DOACs in Budd-Chiari syndrome: A real-world comparison from the TriNetX Global Collaborative Network

DOACs in Budd-Chiari syndrome: A real-world comparison from the TriNetX Global Collaborative Network | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article DOACs in Budd-Chiari syndrome: A real-world comparison from the TriNetX Global Collaborative Network Nisar Amin, Muhammed Ceesay, Mark Ayoub, Ebubekir Daglilar, Amir Kamran This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6481491/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 11 You are reading this latest preprint version Abstract Background Anticoagulation is the cornerstone treatment for all types of Budd-Chiari Syndrome (BCS), often requiring lifelong therapy. While heparin and warfarin have traditionally been the primary treatments, Warfarin carries a significant bleeding risk, highlighting the need for more tailored strategies. Recently, direct oral anticoagulants (DOACs) have emerged as a potential alternative. Though off-label for BCS, there is limited existing literature on their safety and efficacy, emphasizing the need for further research. Methods This study used the TriNetX database, a multicenter platform encompassing over 270 million patients from 120 healthcare organizations globally. The dataset included adults (≥ 18 years) diagnosed with BCS who received anticoagulation therapy with warfarin or DOACs between 2006 and 2024. Exclusion criteria included other systemic thrombosis, end-stage renal disease (ESRD), pregnancy, platelet counts < 50×10³/µL, or malignant neoplasms of the liver or biliary system. Two cohorts were created: patients treated with warfarin versus those treated with DOACs within two weeks of BCS diagnosis. Propensity score matching (PSM) adjusted for confounders such as sex, ethnicity, antiplatelet use, smoking, and chronic diseases, creating well-matched groups. TriNetX's statistical platform was utilized to compare one-year and two-years outcomes, including major bleeding, transjugular intrahepatic portosystemic shunt (TIPS) procedures performed, spontaneous bacterial peritonitis (SBP), and mortality. Results A total of 15,245 patients diagnosed with BCS were identified, of whom 2,566 were treated with warfarin and 3,066 with any DOACs. PSM was used to create two 1:1 matched cohorts of 381 patients each. At the one-year follow-up, the rate of major bleeding in patients treated with warfarin compared to those treated with DOACs was 9.7% vs. 7.6% (P = 0.30). The rates of TIPS procedures (3.7% vs. 3.7%, P = 1) and SBP (3.4% vs. 2.6%, P = 0.53) were similar between the groups. Similarly, overall mortality rates were higher in the warfarin group but not statistically significant (11.0% vs. 8.4%, P = 0.22). At the two-year follow-up, major bleeding rates remained higher in the warfarin group, although the difference was not statistically significant (11.7% vs. 9.0%, P = 0.23). The rates of TIPS procedures (3.4% vs. 4.8%, P = 0.36) and SBP (3.4% vs. 2.7%, P = 0.52) continued to show no significant differences between the groups. Conclusions This study found that DOACs were comparable in safety in terms of risk of bleeding and effectiveness in terms of frequency of need for TIP and frequency of SBP to warfarin for BCS patients. While warfarin-treated patients had slightly higher rates of major bleeding and mortality at one- and two-year follow-ups, the differences were not statistically significant. Rates of TIPS procedures and SBP were similar between groups. These findings suggest DOACs as a potential alternative to warfarin, offering patients the advantage of a reduced need for frequent laboratory monitoring required with warfarin and simplified medication management These findings support the need for longer term and broader studies to evaluate the safety and efficiency of DOACs in this unique population. Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Budd-Chiari Syndrome (BCS) is a rare but life-threatening disorder that can lead to severe liver dysfunction, portal hypertension, and hepatic failure if not promptly diagnosed and treated. Due to its rarity, determining the population-based incidence of Budd-Chiari Syndrome remains challenging. An epidemiological study from South Korea reported an average age- and sex-adjusted incidence of 0.87 cases per million per year [ 1 ]. Meanwhile, a hospital-based study in India found that BCS accounted for 4% of portal hypertension cases [ 2 ]. BCS is characterized by obstruction of the hepatic veins, excluding sinusoidal obstruction syndrome and cardiac causes [ 3 ]. It is classified as either primary or secondary based on the underlying pathology. Studies have shown that the hepatic veins are the most common sites of obstruction [ 4 ], however, research conducted in China has identified combined obstruction of the inferior vena cava and hepatic veins as the most prevalent form of Budd-Chiari Syndrome [ 5 – 7 ]. Primary BCS typically arises from partial or complete thrombosis of the hepatic vein, often linked to prothrombotic states. European studies have identified an underlying prothrombotic state in 88% of patients with Budd-Chiari Syndrome [ 8 ], while recent research from India has reported similar findings, with up to 85% of BCS patients exhibiting a prothrombotic condition [ 9 – 12 ]. In contrast, secondary BCS, which comprises less than 1% of the total cases [ 13 ], results from external compression caused by tumors or other factors [ 14 ]. The condition is more prevalent in Asian populations but remains rare in Western countries, with an incidence of approximately 1 per 2.5 million person-years [ 15 ]. Treatment involves addressing the underlying disease, anticoagulation therapy, vein recanalization, transjugular intrahepatic portosystemic shunt (TIPS) procedures, and liver transplantation [ 16 ]. Anticoagulation is the cornerstone treatment for all types of BCS, often requiring lifelong therapy. Heparin and vitamin K antagonists (VKAs) have traditionally been used, but VKAs are associated with a high risk of bleeding complications, with rates as high as 17–50%, underscoring the need for tailored therapeutic approaches[ 17 ]. Direct oral anticoagulants (DOACs) have emerged as a potential treatment option for BCS. While their use in BCS remains off-label, recent studies have provided some insights into their efficacy and safety. Direct oral anticoagulants (DOACs), such as rivaroxaban, dabigatran, and apixaban, do not require routine monitoring. A study by the VALDIG consortium, in which patients with Budd-Chiari syndrome (BCS) made up 14% of the study population, found that DOACs demonstrated similar safety and efficacy compared to vitamin K antagonists [ 18 ]. A retrospective Australian cohort study by Semler et al., involving 47 BCS patients, found DOACs to be effective and safe for long-term anticoagulation, reporting a complete response in 63.6% of patients and a 5-year transplant-free survival rate of 91.6% [ 19 ]. Another study comparing dabigatran to VKAs in BCS patients’ post-endovascular intervention showed similar stent patency rates and bleeding complications between the groups [ 20 ]. Despite these findings, the American College of Gastroenterology (ACG) guidelines currently do not recommend DOACs as first-line treatment for BCS due to the lack of large prospective studies. Instead, the ACG recommends warfarin or low-molecular-weight heparin (LMWH) as the preferred anticoagulation strategies for BCS management [ 21 ]. However, unfractionated heparin is generally not recommended due to the risk of heparin-induced thrombocytopenia and required route of subcutaneous injection administration and should be reserved for special cases such as severe renal impairment or pending invasive procedures [ 22 ]. A key takeaway from Baveno VII is the increasing role of anticoagulation in managing vascular liver diseases, with growing recognition of direct oral anticoagulants (DOACs) as safer and effective alternatives to vitamin K antagonists (VKAs) in selected patients. Given that BCS requires lifelong anticoagulation, the safety profile of DOACs, particularly regarding bleeding risk, thrombotic recurrence, and impact on hepatic function, aligns with the Baveno VII focus on personalized management. Integrating the insights from this consensus into BCS treatment paradigms could provide a stronger foundation for evaluating DOACs as a first-line therapy, reinforcing their role in maintaining hepatic perfusion while mitigating complications associated with traditional anticoagulation. While DOACs offer potential advantages over VKAs, including fewer drug interactions and limiting the need for routine monitoring, their role in BCS remains unclear due to the paucity of large-scale studies evaluating their safety and efficacy. Given the increasing use of DOACs in clinical practice and the lack of robust comparative data, this study seeks to evaluate their safety in BCS using a large, real-world cohort from the TriNetX database. By leveraging a multicenter dataset, this analysis aims to provide broader insights into the safety and potential benefits of DOACs compared to traditional anticoagulation in BCS management. MATERIALS AND METHODS This retrospective cohort study analyzed longitudinal medical data from the Global Collaborative Network, a TriNetX Research Network comprising 120 healthcare organizations across 30 countries, with de-identified records from over 270 million patients. The database includes patient demographics, diagnoses, procedures, medications, laboratory tests, and healthcare utilization, ensuring privacy while enabling robust analysis [ 23 ]. The database was queried to identify adults (≥ 18 years) diagnosed with Budd-Chiari