Study Finds No Benefit of Drug Combination in Cirrhosis

A RECENT randomised clinical trial investigated whether the combination of simvastatin and rifaximin could prevent severe complications in patients with decompensated liver cirrhosis. Conducted across 14 European hospitals between January 2019 and December 2022, the double-blind, placebo-controlled phase 3 trial included 237 patients who were stratified according to Child-Pugh class B or C. Patients received either simvastatin (20 mg/d) plus rifaximin (1200 mg/d) or a placebo for 12 months alongside standard therapy. The study aimed to assess whether this combination therapy could reduce the incidence of severe cirrhosis-related complications, including acute-on-chronic liver failure, the need for liver transplantation, or death. Secondary outcomes examined included common cirrhosis complications such as ascites, hepatic encephalopathy, variceal bleeding, acute kidney injury, and infection.

The trial results revealed no significant differences between the treatment and placebo groups in terms of acute-on-chronic liver failure incidence (17.9% vs 14.2%; hazard ratio, 1.23; P = .52), transplant or death rates (18.8% vs 24.2%; hazard ratio, 0.75; P = .32), or overall cirrhosis complications (42.7% vs 45.8%; hazard ratio, 0.93; P = .70). The treatment group did not demonstrate any clear benefit in preventing disease progression, despite previous studies suggesting potential positive effects of these drugs in liver disease management.

Additionally, the incidence of adverse events was similar between groups (426 vs 419 events; P = .59), indicating that simvastatin and rifaximin did not pose an increased general safety risk. However, three patients in the treatment group (2.6%) developed rhabdomyolysis, a serious condition associated with muscle breakdown, highlighting a potential safety concern.

These findings suggest that combining simvastatin and rifaximin does not offer a clinically meaningful advantage in preventing severe complications in patients with decompensated cirrhosis. Given the lack of observed benefits, further research may be necessary to explore alternative therapeutic strategies for improving outcomes in this patient population. While simvastatin and rifaximin may have theoretical benefits in liver disease, this study does not support their routine use in preventing complications of decompensated cirrhosis.

Katie Wright, EMJ

Reference

Pose E et al. Simvastatin and Rifaximin in Decompensated Cirrhosis: A Randomized Clinical Trial. JAMA. Published online February 5, 2025. doi:10.1001/jama.2024.27441