Direct oral anticoagulants in cirrhosis: Rationale and current evidence

Pereira Portela, Cindy; Gautier, Lucas A.; Zermatten, Maxime G.; Fraga, Montserrat; Moradpour, Darius; Bertaggia Calderara, Debora; Aliotta, Alessandro; Veuthey, Lucas; De Gottardi, Andrea; Stirnimann, Guido; Alberio, Lorenzo

doi:10.1016/j.jhepr.2024.101116

JHEP Reports

2024

DOI: 10.1016/j.jhepr.2024.101116

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Direct oral anticoagulants in cirrhosis: Rationale and current evidence

Cindy Pereira Portela,

Lucas A. Gautier,

Maxime G. Zermatten

et al.

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2024

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Cited by 2 publications

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Comparison of the Efficacy and Safety of Direct Oral Anticoagulants and Warfarin in Cirrhotic Patients: A Systematic Review and Meta-Analysis

Cheng,

Hua,

Xiong

2024

Clin Appl Thromb Hemost

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Objective Currently, there is limited evidence regarding the use of direct oral anticoagulants (DOACs) for patients with liver cirrhosis (LC). We performed a meta-analysis to compare the efficacy and safety of DOACs versus warfarin in this population. Methods We searched PubMed, Cochrane Library, Web of Science, Embase and Scopus databases from inception to August 2024. Clinical studies comparing the use of DOACs with warfarin in cirrhotic patients were included. Hazard ratios (HRs) with 95% CIs were estimated by either fixed or random effects models. Primary efficacy outcomes were ischemic stroke/thromboembolism (IS/TE) and all-cause death, the primary safety outcomes were the bleeding risks. Results Sixteen studies were included (16 829 individuals). DOACs had similar benefits in preventing IS/TE (HR = 0.87, 95% CI: 0.69-1.10), but DOACs were significantly associated with reduced risk of all-cause death (HR = 0.87, 95% CI: 0.79-0.97). On the other hand, we observed significantly reduced risks of any bleeding (HR = 0.60; 95%CI: 0.37-0.95), major bleeding (HR = 0.72; 95%CI: 0.63-0.82), intracranial hemorrhage (ICH) (HR = 0.47; 95%CI: 0.30-0.73), and gastrointestinal bleeding (GIB) (HR = 0.72, 95% CI: 0.60-0.87) in patients receiving DOACs. Results were consistent in cirrhotic patients with AF. Furthermore, DOACs reduced the incidence of major bleeding (HR = 0.65, 95%CI: 0.55-0.78) and ICH (HR = 0.17, 95%CI: 0.04-0.76) in patients with moderate to severe cirrhosis. Conclusion Our study demonstrates that DOACs, compared with warfarin, exerted comparable efficacy and better safety and may represent a safer alternative to warfarin in cirrhotic patients.

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Comparison of the Efficacy and Safety of Direct Oral Anticoagulants and Warfarin in Cirrhotic Patients: A Systematic Review and Meta-Analysis

Cheng,

Hua,

Xiong

2024

Clin Appl Thromb Hemost

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Endothelial Dysfunction and Liver Cirrhosis: Unraveling of a Complex Relationship

Nesci,

Ruggieri,

Manilla

et al. 2024

IJMS

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Endothelial dysfunction (ED) is the in the background of multiple metabolic diseases and a key process in liver disease progression and cirrhosis decompensation. ED affects liver sinusoidal endothelial cells (LSECs) in response to different damaging agents, causing their progressive dedifferentiation, unavoidably associated with an increase in intrahepatic resistance that leads to portal hypertension and hyperdynamic circulation with increased cardiac output and low peripheral artery resistance. These changes are driven by a continuous interplay between different hepatic cell types, invariably leading to increased reactive oxygen species (ROS) formation, increased release of pro-inflammatory cytokines and chemokines, and reduced nitric oxide (NO) bioavailability, with a subsequent loss of proper vascular tone regulation and fibrosis development. ED evaluation is often accomplished by serum markers and the flow-mediated dilation (FMD) measurement of the brachial artery to assess its NO-dependent response to shear stress, which usually decreases in ED. In the context of liver cirrhosis, the ED assessment could help understand the complex hemodynamic changes occurring in the early and late stages of the disease. However, the instauration of a hyperdynamic state and the different NO bioavailability in intrahepatic and systemic circulation—often defined as the NO paradox—must be considered confounding factors during FMD analysis. The primary purpose of this review is to describe the main features of ED and highlight the key findings of the dynamic and intriguing relationship between ED and liver disease. We will also focus on the significance of FMD evaluation in this setting, pointing out its key role as a therapeutic target in the never-ending battle against liver cirrhosis progression.

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Direct oral anticoagulants in cirrhosis: Rationale and current evidence

Cited by 2 publications

References 97 publications

Comparison of the Efficacy and Safety of Direct Oral Anticoagulants and Warfarin in Cirrhotic Patients: A Systematic Review and Meta-Analysis

Comparison of the Efficacy and Safety of Direct Oral Anticoagulants and Warfarin in Cirrhotic Patients: A Systematic Review and Meta-Analysis

Endothelial Dysfunction and Liver Cirrhosis: Unraveling of a Complex Relationship

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