Syndrome (BCS) between 2006 and 2024 who received treatment with either warfarin or any of the DOACs. Patients were included if they had a new diagnosis of BCS and were subsequently started on warfarin or a DOAC (apixaban, rivaroxaban, dabigatran, or edoxaban). Patients were excluded if they had a diagnosis of deep venous thrombosis or pulmonary embolism (DVT/PE) or other systemic thrombosis requiring anticoagulation, platelet count 25 mIU/mL, end stage renal disease (ESRD), or hepatobiliary cancer. The ICD-10 and CPT codes used for patient identification, as well as the inclusion and exclusion criteria, are detailed in Supplement-1. Two cohorts were created. Cohort one included patients meeting the inclusion criteria who were started on warfarin within two weeks of BCS diagnosis. Cohort two included patients meeting the inclusion criteria who were started on any of the DOACs within two weeks of BCS diagnosis. To further eliminate confounding factors and remove patients who switched between anticoagulation classes, individuals with any prescription of an alternate anticoagulation class during the follow-up period were excluded. Propensity score matching (1:1 nearest neighbor) was performed to balance baseline characteristics and comorbidities. Variables included age, race, ethnicity, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, heart failure, tobacco use, alcohol use, and prescribed antiplatelets (aspirin or clopidogrel ). Statistical significance was set at P < 0.05 with 95% confidence intervals. Kaplan-Meier survival analysis, as implemented within the internal TriNetX analytics platform, was used to estimate time-to-event outcomes and survival probabilities. The primary outcome was major bleeding, operationally defined as any esophageal, non-traumatic intracranial, or gastrointestinal (GI) bleeding event. The secondary outcomes included spontaneous bacterial peritonitis (SBP), transjugular intrahepatic portosystemic shunt (TIPS) procedure, and mortality within one-year and two-year. The study flow diagram is presented in Fig. 1 . RESULTS From a total of 15,245 patients with Budd-Chiari Syndrome in the TriNetX database, 6.6% (n = 1,013) were included in this analysis after applying the exclusion criteria, of which 54% (n = 551) received anticoagulation with any of the DOACs, and 46% (n = 462) received anticoagulation with warfarin. Two well-matched cohorts (381 patients each) were created using 1:1 Propensity Score Matching (PSM). Before matching, patients in the DOACs group were older (50.6 ± 17.8 vs. 54.1 ± 17.8, p < 0.002) and had a lower rate of hypertensive disease (34% vs. 44%, p = 0.004). Both groups had similar rates of chronic obstructive pulmonary disease (6% vs. 7%), coronary artery disease (8% vs. 12%), heart failure (10% vs. 10%), diabetes mellitus (20% vs. 21%), tobacco use (2% vs. 5%), alcohol use (5% vs. 8%), aspirin use (22% vs. 27%), and clopidogrel use (5% vs. 3%), with no statistically significant differences. PSM was conducted using baseline characteristics, including demographics, comorbidities, smoking, alcohol use, aspirin use, and clopidogrel use. Post-PSM, no significant differences were observed between the warfarin and DOAC cohorts. A detailed comparison is provided in Table 1 . Table 1 Baseline Characteristics of Study Cohorts Before and After Propensity Matching Before Propensity Score Matching After Propensity Score Matching Warfarin (n = 462) DOACs (n = 551) p-value Warfarin (n = 381) DOACs (n = 381) p-value Demographics Age at Index, Mean years ± SD 50.6 ± 17.8 54.1 ± 17.8 0.01 51.6 ± 17.7 50.9 ± 17.4 0.56 Female 231 (56) 306 (55) 0.80 211 (55) 211 (55) 1.00 Male 173 (42) 234 (43) 0.93 164 (43) 165 (43) 0.94 Race White 256 (62) 327 (59) 0.33 238 (63) 234 (61) 0.77 Black or African American 31 (7.6) 64 (12) 0.04 31 (8) 35 (9) 0.61 Unknown 84 (21.5) 106 (19) 0.63 75 (20) 72 (19) 0.78 Comorbidities Heart failure 41 (10) 54 (10) 0.92 37 (10) 34 (9) 0.71 COPD 23 (6) 37 (7) 0.48 23 (6) 21 (6) 0.76 Hypertensive diseases 142 (35) 241 (44) 0.00 138 (36) 140 (37) 0.88 CAD 34 (8) 66 (12) 0.06 32 (8) 38 (10) 0.45 Diabetes mellitus 81 (20) 114 (21) 0.72 76 (20) 70 (18) 0.58 Tobacco use 10 (2) 25 (5) 0.07 10 (3) 10 (3) 1.00 Alcohol abuse 21 (5) 44 (8) 0.08 21 (6) 21 (6) 0.88 Medication Aspirin 90 (22) 149 (27) 0.07 87 (23) 78 (21) 0.43 Clopidogrel 20 (5) 19 (3) 0.27 16 (4) 17 (5) 0.86 COPD: chronic obstructive lung disease. CAD: coronary artery disease. Primary Outcomes The primary outcome of the study was major bleeding, defined as a composite of esophageal bleeding, gastrointestinal (GI) bleeding, or nontraumatic intracranial bleeding at one-year and two-year follow-ups. Two well-matched cohorts of 381 patients each were created using a 1:1 propensity score matching model. Post-matching analysis revealed that patients who received warfarin had a higher overall frequency of major bleeding rate though the difference was not statistically significant at one year (9.7% vs. 7.6%, P = 0.30) and two years (11.7% vs. 9.0%, P = 0.23). Kaplan-Meier curves illustrating the overall bleeding rates at one year follow up presented in Fig. 2 . Subgroup analysis of bleeding at one-year follow-up revealed a higher GI bleeding rate in the warfarin group (9.2% vs. 7.1%, P = 0.30), though this difference was not statistically significant. Similarly, the esophageal bleeding rate (2.6% vs. 2.6%, P = 1.00) and nontraumatic intracranial bleeding rate (2.6% vs. 2.6%, P = 1.00) were identical in both groups. Secondary Outcomes The secondary outcomes of the study included the incidence of TIPS procedure, spontaneous bacterial peritonitis (SBP), and mortality. The rate of TIPS procedure frequency in the warfarin versus DOAC group was 3.7% vs. 3.7%, respectively (P = 1.00) at one year and 3.4% vs. 4.8% (P = 0.36) at two years, showing an increase in the DOACs group at the two-year follow-up but no significant difference between the groups. The incidence of SBP in the warfarin versus group was 3.4% vs. 2.6%, respectively (P = 0.53) at one year and 3.4% vs. 2.7% (P = 0.52) at two years, indicating higher frequency in the warfarin group, though this difference was not statistically significant. Similarly, overall mortality rates were higher in the warfarin group, with 11.0% vs. 8.4% (P = 0.22) at one year and 13.8% vs. 11.4% (P = 0.32) at two years, though these differences did not reach statistical significance. Kaplan-Meier curves illustrating the secondary outcomes at one year follow up presented in Fig. 3 . DISCUSSION This study provides a real-world comparison of key components of safety and efficacy of direct oral anticoagulants (DOACs) versus warfarin in patients with Budd-Chiari Syndrome (BCS), a vascular liver disorder that necessitates lifelong anticoagulation to prevent disease progression and recurrent thrombosis [ 24 – 26 ]. DOACs are increasingly being used in patients with liver disease and are generally considered safe in those with compensated hepatic function [ 27 , 28 ]. Notably, individuals with significant liver disease were excluded from Phase III DOAC trials [ 28 , 29 ], limiting robust data on their safety in this population. However, emerging evidence suggests a heightened bleeding risk in individuals with more advanced liver disease [ 30 ]. Complexity of warfarin management is of concern in patients with hepatic dysfunction possibly warranting a greater frequency of laboratory testing in clinical practice. Prior studies have reported notable bleeding rates among cirrhotic patients receiving DOACs, with Mort et al. [ 31 ] documenting a 21% bleeding incidence in patients with decompensated cirrhosis over a median follow-up of six months. Additionally, de Gottardi et al.[ 18 ] observed an overall bleeding rate of 13.9% in cirrhotic patients using DOACs over a median duration of seven months. Given these concerns, our findings indicating lower, albeit statistically non-significant, major bleeding rates with DOACs compared to warfarin in BCS patients provide valuable insight into their potential role as an alternative anticoagulation strategy. Further studies are warranted to confirm these observations and delineate the safety profile of DOACs in this unique population. Rates of transjugular intrahepatic portosystemic shunt (TIPS) procedures were similar between the DOAC and warfarin groups at both one- and two-year follow-ups. This finding suggests that anticoagulation choice may not significantly influence the need for invasive intervention in BCS. According to a retrospective cohort study conducted at the University of Pennsylvania, 44.7% of BCS patients received TIPS, with 90.5% of these patients also on anticoagulation [ 32 ]. Another study reported that 39.5% of patients underwent TIPS in a large prospective multicenter European study, with a median overall follow-up of 50 months [ 33 ]. Additionally, a study involving 124 BCS patients treated with TIPS across six European centers indicated that TIPS was a common intervention, although the exact percentage of patients on anticoagulation was not specified [ 34 ]. In contrast, our study demonstrated significantly lower rates of TIPS utilization, with only 3.7% of patients in both the warfarin and DOAC cohorts requiring the procedure at one year and 3.4% vs. 4.8% at two years. This discrepancy may reflect differences in patient selection, disease severity, or institutional management strategies. Unlike prior studies that reported higher TIPS rates, our findings suggest that early and effective anticoagulation, regardless of agent choice, may reduce the need for invasive intervention in carefully selected patients. While the slight increased frequency in TIPS procedures in the DOAC group at two years was not statistically