The combination of simvastatin and rifaximin may not reduce the incidence of acute-on-chronic liver failure or improve survival in patients with decompensated cirrhosis, according to a recent study. 

In the multicenter, double-blind, placebo-controlled phase III trial, published in JAMA, researchers led by Elisa Pose, of the Liver Unit at the Hospital Clínic de Barcelona, and colleagues evaluated whether simvastatin combined with rifaximin could improve outcomes in patients with decompensated cirrhosis. They enrolled 237 patients across 14 European hospitals between January 2019 and December 2022. The patients with decompensated cirrhosis classified as Child-Pugh class B or C were randomly assigned to receive 20 mg of simvastatin plus 1,200 mg of rifaximin daily (n = 117), or matching placebo (n = 120) for 12 months. The primary endpoint was the incidence of acute-on-chronic liver failure (ACLF), with secondary outcomes including liver transplant or mortality and complications of cirrhosis such as ascites, hepatic encephalopathy, variceal bleeding, acute kidney injury, and infection.

At baseline, the mean age of participants was 57 years, and 72% were male. No statistically significant differences were observed between the treatment and placebo groups regarding the incidence of ACLF (17.9% vs 14.2%, hazard ratio [HR] = 1.23, 95% confidence interval [CI] = 0.65–2.34, P = .52), liver transplant or mortality (18.8% vs 24.2%, HR = 0.75, 95% CI = 0.43–1.32, P = .32), or the development of cirrhosis-related complications (42.7% vs 45.8%, HR = 0.93, 95% CI = 0.63–1.36, P = .70). The rate of adverse events was similar between thde groups (426 vs 419 events, P = .59), though rhabdomyolysis occurred in three patients (2.6%) in the simvastatin plus rifaximin group compared with none in the placebo group.

These findings indicated that the combination of simvastatin and rifaximin did not significantly reduce the incidence of ACLF or other complications of cirrhosis. The study did not demonstrate a clinical benefit of adding simvastatin and rifaximin to standard therapy in patients with decompensated cirrhosis.

Full disclosures can be found in the published study.