montreal, QC, Canada; Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, QC, Canada; Division of General Internal Medicine, Jewish General Hospital, Montreal, QC, Canada. Electronic address: vicky.tagalakis@mcgill.ca.
Abstract
INTRODUCTION: Real-world evidence on the effects of direct oral anticoagulants (DOACs) in patients with cancer associated venous thromboembolism (VTE) is limited. Thus, our population-based cohort study aimed to assess the effectiveness and safety of DOACs compared to the standard of care low-molecular-weight heparin (LMWH) in this vulnerable population. MATERIALS AND METHODS: Using linked administrative healthcare databases from the province of Québec, Canada, we identified patients with incident VTE from 2012 to 2015 and a cancer diagnosis in the year before the VTE, who initiated treatment with anticoagulants within 30 days after the VTE. Using an active comparator new-user design with an as-treated exposure definition, we compared use of DOACs with use of LMWH. Cox proportional hazards models estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of recurrent VTE, major bleeding, and all-cause mortality. In secondary analyses, we stratified by age and sex. RESULTS: Overall, 4438 patients with cancer associated VTE initiated treatment with anticoagulants (513 DOACs, 2698 LMWH). During a median follow-up of 0.3 years, and compared with LMWH, DOACs were associated with a decreased risk of recurrent VTE (HR, 0.54; 95% CI, 0.36-0.82) and major bleeding (HR, 0.54; 95% CI, 0.31-0.96). We also observed a decreased risk of all-cause mortality with DOACs compared with LMWH (HR, 0.14; 95% CI, 0.09-0.22). Age and sex did not modify the associations. CONCLUSIONS: DOACs were associated with improved effectiveness and safety compared with LMWH in patients with cancer related VTE. Unmeasured confounding probably contributed to our findings on all-cause mortality.
INTRODUCTION: Real-world evidence on the effects of direct oral anticoagulants (DOACs) in patients with cancer associated venous thromboembolism (VTE) is limited. Thus, our population-based cohort study aimed to assess the effectiveness and safety of DOACs compared to the standard of care low-molecular-weight heparin (LMWH) in this vulnerable population. MATERIALS AND METHODS: Using linked administrative healthcare databases from the province of Québec, Canada, we identified patients with incident VTE from 2012 to 2015 and a cancer diagnosis in the year before the VTE, who initiated treatment with anticoagulants within 30 days after the VTE. Using an active comparator new-user design with an as-treated exposure definition, we compared use of DOACs with use of LMWH. Cox proportional hazards models estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of recurrent VTE, major bleeding, and all-cause mortality. In secondary analyses, we stratified by age and sex. RESULTS: Overall, 4438 patients with cancer associated VTE initiated treatment with anticoagulants (513 DOACs, 2698 LMWH). During a median follow-up of 0.3 years, and compared with LMWH, DOACs were associated with a decreased risk of recurrent VTE (HR, 0.54; 95% CI, 0.36-0.82) and major bleeding (HR, 0.54; 95% CI, 0.31-0.96). We also observed a decreased risk of all-cause mortality with DOACs compared with LMWH (HR, 0.14; 95% CI, 0.09-0.22). Age and sex did not modify the associations. CONCLUSIONS:DOACs were associated with improved effectiveness and safety compared with LMWH in patients with cancer related VTE. Unmeasured confounding probably contributed to our findings on all-cause mortality.