significant (P = 0.36), it raises questions about whether longer follow-up might reveal subtle differences in disease progression between anticoagulant groups. Ultimately, our results highlight the importance of individualized management in BCS and suggest that further research is needed to refine criteria for selecting patients who truly benefit from early TIPS placement. Given that TIPS is typically reserved for patients with progressive hepatic congestion and portal hypertension [ 35 ], our results indicate that DOACs do not appear to increase the likelihood of requiring these procedures compared to warfarin. However, further studies evaluating hemodynamic differences between the two anticoagulation strategies would be valuable in confirming these findings. In our study, we found that the incidence of spontaneous bacterial peritonitis (SBP) was comparable between the DOAC and warfarin groups at both one- and two-year follow-ups, with rates of 3.4% vs. 2.6% respectively (P = 0.53) at one year and 3.4% vs. 2.7% (P = 0.52) at two years. Although there was a slightly higher SBP rate in the warfarin group, this difference was not statistically significant, aligning with previous studies suggesting that anticoagulation choice does not substantially impact SBP risk in BCS patients. These findings reinforce the assertion that SBP risk is likely driven more by the severity of liver disease and portal hypertension rather than the anticoagulation strategy itself. Given the complexity of SBP pathophysiology in BCS, future research incorporating liver disease severity scores, such as the Model for End-Stage Liver Disease (MELD) score or the Child-Pugh classification system, may help determine whether specific patient subgroups have differential risks based on anticoagulation type. Although the overall mortality rate was slightly higher in the warfarin group compared to the DOAC group at both one and two years, this difference was not statistically significant. A study by Pavri et al. reported that among 47 BCS patients, 40 (85.1%) were on anticoagulation, with 30 (63.8%) maintained on warfarin. Over a median follow-up of 974 days, 10 patients (21.3%) died, indicating a significant mortality rate in this cohort [ 7 ]. Another study by Sharma et al. found that the 1-year and 5-year survival rates for BCS patients on anticoagulation were 94.2% and 87.5%, respectively, suggesting that long-term survival can be favorable with appropriate management [ 15 ]. The non-significance of mortality outcomes in our study suggests that neither anticoagulant provided a clear survival advantage in the studied cohort. However, given the retrospective nature of our study, potential confounders such as underlying liver dysfunction, thrombotic burden, and adherence to anticoagulation therapy must be considered when interpreting these results. Our findings mirror prior research suggesting that while anticoagulation is essential in BCS management, survival outcomes are likely influenced by a complex interplay of patient-specific factors beyond the choice of anticoagulant. Given that DOACs are increasingly utilized in practice, further research is warranted to determine whether differences in drug metabolism, adherence, or hepatic function influence long-term outcomes in this patient population. Additionally, stratification based on liver disease severity or thrombotic burden may help elucidate whether certain subgroups could benefit more from one anticoagulation strategy over another. Our study has several strengths. By leveraging the TriNetX database, a global research network encompassing diverse healthcare systems across multiple countries, our findings benefit from a broad and representative patient population, enhancing their generalizability. Additionally, our study methodology resulted in a robust sample size despite the rarity of this disorder, allowing for more precise estimates of outcomes and subgroup analyses. To further strengthen the validity of our results, we employed propensity score matching, minimizing the impact of confounding variables and ensuring a more balanced comparison between the DOAC and warfarin groups. This methodological rigor enhances the reliability of our conclusions and underscores the relevance of our findings in real-world clinical practice. On the other hand, the limitations of our study include the potential for residual confounding despite the use of propensity score matching. Second, we lacked data on the specific types and dosages of DOACs used, which may influence safety and efficacy outcomes. Third, the study population was drawn from a large global database, potentially introducing heterogeneity in clinical practices across different healthcare institutions. Lastly, follow-up duration was limited to two years, and longer-term outcomes remain unknown. Future research, particularly prospective studies with randomized designs would be the gold standard to further elucidate the role of DOACs in BCS management, however recognizing the challenge of such research present in rarer conditions such as this are potentially prohibitive Clinical registries that employ a multi-center approach may be a viable alternative to studying patient characteristics, treatment and outcomes over long periods and in real-world settings. In conclusion, our findings suggest that DOACs are a viable alternative to warfarin for BCS patients, demonstrating comparable safety and effectiveness. While the non-significant trend toward lower bleeding and mortality rates with DOACs is promising, additional research is needed to validate these findings. Declarations Ethics approval This study was approved by the CAMC/WVU Charleston Division IRB Review Board under protocol number 24-1159 Human Ethics and Consent to Participate declarations Not applicable. Consent to Publish declaration : Not applicable. Funding The authors received no financial support for the research, authorship, or publication of this article. Author Contribution N.A. conceived the study, designed the methodology, and conducted the data analysis. M.A. contributed to data acquisition, assisted in statistical analysis, and helped interpret the results. M.C. contributed to data interpretation and wrote the initial draft of the manuscript. E.D. and A.K. provided critical revision of the manuscript for important intellectual content and contributed to the clinical contextualization of findings. All authors reviewed and approved the final manuscript. References Ki M, et al. Incidence, prevalence and complications of Budd-Chiari syndrome in South Korea: a nationwide, population-based study. Liver Int. 2016;36(7):1067–73. Goel A, et al. A study of aetiology of portal hypertension in adults (including the elderly) at a tertiary centre in southern India. Indian J Med Res. 2013;137(5):922–7. Darwish Murad S, et al. Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Intern Med. 2009;151(3):167–75. Perello A, et al. TIPS is a useful long-term derivative therapy for patients with Budd-Chiari syndrome uncontrolled by medical therapy. Hepatology. 2002;35(1):132–9. Cheng D, et al. Clinical features and etiology of Budd-Chiari syndrome in Chinese patients: a single-center study. J Gastroenterol Hepatol. 2013;28(6):1061–7. Qi X, et al. Thrombotic risk factors in Chinese Budd-Chiari syndrome patients. An observational study with a systematic review of the literature. Thromb Haemost. 2013;109(5):878–84. Gao X, et al. Risk factors of recurrence among 471 Chinese patients with Budd-Chiari syndrome. Clin Res Hepatol Gastroenterol. 2015;39(5):620–6. Denninger MH, et al. Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. Hepatology. 2000;31(3):587–91. Amarapurkar DN, Punamiya SJ, Patel ND. Changing spectrum of Budd-Chiari syndrome in India with special reference to non-surgical treatment. World J Gastroenterol. 2008;14(2):278–85. Dayal S, et al. Multilineage hemopoietic stem cell defects in Budd Chiari syndrome. J Hepatol. 1997;26(2):293–7. Pati HP, et al. Spectrum of hemostatic derangements, in Budd-Chiari syndrome. Indian J Gastroenterol. 2003;22(2):59–60. Mohanty D, et al. Hereditary thrombophilia as a cause of Budd-Chiari syndrome: a study from Western India. Hepatology. 2001;34(4 Pt 1):666–70. Zhang W et al. Budd-Chiari Syndrome in China: A Systematic Analysis of Epidemiological Features Based on the Chinese Literature Survey. Gastroenterol Res Pract, 2015. 2015: p. 738548. Hitawala AA, Gupta V. Budd-Chiari Syndrome , in StatPearls . Treasure Island (FL); 2025. Coilly A, et al. Budd-Chiari syndrome. Clin Res Hepatol Gastroenterol. 2020;44(4):420–5. Sharma A, et al. An Update on the Management of Budd-Chiari Syndrome. Dig Dis Sci. 2021;66(6):1780–90. Rautou PE, et al. Bleeding in patients with Budd-Chiari syndrome. J Hepatol. 2011;54(1):56–63. De Gottardi A, et al. Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis. Liver Int. 2017;37(5):694–9. Semmler G, et al. Outcome of Budd-Chiari Syndrome Patients Treated With Direct Oral Anticoagulants: An Austrian Multicenter Study. Clin Gastroenterol Hepatol. 2023;21(4):978–87. e2. Sharma S, et al. Dabigatran as an oral anticoagulant in patients with Budd-Chiari syndrome post-percutaneous endovascular intervention. J Gastroenterol Hepatol. 2020;35(4):654–62. Simonetto DA, et al. ACG Clinical Guideline: Disorders of the Hepatic and Mesenteric Circulation. Am J Gastroenterol. 2020;115(1):18–40. de Franchis R, et al. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959–74. Amin N et al. Outcomes of Outpatient Elective Esophageal Varices Band Ligation in Cirrhosis Patients with Significant Thrombocytopenia. Diseases, 2025. 13(2). European Association for the Study of the Liver. Electronic address, e.e.e., EASL Clinical Practice Guidelines: Vascular diseases of the liver . J Hepatol. 