Simvastatin addition to standard of care improves long-term survival in patients with cirrhosis after variceal bleed: An open label randomized controlled trial.

BACKGROUND AND AIMS

There is limited evidence about efficacy and safety of simvastatin in decompensated cirrhosis. We assessed whether addition of simvastatin to standard-of-care improves long-term survival in patients with cirrhosis after variceal bleeding.

DESIGN

This was a single-centre open-label randomised controlled trial with superiority design. Patients with cirrhosis (Child-Pugh score 5-12) were randomly assigned to receive either simvastatin20mg once-daily or no drug(n=138) in addition to standard therapy (carvedilol and band ligation) at day-5 of variceal bleeding episode. Primary outcome was all-cause mortality over 24-month follow-up. Secondary outcomes included individual complications of cirrhosis with death before decompensation as a competing event.

RESULTS

Baseline characteristics were similar in both groups with a mean age of 45.0±11.5 years and alcohol(48%) being the predominant aetiology. Most patients were of Child-Pugh A(34%) and B(50%) stage. Twenty-four patients(18%) on simvastatin and 44(31%) on standard therapy died over follow-up[hazard-ratio(HR) for simvastatin: 0.48[95%CI:0.29-0.81;p=0.006) with similar results on intention to treat and on per-protocol analysis(excluding 17 patients who stopped simvastatin). Incidence of ascites(sub-distributional HR):0.60[0.39-0.92] and spontaneous bacterial peritonitis (sHR:0.30[0.11-0.81] was lower in simvastatin arm. All cause decompensation(sHR:0.74[0.52-1.05]), rebleeding(sHR:0.87[0.57-1.34]), hepatic encephalopathy(sHR:0.71[0.42-1.19) and acute-on-chronic liver-failure (sHR:0.65[0.39-1.10]) were comparable in both arms. No heterogeneity of treatment-effect was demonstrated across CTP-class(p=0.105) or aetiology(p=0.39). Incidence of serious adverse events was similar[43% in simvastatin and 52% in standard therapy, absolute risk difference:[9.1%(-2.9 - 21.0%)].

CONCLUSION

Simvastatin may be associated with improved survival in selected patients with cirrhosis after variceal bleed and reduced incidence of new onset/refractory ascites and its complications [CTRI/2022/07/044263].