Statin-Antibiotic Combo Shows No Benefit for Decompensated Cirrhosis

Adding simvastatin and rifaximin to standard therapy for decompensated cirrhosis does not improve clinical outcomes, a double-blind phase III trial showed.

For the primary endpoint, no significant difference emerged for the development of acute-on-chronic liver failure between the group assigned to the statin plus antibiotic combination versus those taking placebo (17.9% vs 14.2%; HR 1.23, 95% CI 0.65-2.34, P=0.52), reported researchers led by Elisa Pose, MD, of the Hospital Clínic of Barcelona in Spain.

According to the findings in JAMA, the severity grade of acute-on-chronic liver failure was also similar between the treatment and placebo groups.

The rationale for using statins in cirrhosis is the reduced portal pressure seen with statin use in prospective studies and the beneficial effects on liver outcomes seen in retrospective studies, the authors noted.

However, “simvastatin plus rifaximin had no effect on transplant or death or incidence of other complications of cirrhosis,” Pose and co-authors wrote. “The rate of adverse events was similarly high in the two study groups.”

They suggested the reason for their findings could be related to differences in the populations evaluated, the duration of therapy, or the simvastatin dose used.

“However, our study did not show significant differences in the rate and severity of ACLF [acute-on-chronic liver failure] or in the most relevant complications of cirrhosis, including ascites, variceal bleeding, hepatic encephalopathy, bacterial infection, and acute kidney injury,” they wrote. “Finally, treatment with simvastatin plus rifaximin was not associated with an improvement in liver or kidney function tests or MELD [Model for End-Stage Liver Disease] score.”

The 237 participants were treated in 14 European hospitals from January 2019 to December 2022. The patients were mostly male (72%) and an average 57 years old, with alcohol-related cirrhosis the most common etiology (80%).

Patients with a severe liver impairment, hepatocellular carcinoma, or severe non-liver comorbidities were not included. The study also excluded those already taking or indicated to take rifaximin or statins, and those with an increased risk of adverse events for either.

In addition to standard therapy, 117 participants were randomly assigned to take 20 mg of simvastatin daily and 400 mg of rifaximin three times daily for 12 months. The other 120 participants received daily placebos, looking identical to the medication, for 12 months. Median treatment duration was 360 days, with 63% of patients completing the study protocol.

Follow-ups occurred at 1, 3, 6, 9, and 12 months, with treatment temporarily discontinued in those who developed acute-on-chronic liver failure or other complications of cirrhosis until post-recovery.

Secondary outcomes included transplant or death, or a composite endpoint of cirrhosis complications that included ascites, hepatic encephalopathy, variceal bleeding, acute kidney injury, and infection.

There was no significant difference in the incidence of transplant or death between those receiving the medications or placebo (18.8% vs 24.2%; HR 0.75, 95% CI 0.43-1.32, P=0.32). Incidence of complications of cirrhosis was not significantly different between the treatment and placebo groups (42.7% vs 45.8%, P=0.70), nor was the rate of hospitalizations (rate ratio 0.86, 95% CI 0.58-1.29).

Rates of adverse events were similar between the groups (P=0.59), but three patients receiving simvastatin and rifaximin (2.6%) developed rhabdomyolysis.

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