2016;64(1):179–202. Shukla A, et al. Budd-Chiari syndrome: consensus guidance of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int. 2021;15(3):531–67. Northup PG, et al. Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;73(1):366–413. Di Nisio M, et al. Anticoagulant therapy for splanchnic vein thrombosis: ISTH SSC Subcommittee Control of Anticoagulation. J Thromb Haemost. 2020;18(7):1562–8. Agnelli G, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699–708. Investigators E, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499–510. Semmler G, et al. Safety of direct oral anticoagulants in patients with advanced liver disease. Liver Int. 2021;41(9):2159–70. Mort JF, et al. Rates of Bleeding and Discontinuation of Direct Oral Anticoagulants in Patients With Decompensated Cirrhosis. Clin Gastroenterol Hepatol. 2021;19(7):1436–42. Pavri TM, et al. Budd-Chiari syndrome: a single-center experience. World J Gastroenterol. 2014;20(43):16236–44. Seijo S, et al. Good long-term outcome of Budd-Chiari syndrome with a step-wise management. Hepatology. 2013;57(5):1962–8. Garcia-Pagan JC, et al. TIPS for Budd-Chiari syndrome: long-term results and prognostics factors in 124 patients. Gastroenterology. 2008;135(3):808–15. Sharma A, et al. Anticoagulating Budd-Chiari syndrome patients presenting with variceal bleed: A retrospective study. J Gastroenterol Hepatol. 2020;35(8):1397–403. Additional Declarations No competing interests reported. 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Amin","email":"data:image/png;base64,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","orcid":"","institution":"Charleston Area Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Nisar","middleName":"","lastName":"Amin","suffix":""},{"id":516243766,"identity":"ad35e1ec-ba74-49c3-b192-ea4173bc822f","order_by":1,"name":"Muhammed Ceesay","email":"","orcid":"","institution":"Charleston Area Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Muhammed","middleName":"","lastName":"Ceesay","suffix":""},{"id":516243767,"identity":"fd8462f8-92d3-4187-b6fc-c59d187aab59","order_by":2,"name":"Mark Ayoub","email":"","orcid":"","institution":"Charleston Area Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Mark","middleName":"","lastName":"Ayoub","suffix":""},{"id":516243768,"identity":"00ae13e0-141a-401d-889e-0b98ce713b8a","order_by":3,"name":"Ebubekir Daglilar","email":"","orcid":"","institution":"Charleston Area Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Ebubekir","middleName":"","lastName":"Daglilar","suffix":""},{"id":516243769,"identity":"25482c5e-dd75-4ade-81e2-0c0816750944","order_by":4,"name":"Amir Kamran","email":"","orcid":"","institution":"Charleston Area Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Amir","middleName":"","lastName":"Kamran","suffix":""}],"badges":[],"createdAt":"2025-04-18 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09:33:12","extension":"xml","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":81718,"visible":true,"origin":"","legend":"","description":"","filename":"b9f7effc880f4da68d8e6fac42428f0f1structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-6481491/v1/6f34bd839cfa8c9e7999f883.xml"},{"id":91835663,"identity":"a7d1fd08-95c7-4af4-a304-e6e7731f13e2","added_by":"auto","created_at":"2025-09-22 09:33:12","extension":"html","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":94164,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-6481491/v1/534312733250e8896c85cfd1.html"},{"id":91838721,"identity":"17736d18-d70d-44e1-9738-6a0de24cf324","added_by":"auto","created_at":"2025-09-22 09:49:12","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":253230,"visible":true,"origin":"","legend":"\u003cp\u003eStudy flow diagram\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6481491/v1/c571df7109332cb257208136.jpeg"},{"id":91835658,"identity":"d31d7d8d-3d4c-4147-b900-e978780c4d42","added_by":"auto","created_at":"2025-09-22 09:33:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":203297,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier estimates within one year of treatment with anticoagulation therapy. Bleeding events occurred in 29 of 381 patients who received direct oral anticoagulants (DOACs) and in 37 of 381 patients who received warfarin (Coumadin).\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6481491/v1/d6c8dde78c2bd974d6cf37b5.png"},{"id":91837662,"identity":"65439dd2-bc1d-4b67-b231-365f53e48a4f","added_by":"auto","created_at":"2025-09-22 09:41:12","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":239479,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan–Meier estimates within one year of treatment with anticoagulation therapy. (A) Transjugular intrahepatic portosystemic shunt (TIPS) placement occurred in 14 of 381 patients who received direct oral anticoagulants (DOACs) and in 14 of 381 patients who received warfarin (Coumadin). (B) Spontaneous bacterial peritonitis (SBP) was reported in 10 of 381 patients in the DOAC group and in 13 of 381 patients in the warfarin group. (C) Death occurred in 32 of 381 patients who received DOACs and in 42 of 381 patients who received warfarin.\u003c/p\u003e","description":"","filename":"floatimage311.png","url":"https://assets-eu.researchsquare.com/files/rs-6481491/v1/6227e7234e26c5984cbb698c.png"},{"id":91838722,"identity":"5f7bcbac-91a9-48b1-a77a-5de53c71f568","added_by":"auto","created_at":"2025-09-22 09:49:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1194804,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6481491/v1/da42c47a-e67e-46b2-9e97-4671db19ac69.pdf"},{"id":91835661,"identity":"84472516-5345-44d6-854c-84aff3300e79","added_by":"auto","created_at":"2025-09-22 09:33:12","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":38045,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement1ICD10CodesBCSStudy.docx","url":"https://assets-eu.researchsquare.com/files/rs-6481491/v1/84058ce312d5eb3ae211f847.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"DOACs in Budd-Chiari syndrome: A real-world comparison from the TriNetX Global Collaborative Network","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eBudd-Chiari Syndrome (BCS) is a rare but life-threatening disorder that can lead to severe liver dysfunction, portal hypertension, and hepatic failure if not promptly diagnosed and treated. Due to its rarity, determining the population-based incidence of Budd-Chiari Syndrome remains challenging. An epidemiological study from South Korea reported an average age- and sex-adjusted incidence of 0.87 cases per million per year [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Meanwhile, a hospital-based study in India found that BCS accounted for 4% of portal hypertension cases [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. BCS is characterized by obstruction of the hepatic veins, excluding sinusoidal obstruction syndrome and cardiac causes [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It is classified as either primary or secondary based on the underlying pathology. Studies have shown that the hepatic veins are the most common sites of obstruction [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], however, research conducted in China has identified combined obstruction of the inferior vena cava and hepatic veins as the most prevalent form of Budd-Chiari Syndrome [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Primary BCS typically arises from partial or complete thrombosis of the hepatic vein, often linked to prothrombotic states. European studies have identified an underlying prothrombotic state in 88% of patients with Budd-Chiari Syndrome [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], while recent research from India has reported similar findings, with up to 85% of BCS patients exhibiting a prothrombotic condition [\u003cspan additionalcitationids=\"CR10 CR11\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In contrast, secondary BCS, which comprises less than 1% of the total cases [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e], results from external compression caused by tumors or other factors [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The condition is more prevalent in Asian populations but remains rare in Western countries, with an incidence of approximately 1 per 2.5\u0026nbsp;million person-years [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Treatment involves addressing the underlying disease, anticoagulation therapy, vein recanalization, transjugular intrahepatic portosystemic shunt (TIPS) procedures, and liver transplantation [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eAnticoagulation is the cornerstone treatment for all types of BCS, often requiring lifelong therapy. Heparin and vitamin K antagonists (VKAs) have traditionally been used, but VKAs are associated with a high risk of bleeding complications, with rates as high as 17\u0026ndash;50%, underscoring the need for tailored therapeutic approaches[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Direct oral anticoagulants (DOACs) have emerged as a potential treatment option for BCS. While their use in BCS remains off-label, recent studies have provided some insights into their efficacy and safety. Direct oral anticoagulants (DOACs), such as rivaroxaban, dabigatran, and apixaban, do not require routine monitoring. A study by the VALDIG consortium, in which patients with Budd-Chiari syndrome (BCS) made up 14% of the study population, found that DOACs demonstrated similar safety and efficacy compared to vitamin K antagonists [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A retrospective Australian cohort study by Semler et al., involving 47 BCS