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A network meta-analysis of direct oral anticoagulants for portal vein thrombosis in cirrhosis

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Abstract

Background

Current guidelines have limited consensus on the approach to portal venous thrombosis (PVT) in cirrhotic patients. While there is rising interest in direct oral anticoagulants (DOACs) use for PVT, current evidence is limited by small sample size and lack of comparisons to traditional anticoagulants. Thus, a network meta-analysis was conducted to compare the use of DOACs with traditional anticoagulants.

Methods

Medline and Embase were searched for articles about anticoagulation use in cirrhotic patients with nontumorous PVT for articles on DOACs, warfarin, low-molecular weight heparin (LMWH) or antithrombin III. A network analysis was conducted using risk ratios (RR) with surface under the cumulative ranking curve (SUCRA). A single-arm meta-analysis was used to summarize the outcomes of DOAC treatment.

Results

A total of 10 articles were included in the study. 79.5% (CI 38.8–95.9) of DOACs patients achieved complete or partial recanalization and 9.80% (CI 4.50–20.0) experienced a bleeding event. DOACs were superior to LMWH (RR 2.299, CI 1.037–5.093, p = 0.040), warfarin (RR 1.762, CI 1.017–3.053, p = 0.043) and no treatment (RR 3.489, CI 1.394–8.733, p = 0.008) in complete recanalization. For partial recanalization, while DOACs were not superior to any treatment, they had the highest probability in achieving partial recanalization in SUCRA analysis. Bleeding risk and mortality were similar compared to other treatments.

Conclusion

The network analysis supports the use of DOACs in cirrhotic patients, with significant rates of complete recanalization compared to other treatments without increasing bleeding risk. DOACs can potentially be considered for nontumorous PVT in cirrhosis.

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Data availability

All data are available from Medline and Embase databases.

Abbreviations

DOACs:

Direct oral anticoagulants

PVT:

Portal vein thrombosis

LMWH:

Low-molecular weight heparin

CRNMB:

Clinically relevant non-major bleeding

RR:

Risk Ratio

SUCRA:

Surface under the cumulative ranking curve

JBI:

Joanna Briggs Institute

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Funding

This study receives no external funding. There are no funding interests to declare.

Author information

Author notes

  1. ChengHan Ng and DarrenJunHao Tan contributed equally.

Authors and Affiliations

  1. Yong Loo Lin School of Medicine, National University of Singapore, 10 Medical Dr, Singapore, 117597, Singapore

    Cheng Han Ng, Darren Jun Hao Tan, Kameswara Rishi Yeshayahu Nistala, Nicholas Syn, Jieling Xiao, Eunice Xiang Xuan Tan, Daniel Q. Huang, Yock Young Dan & Mark D. Muthiah

  2. Biostatistics and Modelling Domain, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, Singapore

    Nicholas Syn

  3. Department of Pharmacy, National University Hospital, Singapore, Singapore

    Felicia Zuying Woo

  4. National University Centre for Organ Transplantation, National University Health System, Singapore, Singapore

    Eunice Xiang Xuan Tan, Felicia Zuying Woo, Daniel Q. Huang, Yock Young Dan & Mark D. Muthiah

  5. Division of Cardiology, Department of Medicine, National University Hospital, Singapore, Singapore

    Nicholas W. S. Chew

  6. Division of Gastroenterology and Hepatology, Department of Medicine, National University Hospital, Tower Block Level 10, 1E Kent Ridge Road, Singapore, 119228, Singapore

    Eunice Xiang Xuan Tan, Daniel Q. Huang, Yock Young Dan & Mark D. Muthiah

  7. Department of Internal Medicine, Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University, Richmond, Virginia, USA

    Arun J. Sanyal

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  1. Cheng Han Ng
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Contributions

CHN and DJHT should be considered joint first author. MDM and CHN act as the joint submission guarantor. All authors approve the final version of the manuscript, including the authorship list and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Conceptualization and Design: CHN, FZW, NC, DQH, YYD, AJS, MDM. Acquisition of Data: CHN, DJHT, KRYN, JX. Analysis and Interpretation of Data: CHN, NS. Writing—original draft: CHN, DJHT, KRYN, NS, JX, FZW, NC. Writing—review and editing: DQH, YYD, AJS, MDM.

Corresponding authors

Correspondence to Cheng Han Ng or Mark D. Muthiah.

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Conflict of interest

Arun J. Sanyal: Dr Sanyal is President of Sanyal Biotechnology and has stock options in Genfit, Akarna, Tiziana, Indalo, Durect and Galmed. He has served as a consultant to Astra Zeneca, Nitto Denko, Enyo, Ardelyx, Conatus, Nimbus, Amarin, Salix, Tobira, Takeda, Jannsen, Gilead, Terns, Birdrock, Merck, Valeant, Boehringer‐Ingelheim, Lilly, Hemoshear, Zafgen, Novartis, Novo Nordisk, Pfizer, Exhalenz and Genfit. He has been an unpaid consultant to Intercept, Echosens, Immuron, Galectin, Fractyl, Syntlogic, Affimune, Chemomab, Zydus, Nordic Bioscience, Albireo, Prosciento, Surrozen and Bristol Myers Squibb. His institution has received grant support from Gilead, Salix, Tobira, Bristol Myers, Shire, Intercept, Merck, Astra Zeneca, Malinckrodt, Cumberland and Novartis. He receives royalties from Elsevier and UptoDate. Remaining authors have no conflicts of interest to declare.

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Ng, C.H., Tan, D.J.H., Nistala, K.R.Y. et al. A network meta-analysis of direct oral anticoagulants for portal vein thrombosis in cirrhosis. Hepatol Int 15, 1196–1206 (2021). https://doi.org/10.1007/s12072-021-10247-x

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