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Introduction: Low-molecular-weight heparin (LMWH) and vitamin K antagonists (VKA) are current treatment options for cancer patients suffering from acute venous thromboembolism (VTE). The role of direct-acting oral anticoagulants (DOACs) for the treatment of VTE in cancer patients, particular in comparison with the current standard of care which is LMWH, remains unclear. In this network meta-analysis, we compared the relative efficacy and safety of LMWH, VKA, and DOAC for the treatment of cancer-associated VTE., Methods: A pre-specified search protocol identified 10 randomized controlled trials including 3242 cancer patients. Relative risks (RR) of recurrent VTE (efficacy) and major bleeding (safety) were analyzed using a random-effects meta-regression model., Results: LMWH emerged as significantly superior to VKA with respect to risk reduction of recurrent VTE (RR=0.60, 95%CI:0.45-0.79, p<0.001), and its safety was comparable to VKA (RR=1.08, 95%CI:0.70-1.66, p=0.74). For the DOAC vs. VKA efficacy and safety comparison, the relative risk estimates were in favor of DOAC, but had confidence intervals that still included equivalence (RR for recurrent VTE=0.65, 95%CI:0.38-1.09, p=0.10; RR for major bleeding=0.72, 95%CI:0.39-1.37, p=0.32). In the indirect network comparison between DOAC and LMWH, the results indicated comparable efficacy (RR=1.08, 95%CI:0.59-1.95, p=0.81), and a non-significant relative risk towards improved safety with DOAC (RR=0.67, 95%CI:0.31-1.46, p=0.31). The results prevailed after adjusting for different risk of recurrent VTE and major bleeding between LMWH vs. VKA and DOAC vs. VKA studies., Conclusion: The efficacy and safety of LMWH and DOACs for the treatment of VTE in cancer patients may be comparable., Funding: Austrian Science Fund (FWF-SFB-54)., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Introduction: Patients with cancer are at risk of venous thromboembolism (VTE). Statin-use has been shown to be associated with low risk of VTE in patients without cancer, but data in cancer patients is scarce. The objective of this study was to evaluate the association of statins with risk of VTE in cancer patients in a prospective observational cohort study., Materials and Methods: Patients with newly diagnosed cancer or progression of disease after remission were included and prospectively followed for a maximum of 2 years. Study endpoint was occurrence of symptomatic VTE., Results: Patients (n=1434) were followed over a median observation period of 729 days. VTE occurred in 107 (7.5%) patients. At study inclusion, 170 (11.9%) patients took statins. Simvastatin (n=96) and atorvastatin (n=48) were the most frequently prescribed statins. VTE occurred in 6 (3.5%) patients with statins. Patients with statins had a lower risk of VTE than patients without (subhazard ratio 0.43, 95% confidence interval 0.19 to 0.98; p=0.04). In competing risk analysis, the cumulative probability of VTE in patients with statins was 2.94% after 12 months and 3.54% after 24 months, compared to 7.13% and 8.13% in the group without statins (Gray's test: p=0.04)., Conclusion: This study provides observational evidence for an association between statin use and low risk of VTE in patients with cancer. The role of statins for prevention of cancer-associated VTE needs to be confirmed in randomized, controlled trials., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Introduction: The risk for occurrence of venous thromboembolism (VTE) in cancer patients has been the aim of numerous investigations. Chronic kidney disease (CKD) is a frequent comorbidity in cancer patients and has been found to be a risk factor for VTE in the general population. We investigated the association of CKD with VTE and mortality in cancer patients., Methods: Patients were recruited into the prospective cohort study, Vienna Cancer and Thrombosis Study (CATS). CKD was estimated with equations for glomerular filtration rate (eGFR) based on serum creatinine by Modification of Diet in Renal Disease (MDRD), CKD Epidemiology collaboration (CKD-EPI) and Cockcroft-Gault equation (C-G). Patients were subsequently classified to stages of CKD according to the Kidney Diseases Outcomes Quality Initiative. Primary endpoint was occurrence of VTE and secondary endpoint was death., Results: The cohort of 1100 patients was prospectively followed over a median of 723 days. CKD with an eGFR of under 90 ml/min was common with a prevalence of 71.1%, 67.0% or 51.5% of patients calculated with MDRD, CKD-EPI and C-G equations, respectively, but severe CKD (eGFR<30 ml/min) was rare. Patients with a moderately decreased eGFR (90-60 ml/min/1.73 m(2)) based on CKD-EPI had a subdistribution hazard ratio of 0.68 (95% confidence interval 0.43-1.06). An association between CKD and occurrence of VTE or mortality could also not be shown with the other equations., Conclusions: In our investigation of a large cohort of cancer patients with a high prevalence of CKD, a reduced eGFR was not an independent risk factor for occurrence of VTE or death., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: Brain tumor patients have an increased risk of venous thromboembolism (VTE). An important role in cancer-related VTE has been suggested for tissue factor (TF), the main initiator of the coagulation cascade. We conducted a prospective cohort study to determine whether expression levels of TF in brain tumors are associated with future VTE., Patients and Methods: We immunohistochemically determined TF-expression in brain tumor specimens of 96 adult patients (8 low-grade and 82 high-grade gliomas, 6 embryonal tumors) that were included in the Vienna Cancer and Thrombosis Study (CATS). Each patient was prospectively followed until the occurrence of VTE and/or death within a period of two years or loss of follow-up., Results: Fifteen brain tumor patients (15.6%) developed VTE during follow-up. Seventy-seven brain tumors (80.2%) stained positive for TF. Staining was strong in 13 (13.5%), moderate in 64 (66.7%) and negative in 19 (19.8%) tumors. No statistically significant association between TF-expression (negative, focal, widespread) and the occurrence of VTE was found. The hazard ratio (HR) for VTE was 1.30 (95% confidence interval [CI]: 054 - 3.14, p=0.567) when patients with negative-, focal- and widespread TF expression were compared and not statistically significant. Also when tumors were categorized into two groups (focal/widespread versus negative TF-expression), the HR for future VTE was not statistically significant (HR: 1.45, 95% CI: 0.44 - 7.37; p=0.578). An association can still not be definitely excluded, as this study was underpowered., Conclusions: Our data indicate that TF-expression levels in brain tumors are not strongly associated with future VTE., (Copyright © 2012 Elsevier Ltd. All rights reserved.)