patients, found DOACs to be effective and safe for long-term anticoagulation, reporting a complete response in 63.6% of patients and a 5-year transplant-free survival rate of 91.6% [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Another study comparing dabigatran to VKAs in BCS patients\u0026rsquo; post-endovascular intervention showed similar stent patency rates and bleeding complications between the groups [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e Despite these findings, the American College of Gastroenterology (ACG) guidelines currently do not recommend DOACs as first-line treatment for BCS due to the lack of large prospective studies. Instead, the ACG recommends warfarin or low-molecular-weight heparin (LMWH) as the preferred anticoagulation strategies for BCS management [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, unfractionated heparin is generally not recommended due to the risk of heparin-induced thrombocytopenia and required route of subcutaneous injection administration and should be reserved for special cases such as severe renal impairment or pending invasive procedures [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. A key takeaway from Baveno VII is the increasing role of anticoagulation in managing vascular liver diseases, with growing recognition of direct oral anticoagulants (DOACs) as safer and effective alternatives to vitamin K antagonists (VKAs) in selected patients. Given that BCS requires lifelong anticoagulation, the safety profile of DOACs, particularly regarding bleeding risk, thrombotic recurrence, and impact on hepatic function, aligns with the Baveno VII focus on personalized management. Integrating the insights from this consensus into BCS treatment paradigms could provide a stronger foundation for evaluating DOACs as a first-line therapy, reinforcing their role in maintaining hepatic perfusion while mitigating complications associated with traditional anticoagulation. While DOACs offer potential advantages over VKAs, including fewer drug interactions and limiting the need for routine monitoring, their role in BCS remains unclear due to the paucity of large-scale studies evaluating their safety and efficacy.\u003c/p\u003e\u003cp\u003eGiven the increasing use of DOACs in clinical practice and the lack of robust comparative data, this study seeks to evaluate their safety in BCS using a large, real-world cohort from the TriNetX database. By leveraging a multicenter dataset, this analysis aims to provide broader insights into the safety and potential benefits of DOACs compared to traditional anticoagulation in BCS management.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cp\u003eThis retrospective cohort study analyzed longitudinal medical data from the Global Collaborative Network, a TriNetX Research Network comprising 120 healthcare organizations across 30 countries, with de-identified records from over 270\u0026nbsp;million patients. The database includes patient demographics, diagnoses, procedures, medications, laboratory tests, and healthcare utilization, ensuring privacy while enabling robust analysis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe database was queried to identify adults (\u0026ge;\u0026thinsp;18 years) diagnosed with Budd-Chiari Syndrome (BCS) between 2006 and 2024 who received treatment with either warfarin or any of the DOACs. Patients were included if they had a new diagnosis of BCS and were subsequently started on warfarin or a DOAC (apixaban, rivaroxaban, dabigatran, or edoxaban).\u003c/p\u003e\u003cp\u003ePatients were excluded if they had a diagnosis of deep venous thrombosis or pulmonary embolism (DVT/PE) or other systemic thrombosis requiring anticoagulation, platelet count\u0026thinsp;\u0026lt;\u0026thinsp;50,000/\u0026micro;L, beta-human chorionic gonadotropin (β-hCG)\u0026thinsp;\u0026gt;\u0026thinsp;25 mIU/mL, end stage renal disease (ESRD), or hepatobiliary cancer. The ICD-10 and CPT codes used for patient identification, as well as the inclusion and exclusion criteria, are detailed in Supplement-1.\u003c/p\u003e\u003cp\u003eTwo cohorts were created. Cohort one included patients meeting the inclusion criteria who were started on warfarin within two weeks of BCS diagnosis. Cohort two included patients meeting the inclusion criteria who were started on any of the DOACs within two weeks of BCS diagnosis.\u003c/p\u003e\u003cp\u003eTo further eliminate confounding factors and remove patients who switched between anticoagulation classes, individuals with any prescription of an alternate anticoagulation class during the follow-up period were excluded.\u003c/p\u003e\u003cp\u003ePropensity score matching (1:1 nearest neighbor) was performed to balance baseline characteristics and comorbidities. Variables included age, race, ethnicity, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, heart failure, tobacco use, alcohol use, and prescribed antiplatelets (aspirin or clopidogrel ). Statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 with 95% confidence intervals. Kaplan-Meier survival analysis, as implemented within the internal TriNetX analytics platform, was used to estimate time-to-event outcomes and survival probabilities. The primary outcome was major bleeding, operationally defined as any esophageal, non-traumatic intracranial, or gastrointestinal (GI) bleeding event. The secondary outcomes included spontaneous bacterial peritonitis (SBP), transjugular intrahepatic portosystemic shunt (TIPS) procedure, and mortality within one-year and two-year. The study flow diagram is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eFrom a total of 15,245 patients with Budd-Chiari Syndrome in the TriNetX database, 6.6% (n\u0026thinsp;=\u0026thinsp;1,013) were included in this analysis after applying the exclusion criteria, of which 54% (n\u0026thinsp;=\u0026thinsp;551) received anticoagulation with any of the DOACs, and 46% (n\u0026thinsp;=\u0026thinsp;462) received anticoagulation with warfarin. Two well-matched cohorts (381 patients each) were created using 1:1 Propensity Score Matching (PSM).\u003c/p\u003e\u003cp\u003eBefore matching, patients in the DOACs group were older (50.6\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 vs. 54.1\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8, p\u0026thinsp;\u0026lt;\u0026thinsp;0.002) and had a lower rate of hypertensive disease (34% vs. 44%, p\u0026thinsp;=\u0026thinsp;0.004). Both groups had similar rates of chronic obstructive pulmonary disease (6% vs. 7%), coronary artery disease (8% vs. 12%), heart failure (10% vs. 10%), diabetes mellitus (20% vs. 21%), tobacco use (2% vs. 5%), alcohol use (5% vs. 8%), aspirin use (22% vs. 27%), and clopidogrel use (5% vs. 3%), with no statistically significant differences.\u003c/p\u003e\u003cp\u003ePSM was conducted using baseline characteristics, including demographics, comorbidities, smoking, alcohol use, aspirin use, and clopidogrel use. Post-PSM, no significant differences were observed between the warfarin and DOAC cohorts. A detailed comparison is provided in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics of Study Cohorts Before and After Propensity Matching\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eBefore Propensity Score Matching\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eAfter Propensity Score Matching\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eWarfarin\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;462)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDOACs\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;551)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eWarfarin\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;381)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDOACs\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;381)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eDemographics\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge at Index, Mean years\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50.6\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54.1\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e51.6\u0026thinsp;\u0026plusmn;\u0026thinsp;17.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e50.9\u0026thinsp;\u0026plusmn;\u0026thinsp;17.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.56\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e231 (56)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e306 (55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e211 (55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e211 (55)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e173 (42)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e234 (43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e164 (43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e165 (43)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.94\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eRace\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e256 (62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e327 (59)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e238 (63)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e234 (61)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.77\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlack or African American\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31 (7.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64 (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e31 (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.61\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e84 (21.