Comparative effectiveness of warfarin in cirrhotic patients with non-symptomatic portal vein thrombosis: a multicenter, randomized controlled trial

ABSTRACT

The effectiveness and risks of anticoagulant therapy in cirrhotic patients with non-symptomatic portal vein thrombosis (PVT) remain unclear. We conducted a multicenter, Zelen-designed randomized controlled trial to determine the effectiveness of warfarin in cirrhotic patients with non-symptomatic PVT during a one-year follow-up. In brief, 64 patients were 1:1 randomly divided into the anticoagulation group or the untreated group. The probability of recanalization was significantly higher in the anticoagulation group than those untreated in both ITT analysis (71.9% vs 34.4%, p = 0.004) and PP analysis (76.7% vs 32.4%, p < 0.001). Anticoagulation treatment was the independent predictor of recanalization (HR 2.776, 95%CI 1.307–5.893, p = 0.008). The risk of bleeding events and mortality were not significantly different. A significantly higher incidence of ascites aggravation was observed in the untreated group (3.3% vs 26.5%, p = 0.015). In conclusion, warfarin was proved to be an effective and safe as an anticoagulation therapy for treating non-symptomatic PVT in cirrhotic patients.

KEYWORDS:

• Portal vein thrombosis
• liver cirrhosis
• anticoagulation
• warfarin
• portal hypertension

Article highlights

• The effectiveness and risks of anticoagulation therapy in cirrhotic patients with non-symptomatic portal vein thrombosis (PVT) remain unclear.

• Current guidelines did not advocate for extending the duration of anticoagulation beyond 6 months.

• This was a multicenter, Zelen-designed randomized controlled trial to determine the comparative effectiveness of warfarin as the anticoagulation therapy in cirrhotic patients with non-symptomatic PVT.

• 64 patients were 1:1 randomly divided into the anticoagulation group or the untreated group.

• The probability of recanalization was significantly higher in the anticoagulation group than those untreated in both ITT analysis (71.9% vs 34.4%, p = 0.004) and PP analysis (76.7% vs 32.4%, p < 0.001).

• Anticoagulation treatment was the independent predictor of recanalization in both ITT population (HR 2.776, 95%CI 1.307-5.893, p = 0.008) and PP population (HR 3.842, 95%CI 1.823-8.095, p < 0.001).

• The risk of bleeding events and mortality were not significantly different between the two groups.

• A significantly higher incidence of ascites aggravation was observed in the untreated group in PP analysis (3.3% vs 26.5%, p = 0.015), verifying the effect of anticoagulation in alleviating portal hypertension.

• 34.4% of patients achieved complete recanalization 6 months after the commencement of anticoagulation, supporting that extending anticoagulation duration could offer potential benefits without increasing the likelihood of severe bleeding events.

Information resources

In recent years, new evidences have emerged to support the effect of anticoagulant therapy in PVT [7,13]. Despite an increased risk of minor bleeding, it was potentially counterbalanced by the understanding that PVT itself contributed to a severe prognosis [17,18]. Notably, a prior randomized trial highlighted the beneficial impact of enoxaparin prophylaxis in preventing PVT and improving survival in patients with advanced cirrhosis [19]. Current studies now seek to further evaluate the role of anticoagulation in the prevention of PVT in cirrhosis (CIRROXABAN trial).

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers in this manuscript have no relevant financial or other relationships to disclose.

Author contributions

J Wang and S Chen designed the study. S Lu and Jie Chen performed the research and wrote the paper. P Xu, H Ding, B Wu, Y Shi, C Liu and Y Mu gave critical assistance in the research. R Zhang, L Ma, T Luo and X Zeng gave a critical revision of the article. All authors have read and approved the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/17474124.2024.2307575.

Additional information

Funding

This paper was funded by Science and Technology Commission of Shanghai Municipality[15411950501], the WBE Liver Foundation (2022015) and Shanghai Municipal Health Commission[202340180].