Reduce Dose of Apixaban Vs. Standard of Care for Secondary Prevention in Cirrhotic Patients with Chronic Portal Vein Thrombosis
Authors: Serra Carrera Marina , Simón-Talero Macarena , Campoy Desiree , Artaza Gonzalo , Perez Lafuente Mercedes , Camarillas Sergi , Muzio Sofia Laura , Mendez Jonay , Landwehr Maria , Bosch Francesc , Olivera Pável E 
Published: December 2024

Background. Portal vein thrombosis (PVT) is a common complication of advanced liver cirrhosis that negatively affects the course of liver disease, prognosis of cirrhotic patients and success of liver transplantation. Anticoagulation remains the primary intervention for acute symptomatic PVT; however, its efficacy and safety in chronic PVT management are not well-defined. Current standard-of-care treatments include vitamin K antagonists (VKAs) and low-molecular-weight heparin, which have established roles in PVT management but pose challenges related to monitoring and adverse effects. In the last decade, direct oral anticoagulants (DOACs) such as Apixaban have been introduced for thromboembolic disease prophylaxis and treatment. Despite their advantages, the clinical data supporting DOAC use in cirrhotic patients with PVT are limited.

Aim. To assess the effectiveness and safety of reduce dose of Apixaban compared to a cohort of VKA-treated patients for the secondary prevention (SP) of PVT. The effectiveness outcome was defined by recurrent/progression PVT. The safety outcome was defined by a first event of major bleeding, clinically relevant nonmajor bleeding, or all-cause death.

Methods. Unicenter, observational, and retrospective study, conducted between 2018 and 2023, enrolled patients over 18 years old with non-malignant portal vein thrombosis (PVT) who had completed 3-6 months of standard anticoagulant therapy. These patients transitioned to secondary prevention with either a reduced dose of Apixaban (2.5 mg twice daily) or vitamin K antagonists targeting an INR of 2-3. Exclusion criteria were malignant PVT and insufficient clinical data at PVT diagnosis or follow-up. We collected demographic, laboratory, and clinical data, including ascites and hepatic encephalopathy assessments using the Child-Pugh score at diagnosis and follow-up. Clinical progression during anticoagulation and its correlation with CT and MRI findings were reviewed by a multidisciplinary committee of hematologists, hepatologists, and interventional radiologists. The follow-up period, lasting at least 12 months, included assessments of recurrent PVT, major bleeding, non-major but clinically relevant bleeding (NMCR), and mortality.

Results. The study included 498 patients (54.6% women, mean age 56.6±19.1 years). Of these, 268 were treated with vitamin K antagonists (VKAs) (INR: 2-3, mean TTR: 59%), and 230 were treated with Apixaban (2.5 mg twice daily) (58.7% women). The mean follow-up from the initiation of secondary prevention to the last visit was 26.5±14.5 months. A significant proportion of patients (67%) had a Child-Pugh score of B or C.

Patients treated with VKAs had a higher rate of PVT recurrences/progression (6.7% vs. 2.1%; P &lt; 0.003) and major bleeding (8.2% vs. 1.7%; P &lt; 0.001) compared to those treated with Apixaban. In the VKA group, the risk of bleeding was associated with a platelet count of less than 50x10^3/mm^3 (OR=8.266; 95% CI: 2.310-39.211; p=0.002) and a TTR &lt;50% (HR=1.726; 95% CI: 1.310-2.511; p=0.002). Survival rates were better in the Apixaban group (88.4% vs. 68.7% at 2 years and 92.7% vs. 77.8% at 1 year; p=0.038). Multivariable analysis adjusted for competing risks revealed that cirrhotic patients on VKAs had an increased risk of major bleeding (Hazard Ratio, HR 1.816; 95% CI: 1.392-2.190) and progression of PVT (HR 1.543; 95% CI: 1.126-1.942)

Conclusions. In cirrhotic patients with chronic portal PVT, VKAs were associated with a 5-fold higher rate of PVT recurrences/progression and a 3-fold higher rate of major bleeding compared to reduced-dose Apixaban. Additionally, survival was better in the Apixaban group. These findings suggest that reduced-dose Apixaban is a safer and more effective option for SP in this population. Further prospective studies are needed to confirm these results.