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e106 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e75 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e72 (19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.78\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eComorbidities\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHeart failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.92\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e34 (9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.71\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCOPD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e21 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.76\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertensive diseases\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e142 (35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e241 (44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e138 (36)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e140 (37)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCAD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e34 (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66 (12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e32 (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e38 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.45\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e81 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e114 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e76 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e70 (18)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.58\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTobacco use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 (2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e25 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAlcohol abuse\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44 (8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e21 (6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.88\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eMedication\u003c/span\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAspirin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e90 (22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e149 (27)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e87 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e78 (21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.43\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClopidogrel\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e16 (4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e17 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.86\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eCOPD: chronic obstructive lung disease. CAD: coronary artery disease.\u003c/p\u003e\n\u003ch3\u003ePrimary Outcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome of the study was major bleeding, defined as a composite of esophageal bleeding, gastrointestinal (GI) bleeding, or nontraumatic intracranial bleeding at one-year and two-year follow-ups.\u003c/p\u003e\u003cp\u003eTwo well-matched cohorts of 381 patients each were created using a 1:1 propensity score matching model. Post-matching analysis revealed that patients who received warfarin had a higher overall frequency of major bleeding rate though the difference was not statistically significant at one year (9.7% vs. 7.6%, P\u0026thinsp;=\u0026thinsp;0.30) and two years (11.7% vs. 9.0%, P\u0026thinsp;=\u0026thinsp;0.23). Kaplan-Meier curves illustrating the overall bleeding rates at one year follow up presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eSubgroup analysis of bleeding at one-year follow-up revealed a higher GI bleeding rate in the warfarin group (9.2% vs. 7.1%, P\u0026thinsp;=\u0026thinsp;0.30), though this difference was not statistically significant. Similarly, the esophageal bleeding rate (2.6% vs. 2.6%, P\u0026thinsp;=\u0026thinsp;1.00) and nontraumatic intracranial bleeding rate (2.6% vs. 2.6%, P\u0026thinsp;=\u0026thinsp;1.00) were identical in both groups.\u003c/p\u003e\n\u003ch3\u003eSecondary Outcomes\u003c/h3\u003e\n\u003cp\u003eThe secondary outcomes of the study included the incidence of TIPS procedure, spontaneous bacterial peritonitis (SBP), and mortality.\u003c/p\u003e\u003cp\u003eThe rate of TIPS procedure frequency in the warfarin versus DOAC group was 3.7% vs. 3.7%, respectively (P\u0026thinsp;=\u0026thinsp;1.00) at one year and 3.4% vs. 4.8% (P\u0026thinsp;=\u0026thinsp;0.36) at two years, showing an increase in the DOACs group at the two-year follow-up but no significant difference between the groups.\u003c/p\u003e\u003cp\u003eThe incidence of SBP in the warfarin versus group was 3.4% vs. 2.6%, respectively (P\u0026thinsp;=\u0026thinsp;0.53) at one year and 3.4% vs. 2.7% (P\u0026thinsp;=\u0026thinsp;0.52) at two years, indicating higher frequency in the warfarin group, though this difference was not statistically significant.\u003c/p\u003e\u003cp\u003eSimilarly, overall mortality rates were higher in the warfarin group, with 11.0% vs. 8.4% (P\u0026thinsp;=\u0026thinsp;0.22) at one year and 13.8% vs. 11.4% (P\u0026thinsp;=\u0026thinsp;0.32) at two years, though these differences did not reach statistical significance. Kaplan-Meier curves illustrating the secondary outcomes at one year follow up presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study provides a real-world comparison of key components of safety and efficacy of direct oral anticoagulants (DOACs) versus warfarin in patients with Budd-Chiari Syndrome (BCS), a vascular liver disorder that necessitates lifelong anticoagulation to prevent disease progression and recurrent thrombosis [\u003cspan additionalcitationids=\"CR25\" citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. DOACs are increasingly being used in patients with liver disease and are generally considered safe in those with compensated hepatic function [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Notably, individuals with significant liver disease were excluded from Phase III DOAC trials [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e], limiting robust data on their safety in this population. However, emerging evidence suggests a heightened bleeding risk in individuals with more advanced liver disease [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Complexity of warfarin management is of concern in patients with hepatic dysfunction possibly warranting a greater frequency of laboratory testing in clinical practice.\u003c/p\u003e\u003cp\u003ePrior studies have reported notable bleeding rates among cirrhotic patients receiving DOACs, with Mort et al. [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] documenting a 21% bleeding incidence in patients with decompensated cirrhosis over a median follow-up of six months. Additionally, de Gottardi et al.[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] observed an overall bleeding rate of 13.9% in cirrhotic patients using DOACs over a median duration of seven months. Given these concerns, our findings indicating lower, albeit statistically non-significant, major bleeding rates with DOACs compared to warfarin in BCS patients provide valuable insight into their potential role as an alternative anticoagulation strategy. Further studies are warranted to confirm these observations and delineate the safety profile of DOACs in this unique population.\u003c/p\u003e\u003cp\u003eRates of transjugular intrahepatic portosystemic shunt (TIPS) procedures were similar between the DOAC and warfarin groups at both one- and two-year follow-ups. This finding suggests that anticoagulation choice may not significantly influence the need for invasive intervention in BCS. According to a retrospective cohort study conducted at the University of Pennsylvania, 44.7% of BCS patients received TIPS, with 90.5% of these patients also on anticoagulation [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Another study reported that 39.5% of patients underwent TIPS in a large prospective multicenter European study, with a median overall follow-up of 50 months [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Additionally, a study involving 124 BCS patients treated with TIPS across six European centers indicated that TIPS was a common intervention, although the exact percentage of patients on anticoagulation was not specified [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn contrast, our study demonstrated significantly lower rates of TIPS utilization, with only 3.7% of patients in both the warfarin and DOAC cohorts requiring the procedure at one year and 3.4% vs. 4.8% at two years. This discrepancy may reflect differences in patient selection, disease severity, or institutional management strategies. Unlike prior studies that reported higher TIPS rates, our findings suggest that early and effective anticoagulation, regardless of agent choice, may reduce the need for invasive intervention in carefully selected patients. While the slight increased frequency in TIPS procedures in the DOAC group at two years was not statistically significant (P\u0026thinsp;=\u0026thinsp;0.36), it raises questions about whether longer follow-up might reveal subtle differences in disease progression between anticoagulant groups. Ultimately, our results highlight the importance of individualized management in BCS and suggest that further research is needed to refine criteria for selecting patients who truly benefit from early TIPS placement.\u003c/p\u003e\u003cp\u003eGiven that TIPS is typically reserved for patients with progressive hepatic congestion and portal hypertension [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e], our results indicate that DOACs do not appear to increase the likelihood of requiring these procedures compared to warfarin. However, further studies evaluating hemodynamic differences between the two anticoagulation strategies would be valuable in confirming these findings.