‘No beneficial effects’ from simvastatin plus rifaximin for decompensated cirrhosis
Key takeaways:
- Patients who received simvastatin plus rifaximin experienced similar rates of complications as those treated with placebo.
- Incidence of adverse events was high in both treatment and placebo groups.
The addition of simvastatin plus rifaximin to standard therapy did not improve outcomes among patients with decompensated cirrhosis who were at high risk for clinical complications, according to a study published in JAMA.
“[Currently,] there are no useful treatments to prevent the development of severe complications of liver cirrhosis,” Elisa Pose, MD, fellow in the liver unit of the Hospital Clinic of Barcelona, and colleagues wrote. “Simvastatin and rifaximin have shown beneficial effects in liver cirrhosis.”
To determine whether treatment with simvastatin plus rifaximin (Xifaxan, Bausch Health), along with standard therapy, could reduce the occurrence of acute-on-chronic liver failure (ACLF) and other complications of decompensated cirrhosis, Pose and colleagues conducted a multicenter, parallel-group, placebo-controlled trial of 237 adult patients (mean age, 57 years; 72% men; 93% white) with decompensated cirrhosis who were recruited from 14 European hospitals between January 2019 and December 2022.
The researchers randomly assigned patients 1:1 to receive 20 mg simvastatin plus 1,200 mg rifaximin per day (n = 117) or identical-appearing placebo of both medications (n = 120) for 12 months in addition to standard therapy.
The primary outcome of the study was incidence of ACLF. Secondary outcomes included transplant or death, a composite endpoint of complications of cirrhosis — including ascites, hepatic encephalopathy, variceal bleeding, acute kidney injury and infection — and changes in MELD score.
The median follow-up was 365 days in the simvastatin plus rifaximin group (interquartile range [IQR], 365-369) and placebo group (IQR, 350-369).
Overall, 21 patients in the simvastatin plus rifaximin group presented with at least one episode of ACLF vs. 17 of those in the placebo group (HR = 1.23; 95% CI, 0.65-2.34), according to the researchers.
Further, a comparable number of patients in the simvastatin plus rifaximin and placebo groups died or received liver transplants (n = 22 vs. 29; HR = 0.75; 95% CI, 0.43-1.32) or developed at least one complication of cirrhosis other than ACLF (n = 50 vs. 55; HR = 0.93; 95% CI, 0.63-1.36).
At the end of the follow-up period, the researchers reported that the mean MELD score was 13 (standard deviation, 4.8) in the simvastatin plus rifaximin group and 12 (standard deviation, 3.6) in the placebo group (adjusted mean difference, –0.42; 95% CI, –1.27 to 0.42).
They noted that adverse events were common in both treatment groups, with the occurrence of 426 events in the simvastatin plus rifaximin group and 419 events in the placebo group.
“In this study, no beneficial effects of rifaximin on preventing ACLF or other complications was observed when given in combination with simvastatin,” the researchers wrote. “Our results therefore do not support the use of rifaximin in the management of patients with decompensated cirrhosis for indications other than prevention of recurrent hepatic encephalopathy.”
Pose and colleagues acknowledged several study limitations, including the low dose of simvastatin used in the study and the applicability of the findings to patients with less advanced cirrhosis.
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