Direct oral anticoagulants in patients with liver cirrhosis: A systematic review

Introduction: Anticoagulant treatment in patients with liver cirrhosis is challenging. The aim of this systematic review was to evaluate clinical outcomes of direct oral anticoagulant (DOAC) therapy in cirrhosis patients. Materials and methods: A systematic search was performed in MEDLINE, Embase, and conference proceedings up to November 7th, 2017, for studies that evaluated the efficacy and safety of DOACs in cirrhosis patients with venous thromboembolism (VTE), splanchnic vein thrombosis (SVT), or atrial fibrillation (AF). Two authors independently screened titles, abstracts, and full-text articles, and assessed risk of bias. A meta-analysis could not be performed due to heterogeneity of the included studies. Results: Of the 2927 articles assessed, five retrospective cohort studies were included (n = 239, including 20 patients overlap). All studies had fair methodological quality. Two studies evaluated DOAC treatment only, and three also evaluated vitamin K antagonists (VKAs) or low-molecular-weight heparins (LMWHs). Recurrent VTE (DOAC n = 12, LMWH/VKA n = 8) or ischemic stroke (DOAC n = 37, LMWH/VKA n = 9) occurred in none of the patients. Progression of VTE was 8% with DOACs (n = 12) and 13% with VKAs and LWWH (n = 8). Recurrent SVT occurred in 0 to 4% with DOACs (n = 31). Progression of SVT was 0 to 5% with DOACs (n = 24) and 0 to 47% with VKAs and LMWH (n = 33). Major bleeding risk ranged from 4 to 15% with DOACs (n = 172) and from 7 to 28% with VKAs and LMWH (n = 67). All-cause mortality risk was 6% with DOACs (n = 36). Conclusions: There is paucity of data on the efficacy and safety of DOACs in patients with cirrhosis. This analysis suggests that DOACs may be effective and safe for treatment of VTE, SVT, and AF in these patients

Safety of anticoagulant treatment in cancer patients

Patients with cancer are at increased risk of (recurrent) venous thromboembolism. They are also at increased risk of bleeding. This makes treatment of venous thromboembolisms (VTE) in cancer patients challenging. In this review, we will focus on the safety of anticoagulant treatment of VTE in cancer patients. We will discuss the absolute and relative bleeding risks associated with the various types of anticoagulants, specifically focusing on low-molecular-weight heparins (LMWH), vitamin K antagonist (VKA) and the new oral anticoagulants (NOACs). Monotherapy with LMWH is recommended for treatment of acute VTE in cancer patients. The bleeding risk associated with LMWH is comparable to VKAs, but LMWH are more effective in preventing recurrent VTE. More evidence on the efficacy and safety of NOACs in cancer patients is neede

A clinical prediction model for cancer-associated venous thromboembolism: a development and validation study in two independent prospective cohorts

Background: Venous thromboembolism is a common complication of cancer, but the risk of developing venous thromboembolism varies greatly among individuals and depends on numerous factors, including type of cancer. We aimed to develop and externally validate a clinical prediction model for cancer-associated venous thromboembolism. Methods: We used data from the prospective Vienna Cancer and Thrombosis Study (CATS) cohort (n=1423) to select prognostic variables for inclusion in the model. We then validated the model in the prospective Multinational Cohort Study to Identify Cancer Patients at High Risk of Venous Thromboembolism (MICA) cohort (n=832). We calculated c-indices to show how the predicted incidence of objectively confirmed venous thromboembolism at 6 months compared with the cumulative 6-month incidences observed in both cohorts. Findings: Two variables were selected for inclusion in the final clinical prediction model: tumour-site risk category (low or intermediate vs high vs very high) and continuous D-dimer concentrations. The multivariable subdistribution hazard ratios were 1·96 (95% CI 1·41–2·72; p=0·0001) for high or very high versus low or intermediate and 1·32 (95% CI 1·12–1·56; p=0·001) per doubling of D-dimer concentration. The cross-validated c-indices of the final model were 0·66 (95% CI 0·63–0·67) in CATS and 0·68 (0·62–0·74) in MICA. The clinical prediction model was adequately calibrated in both cohorts. Interpretation: An externally validated clinical prediction model incorporating only one clinical factor (tumour-site category) and one biomarker (D-dimer) predicted the risk of venous thromboembolism in ambulatory patients with solid cancers. This simple model is a considerable improvement on previous models for predicting cancer-associated venous thromboembolism, and could aid physicians in selection of patients who will likely benefit from thromboprophylaxis. Funding: Austrian Science Fund, Austrian National Bank Memorial Fund, and participating hospitals

Fondaparinux or Enoxaparin for the initial treatment of symptomatic deep venous thrombosis - A randomized trial

Background: The current standard initial therapies for deep venous thrombosis are low-molecular-weight heparin and unfractionated heparin. In a dose-ranging study of patients with symptomatic deep venous thrombosis, fondaparinux had efficacy and a safety profile similar to those of low-molecular-weight heparin (dalteparin). Objective: To evaluate whether fondaparinux has efficacy and safety similar to those of enoxaparin in patients with deep venous thrombosis. Design: Randomized, double-blind study. Setting: 154 centers worldwide. Patients: 2205 patients with acute symptomatic deep venous thrombosis. Intervention: Fondaparinux, 7.5 mg (5.0 mg in patients weighing 100 kg) subcutaneously once daily, or enoxaparin, 1 mg/kg of body weight, subcutaneously twice daily for at least 5 days and until vitamin K antagonists induced an international normalized ratio greater than 2.0. Measurements: The primary efficacy outcome was the 3-month incidence of symptomatic recurrent venous thromboembolic complications. The main safety outcomes were major bleeding during initial treatment and death. An independent, blinded committee adjudicated all outcomes. Results: 43 (3.9%) of 1098 patients randomly assigned to fondaparinux had recurrent thromboembolic events compared with 45 (4.1%) of 1107 patients randomly assigned to enoxaparin (absolute difference, -0.15 percentage point [95% Cl, -1.8 to 1.5 percentage points]). Major bleeding occurred in 1.1% of patients receiving fondaparinux and 1.2% of patients receiving enoxaparin. Mortality rates were 3.8% and 3.0%, respectively. Limitations: Follow-up was incomplete in 0.4% of fondaparinux-treated patients and 1.0% of enoxaparin-treated patients. Conclusions: Once-daily subcutaneous fondaparinux was at least as effective (not inferior) and safe as twice-daily, body weight-adjusted enoxaparin in the initial treatment of patients with symptomatic deep venous thrombosi

Edoxaban for venous thromboembolism in patients with cancer: results from a non-inferiority subgroup analysis of the Hokusai-VTE randomised, double-blind, double-dummy trial

International audienc