\u003c/p\u003e\u003cp\u003eIn our study, we found that the incidence of spontaneous bacterial peritonitis (SBP) was comparable between the DOAC and warfarin groups at both one- and two-year follow-ups, with rates of 3.4% vs. 2.6% respectively (P\u0026thinsp;=\u0026thinsp;0.53) at one year and 3.4% vs. 2.7% (P\u0026thinsp;=\u0026thinsp;0.52) at two years. Although there was a slightly higher SBP rate in the warfarin group, this difference was not statistically significant, aligning with previous studies suggesting that anticoagulation choice does not substantially impact SBP risk in BCS patients. These findings reinforce the assertion that SBP risk is likely driven more by the severity of liver disease and portal hypertension rather than the anticoagulation strategy itself. Given the complexity of SBP pathophysiology in BCS, future research incorporating liver disease severity scores, such as the Model for End-Stage Liver Disease (MELD) score or the Child-Pugh classification system, may help determine whether specific patient subgroups have differential risks based on anticoagulation type.\u003c/p\u003e\u003cp\u003eAlthough the overall mortality rate was slightly higher in the warfarin group compared to the DOAC group at both one and two years, this difference was not statistically significant. A study by Pavri et al. reported that among 47 BCS patients, 40 (85.1%) were on anticoagulation, with 30 (63.8%) maintained on warfarin. Over a median follow-up of 974 days, 10 patients (21.3%) died, indicating a significant mortality rate in this cohort [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Another study by Sharma et al. found that the 1-year and 5-year survival rates for BCS patients on anticoagulation were 94.2% and 87.5%, respectively, suggesting that long-term survival can be favorable with appropriate management [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The non-significance of mortality outcomes in our study suggests that neither anticoagulant provided a clear survival advantage in the studied cohort. However, given the retrospective nature of our study, potential confounders such as underlying liver dysfunction, thrombotic burden, and adherence to anticoagulation therapy must be considered when interpreting these results.\u003c/p\u003e\u003cp\u003eOur findings mirror prior research suggesting that while anticoagulation is essential in BCS management, survival outcomes are likely influenced by a complex interplay of patient-specific factors beyond the choice of anticoagulant. Given that DOACs are increasingly utilized in practice, further research is warranted to determine whether differences in drug metabolism, adherence, or hepatic function influence long-term outcomes in this patient population. Additionally, stratification based on liver disease severity or thrombotic burden may help elucidate whether certain subgroups could benefit more from one anticoagulation strategy over another.\u003c/p\u003e\u003cp\u003eOur study has several strengths. By leveraging the TriNetX database, a global research network encompassing diverse healthcare systems across multiple countries, our findings benefit from a broad and representative patient population, enhancing their generalizability. Additionally, our study methodology resulted in a robust sample size despite the rarity of this disorder, allowing for more precise estimates of outcomes and subgroup analyses. To further strengthen the validity of our results, we employed propensity score matching, minimizing the impact of confounding variables and ensuring a more balanced comparison between the DOAC and warfarin groups. This methodological rigor enhances the reliability of our conclusions and underscores the relevance of our findings in real-world clinical practice.\u003c/p\u003e\u003cp\u003eOn the other hand, the limitations of our study include the potential for residual confounding despite the use of propensity score matching. Second, we lacked data on the specific types and dosages of DOACs used, which may influence safety and efficacy outcomes. Third, the study population was drawn from a large global database, potentially introducing heterogeneity in clinical practices across different healthcare institutions. Lastly, follow-up duration was limited to two years, and longer-term outcomes remain unknown. Future research, particularly prospective studies with randomized designs would be the gold standard to further elucidate the role of DOACs in BCS management, however recognizing the challenge of such research present in rarer conditions such as this are potentially prohibitive Clinical registries that employ a multi-center approach may be a viable alternative to studying patient characteristics, treatment and outcomes over long periods and in real-world settings.\u003c/p\u003e\u003cp\u003eIn conclusion, our findings suggest that DOACs are a viable alternative to warfarin for BCS patients, demonstrating comparable safety and effectiveness. While the non-significant trend toward lower bleeding and mortality rates with DOACs is promising, additional research is needed to validate these findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the CAMC/WVU Charleston Division IRB Review Board under protocol number 24-1159\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Publish\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003edeclaration\u003c/strong\u003e: Not applicable.\u003c/p\u003e\n\u003ch3\u003eFunding\u003c/h3\u003e\n\u003cp\u003eThe authors received no financial support for the research, authorship, or publication of this article.\u003c/p\u003e\n\u003ch3\u003eAuthor Contribution\u003c/h3\u003e\n\u003cp\u003eN.A. conceived the study, designed the methodology, and conducted the data analysis. M.A. contributed to data acquisition, assisted in statistical analysis, and helped interpret the results. M.C. contributed to data interpretation and wrote the initial draft of the manuscript. E.D. and A.K. provided critical revision of the manuscript for important intellectual content and contributed to the clinical contextualization of findings. All authors reviewed and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eKi M, et al. Incidence, prevalence and complications of Budd-Chiari syndrome in South Korea: a nationwide, population-based study. Liver Int. 2016;36(7):1067\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGoel A, et al. A study of aetiology of portal hypertension in adults (including the elderly) at a tertiary centre in southern India. Indian J Med Res. 2013;137(5):922\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDarwish Murad S, et al. Etiology, management, and outcome of the Budd-Chiari syndrome. Ann Intern Med. 2009;151(3):167\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePerello A, et al. TIPS is a useful long-term derivative therapy for patients with Budd-Chiari syndrome uncontrolled by medical therapy. Hepatology. 2002;35(1):132\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCheng D, et al. Clinical features and etiology of Budd-Chiari syndrome in Chinese patients: a single-center study. J Gastroenterol Hepatol. 2013;28(6):1061\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eQi X, et al. Thrombotic risk factors in Chinese Budd-Chiari syndrome patients. An observational study with a systematic review of the literature. Thromb Haemost. 2013;109(5):878\u0026ndash;84.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGao X, et al. Risk factors of recurrence among 471 Chinese patients with Budd-Chiari syndrome. Clin Res Hepatol Gastroenterol. 2015;39(5):620\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDenninger MH, et al. Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. Hepatology. 2000;31(3):587\u0026ndash;91.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmarapurkar DN, Punamiya SJ, Patel ND. Changing spectrum of Budd-Chiari syndrome in India with special reference to non-surgical treatment. World J Gastroenterol. 2008;14(2):278\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDayal S, et al. Multilineage hemopoietic stem cell defects in Budd Chiari syndrome. J Hepatol. 1997;26(2):293\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePati HP, et al. Spectrum of hemostatic derangements, in Budd-Chiari syndrome. Indian J Gastroenterol. 2003;22(2):59\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMohanty D, et al. Hereditary thrombophilia as a cause of Budd-Chiari syndrome: a study from Western India. Hepatology. 2001;34(4 Pt 1):666\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang W et al. \u003cem\u003eBudd-Chiari Syndrome in China: A Systematic Analysis of Epidemiological Features Based on the Chinese Literature Survey.\u003c/em\u003e Gastroenterol Res Pract, 2015. 2015: p. 738548.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHitawala AA, Gupta V. \u003cem\u003eBudd-Chiari Syndrome\u003c/em\u003e, in \u003cem\u003eStatPearls\u003c/em\u003e. Treasure Island (FL); 2025.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCoilly A, et al. Budd-Chiari syndrome. Clin Res Hepatol Gastroenterol. 2020;44(4):420\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSharma A, et al. An Update on the Management of Budd-Chiari Syndrome. Dig Dis Sci. 2021;66(6):1780\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRautou PE, et al. Bleeding in patients with Budd-Chiari syndrome. J Hepatol. 