Simvastatin extends survival in patients with cirrhosis after variceal bleed

Treatment with simvastatin appears to improve survival in some patients with cirrhosis after variceal bleed, suggests a study. The drug also reduces the incidence of new-onset, refractory ascites and its complications.

A team of investigators conducted this single-centre, open-label, randomized controlled trial with superiority design. They randomly assigned patients with cirrhosis (Child-Pugh score 5‒12, mean age 45.0 years) to receive either simvastatin 20 mg once daily (n=130) or no drug (n=138) in addition to standard therapy (carvedilol and band ligation) at day 5 of variceal bleeding episode.

All-cause mortality over 24-month follow-up was the primary outcome, while individual complications of cirrhosis with death before decompensation as a competing event served as secondary outcomes.

Both treatment groups had similar characteristics at baseline and had alcohol as the predominant aetiology. Of the patients, 34 percent had Child-Pugh A stage and 50 percent had B stage.

During follow-up, 24 patients (18 percent) on simvastatin and 44 (31 percent) on standard therapy had died (hazard ratio [HR] for simvastatin, 0.48, 95 percent confidence interval [CI], 0.29‒0.81; p=0.006), with similar results on intention-to-treat and on per-protocol analyses (with the exclusion of 17 patients who discontinued treatment with simvastatin).

Patients on simvastatin had a lower incidence of ascites (subdistributional HR [sHR], 0.60, 95 percent CI, 0.39‒0.92) and spontaneous bacterial peritonitis (sHR, 0.30, 95 percent CI, 0.11‒0.81). However, no significant between-group differences were observed for all-cause decompensation (sHR, 0.74, 95 percent CI, 0.52‒1.05), rebleeding (sHR, 0.87, 95 percent CI, 0.57‒1.34), hepatic encephalopathy (sHR, 0.71, 95 percent CI, 0.42‒1.19), and acute-on-chronic liver failure (sHR, 0.65, 95 percent CI, 0.39‒1.10).

Heterogeneity of treatment effect was not seen across Child-Turcotte-Pugh class (p=0.105) or aetiology (p=0.39). With regard to safety, the incidence of serious adverse events did not differ significantly between treatment groups (43 percent in simvastatin vs 52 percent in standard therapy; absolute risk difference, 9.1 percent, 95 percent CI, ‒2.9 to 21.0).