Rivaroxaban to prevent complications of portal hypertension in cirrhosis: The CIRROXABAN study

Abstract

Background & Aims Previous studies suggest that anticoagulation may reduce the risk of portal hypertension (PHT)-related complications and improve survival in patients with cirrhosis. This study aimed to evaluate the efficacy and safety of the direct oral anticoagulant rivaroxaban in patients with cirrhosis. Methods This was a randomized, double-blind, placebo-controlled, multicenter trial involving patients with cirrhosis, PHT, and moderate liver dysfunction (Child-Pugh score 7–10). Participants received either rivaroxaban 10 mg daily or placebo for 24 months. The primary composite endpoint was the development of a PHT-related complication or death/liver transplantation, whichever occurred first. Analyses were conducted using both modified intention-to-treat and per-protocol approaches. Results A total of 90 patients were enrolled (49 placebo, 41 rivaroxaban). After a median follow-up of 10.1 months, 34 patients reached the primary endpoint: 23 (46.9%) in the placebo group vs . 11 (26.8%) in the rivaroxaban group. The cumulative probability of survival free from the primary endpoint at 1 and 2 years was 54.4% and 43.0% in the placebo group, compared to 78.7% and 67.1% in the rivaroxaban group (log-rank p = 0.058). In a post hoc analysis of patients with Child-Pugh B7 scores (n = 55), rivaroxaban showed a potentially beneficial effect (hazard ratio 0.258; 95% CI 0.074–0.900). In the per-protocol analysis (41 placebo, 37 rivaroxaban), the primary event occurred in 19 patients (46.3%) in the placebo group vs. 9 (24.3%) in the rivaroxaban group (hazard ratio 0.463; 95% CI 0.209–1.024). Non–PHT-related bleeding events were more frequent in the rivaroxaban group (36.6% vs . 14.3%; relative risk 2.56; 95% CI 1.16–5.67). However, there were no significant differences in major bleeding events. Conclusions In patients with cirrhosis and moderate liver dysfunction, rivaroxaban may improve PHT complication-free survival without significantly increasing the risk of major bleeding. Impact and implications This study provides novel evidence supporting the potential use of rivaroxaban to prevent liver decompensation in patients with cirrhosis and portal hypertension. The observed reduction in decompensation events is consistent with previous findings on the benefits of anticoagulation in cirrhosis, suggesting a possible therapeutic role for rivaroxaban in this population. Although the reduction in the primary endpoint did not reach statistical significance in the overall cohort, a potential benefit was observed in a post hoc analysis of patients with Child-Pugh B cirrhosis. However, these findings should be interpreted with caution given the exploratory nature of the subgroup analyses. Non–portal hypertension-related bleeding events were more frequent in patients receiving rivaroxaban, though severe bleeding events were not increased. These results highlight the need for further studies to determine optimal dosing strategies that balance efficacy with bleeding risk. ClinicalTrials.gov NCT02643212. EudraCT Number 2014-005523-27.