Decompensated cirrhosis: low-dose simvastatin appears safe with rifaximin

Takeaway

• Simvastatin 20 mg/day plus rifaximin appears safe in patients with decompensated cirrhosis and will be used in the phase 3 LIVERHOPE_EFFICACY study.
• The 40 mg/day dose was associated with increased risks for liver/muscle toxicity.

Why this matters

• Recent studies have suggested that statins may attenuate cirrhosis progression and reduce risk for hepatocellular carcinoma.
• Rifaximin is indicated to reduce risk for hepatic encephalopathy.

Study design

• European phase 2 randomized LIVERHOPE-SAFETY trial of 44 patients with decompensated cirrhosis and moderate-severe liver failure.
• Participants received rifaximin 1200 mg/day with simvastatin (40 or 20 mg/day) or placebo only for 12 weeks.
• Funding: Horizon 20/20 European programme.

Key results

• 40 mg/day simvastatin was stopped for safety reasons after 10 patients completed treatment.
• At last visit, 40 mg/day simvastatin was associated with significant increases vs placebo in:
  • Aspartate aminotransferase (AST: mean Δ, 130 IU/L; P=.0009);
  • Alanine aminotransferase (ALT: mean Δ, 61 IU/L; P=.0025); and
  • Creatine kinase (mean Δ, 1009 IU/L; P=.014).
• 20 mg/day simvastatin and placebo yielded similar levels of AST (P=.728), ALT (P=.698), and creatine kinase (P=.992).
• Liver/muscle toxicity consistent with rhabdomyolysis occurred in 3 patients (18.8%) receiving 40 mg/day simvastatin.
• Simvastatin 40 mg/day was associated with a higher adverse event discontinuation rate than 20 mg/day or placebo (56% vs 14% and 14%; P=.017).

Limitations

• Small sample size.