2011;54(1):56\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDe Gottardi A, et al. Antithrombotic treatment with direct-acting oral anticoagulants in patients with splanchnic vein thrombosis and cirrhosis. Liver Int. 2017;37(5):694\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSemmler G, et al. Outcome of Budd-Chiari Syndrome Patients Treated With Direct Oral Anticoagulants: An Austrian Multicenter Study. Clin Gastroenterol Hepatol. 2023;21(4):978\u0026ndash;87. e2.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSharma S, et al. Dabigatran as an oral anticoagulant in patients with Budd-Chiari syndrome post-percutaneous endovascular intervention. J Gastroenterol Hepatol. 2020;35(4):654\u0026ndash;62.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSimonetto DA, et al. ACG Clinical Guideline: Disorders of the Hepatic and Mesenteric Circulation. Am J Gastroenterol. 2020;115(1):18\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ede Franchis R, et al. Baveno VII - Renewing consensus in portal hypertension. J Hepatol. 2022;76(4):959\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAmin N et al. Outcomes of Outpatient Elective Esophageal Varices Band Ligation in Cirrhosis Patients with Significant Thrombocytopenia. Diseases, 2025. 13(2).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEuropean Association for the Study of the Liver. Electronic address, e.e.e., \u003cem\u003eEASL Clinical Practice Guidelines: Vascular diseases of the liver\u003c/em\u003e. J Hepatol. 2016;64(1):179\u0026ndash;202.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eShukla A, et al. Budd-Chiari syndrome: consensus guidance of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int. 2021;15(3):531\u0026ndash;67.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNorthup PG, et al. Vascular Liver Disorders, Portal Vein Thrombosis, and Procedural Bleeding in Patients With Liver Disease: 2020 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021;73(1):366\u0026ndash;413.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDi Nisio M, et al. Anticoagulant therapy for splanchnic vein thrombosis: ISTH SSC Subcommittee Control of Anticoagulation. J Thromb Haemost. 2020;18(7):1562\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAgnelli G, et al. Apixaban for extended treatment of venous thromboembolism. N Engl J Med. 2013;368(8):699\u0026ndash;708.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eInvestigators E, et al. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med. 2010;363(26):2499\u0026ndash;510.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSemmler G, et al. Safety of direct oral anticoagulants in patients with advanced liver disease. Liver Int. 2021;41(9):2159\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMort JF, et al. Rates of Bleeding and Discontinuation of Direct Oral Anticoagulants in Patients With Decompensated Cirrhosis. Clin Gastroenterol Hepatol. 2021;19(7):1436\u0026ndash;42.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePavri TM, et al. Budd-Chiari syndrome: a single-center experience. World J Gastroenterol. 2014;20(43):16236\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSeijo S, et al. Good long-term outcome of Budd-Chiari syndrome with a step-wise management. Hepatology. 2013;57(5):1962\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGarcia-Pagan JC, et al. TIPS for Budd-Chiari syndrome: long-term results and prognostics factors in 124 patients. Gastroenterology. 2008;135(3):808\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSharma A, et al. Anticoagulating Budd-Chiari syndrome patients presenting with variceal bleed: A retrospective study. J Gastroenterol Hepatol. 2020;35(8):1397\u0026ndash;403.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"thrombosis-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"thrj","sideBox":"Learn more about [Thrombosis Journal](http://thrombosisjournal.biomedcentral.com/)","snPcode":"12959","submissionUrl":"https://submission.nature.com/new-submission/12959/3","title":"Thrombosis Journal","twitterHandle":"@Thrombosis_J","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-6481491/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6481491/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eAnticoagulation is the cornerstone treatment for all types of Budd-Chiari Syndrome (BCS), often requiring lifelong therapy. While heparin and warfarin have traditionally been the primary treatments, Warfarin carries a significant bleeding risk, highlighting the need for more tailored strategies. Recently, direct oral anticoagulants (DOACs) have emerged as a potential alternative. Though off-label for BCS, there is limited existing literature on their safety and efficacy, emphasizing the need for further research.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis study used the TriNetX database, a multicenter platform encompassing over 270\u0026nbsp;million patients from 120 healthcare organizations globally. The dataset included adults (\u0026ge;\u0026thinsp;18 years) diagnosed with BCS who received anticoagulation therapy with warfarin or DOACs between 2006 and 2024. Exclusion criteria included other systemic thrombosis, end-stage renal disease (ESRD), pregnancy, platelet counts\u0026thinsp;\u0026lt;\u0026thinsp;50\u0026times;10\u0026sup3;/\u0026micro;L, or malignant neoplasms of the liver or biliary system. Two cohorts were created: patients treated with warfarin versus those treated with DOACs within two weeks of BCS diagnosis. Propensity score matching (PSM) adjusted for confounders such as sex, ethnicity, antiplatelet use, smoking, and chronic diseases, creating well-matched groups. TriNetX's statistical platform was utilized to compare one-year and two-years outcomes, including major bleeding, transjugular intrahepatic portosystemic shunt (TIPS) procedures performed, spontaneous bacterial peritonitis (SBP), and mortality.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 15,245 patients diagnosed with BCS were identified, of whom 2,566 were treated with warfarin and 3,066 with any DOACs. PSM was used to create two 1:1 matched cohorts of 381 patients each. At the one-year follow-up, the rate of major bleeding in patients treated with warfarin compared to those treated with DOACs was 9.7% vs. 7.6% (P\u0026thinsp;=\u0026thinsp;0.30). The rates of TIPS procedures (3.7% vs. 3.7%, P\u0026thinsp;=\u0026thinsp;1) and SBP (3.4% vs. 2.6%, P\u0026thinsp;=\u0026thinsp;0.53) were similar between the groups. Similarly, overall mortality rates were higher in the warfarin group but not statistically significant (11.0% vs. 8.4%, P\u0026thinsp;=\u0026thinsp;0.22). At the two-year follow-up, major bleeding rates remained higher in the warfarin group, although the difference was not statistically significant (11.7% vs. 9.0%, P\u0026thinsp;=\u0026thinsp;0.23). The rates of TIPS procedures (3.4% vs. 4.8%, P\u0026thinsp;=\u0026thinsp;0.36) and SBP (3.4% vs. 2.7%, P\u0026thinsp;=\u0026thinsp;0.52) continued to show no significant differences between the groups.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis study found that DOACs were comparable in safety in terms of risk of bleeding and effectiveness in terms of frequency of need for TIP and frequency of SBP to warfarin for BCS patients. While warfarin-treated patients had slightly higher rates of major bleeding and mortality at one- and two-year follow-ups, the differences were not statistically significant. Rates of TIPS procedures and SBP were similar between groups. These findings suggest DOACs as a potential alternative to warfarin, offering patients the advantage of a reduced need for frequent laboratory monitoring required with warfarin and simplified medication management These findings support the need for longer term and broader studies to evaluate the safety and efficiency of DOACs in this unique population.\u003c/p\u003e","manuscriptTitle":"DOACs in Budd-Chiari syndrome: A real-world comparison from the TriNetX Global Collaborative Network","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 09:33:07","doi":"10.21203/rs.3.rs-6481491/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-13T19:08:16+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-13T13:28:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"94157117456514463253682868468533425283","date":"2025-09-30T02:12:37+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-09-28T15:31:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"58782676442451828620298991727320841871","date":"2025-09-17T04:02:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"299891781484722722737783641536424732824","date":"2025-09-15T13:10:03+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"289252180349675664100273927477227579237","date":"2025-09-13T14:11:16+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-11T09:16:32+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-25T13:36:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-25T13:31:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Thrombosis Journal","date":"2025-04-18T22:16:27+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"thrombosis-journal","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"thrj","sideBox":"Learn more about [Thrombosis Journal](http://thrombosisjournal.biomedcentral.com/)","snPcode":"12959","submissionUrl":"https://submission.nature.com/new-submission/12959/3","title":"Thrombosis Journal","twitterHandle":"@Thrombosis_J","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"ee0df4bd-da0c-43bc-9e75-127adf66bb46","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-19T03:39:15+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-22 09:33:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6481491","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6481491","identity":"rs-6481491","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}