Use of simvastatin plus rifaximin not supported in patients with decompensated cirrhosis
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Simvastatin plus rifaximin did not reduce progression to acute-on-chronic liver failure, complications from cirrhosis or risk for death in patients with decompensated cirrhosis, according to data presented at EASL Congress.
“Rifaximin prevents recurrent hepatic encephalopathy; however, it is not known whether it may have beneficial effects on other complications of cirrhosis,” Elisa Pose, MD, PhD, of the Liver Unit at the Clinical Hospital of Barcelona, said. “The effects of the combination of statins and rifaximin on the natural history of decompensated cirrhosis have not been investigated.”
She continued, “In a recent dose-finding study of the LiverHope Consortium, we found that in patients with decompensated cirrhosis, simvastatin 40 mg per day in combination with rifaximin was associated with an increased risk of rhabdomyolysis, whereas the dose of 20 mg per day of simvastatin appeared to be safe.”
In the multicenter, randomized, double-blind, placebo-controlled phase 3 LiverHope efficacy trial, Pose and colleagues sought to assess the efficacy of simvastatin plus rifaximin in halting progression to acute-on-chronic liver failure (ACLF) in patients with decompensated cirrhosis. Of 315 patients screened, 254 were randomly assigned to receive simvastatin 20 mg plus rifaximin 1,200 mg per day (n = 126) or placebo (n = 128) for 12 months.
Time to first episode of ACLF was the study’s primary endpoint. Other endpoints included transplant-free survival; a composite of ACLF, death and transplant; a composite of complications of cirrhosis; and adverse events.
The intention-to-treat and safety population included 117 participants in the treatment arm and 120 in the placebo arm.
According to results, 20 patients in the treatment arm developed ACLF compared with 13 in the placebo arm (HR = 1.73; 95% CI, 0.73-4.1), a difference that was not statistically significant. Pose noted that both arms followed “very similar trajectories” regarding time to first episode of ACLF.
In addition, the severity of ACLF episodes was not significantly different between treatment and placebo arms: ACLF I (8 vs. 9), ACLF II (9 vs. 2) and ACLF III (3 vs. 2). Of those who developed ACLF, there was no significant difference in mortality related to ACLF episodes between treatment (n = 8) and placebo arms (n = 7).
According to Pose, 15 patients in the treatment arm died or were transplanted during the treatment period compared with 19 in the placebo arm, also a difference that was not statistically significant.
“The combination of simvastatin 20 mg per day plus rifaximin 1,200 mg per day for 12 months was not associated with a reduction of ACLF, complications of cirrhosis or death,” Pose concluded. “Incidence of adverse events was similar in both groups; however, three patients treated with simvastatin plus rifaximin developed rhabdomyolysis.”
She added, “These results do not support the use of the combination of simvastatin plus rifaximin in patients with decompensated cirrhosis.”
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Pose E, et al. Abstract LBO-01: Simvastatin plus rifaximin to prevent ACLF in patients with decompensated cirrhosis. A randomized, double-blind, placebo-controlled, phase 3 trial: the Liverhope efficacy trial. Presented at: EASL Congress; June 21-24, 2023; Vienna (hybrid meeting).
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