Simvastatin Addition to Standard of Care Improves Long-Term Survival in Patients With Cirrhosis After Variceal Bleed: An Open Label Randomized Controlled Trial.

Abstract

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. This was a single-center open label randomized controlled trial with superiority design. Patients with cirrhosis (Child-Pugh score 5-12) were randomly assigned 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. 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. Baseline characteristics were similar in both groups with a mean age of 45.0 ± 11.5 years and alcohol (48%) being the predominant etiology. 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% confidence interval 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 (subdistributional HR [sHR]) 0.60 (0.39-0.92) and spontaneous bacterial peritonitis (sHR 0.30 [0.11-0.81]) was lower in the 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 Child-Turcotte-Pugh class ( P = 0.105) or etiology ( 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% to 21.0%]). 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).