Addition of Simvastatin to Carvedilol and Endoscopic Variceal Ligation improves rebleeding and survival in patients with Child-Pugh A and B class but not in Child Pugh C class

Abstract

Background: Even with current standard treatment after variceal bleeding which includes combination of nonselective b-blockers and repeated endoscopic variceal ligation, the risk of rebleeding and mortality are high. Statins exhibit an antifibrotic effect and improves HVPG. We evaluated whether addition of simvastatin to carvedilol plus EVL therapy reduces variceal rebleeds or death in patients with cirrhosis. Method: Patients with a variceal bleed 5 to 10 days before were randomly assigned to groups A [carvedilol (n = 69)] or group B [carvedilol (maximum dose - 12.5mg), and simvastatin (40mg/day) (n = 65)]. Primary end points were variceal rebleeding or death. Secondary end points were new complications of portal hypertension and serious adverse effects of drugs. Results: During a mean follow-up of 49.05 ± 25.74 weeks, composite end point i.e. rebleeding or death developed in 23 patients (33.3%) in group A and 12 patients (18.5%) in group B [HR for simvastatin = 0.512; 95% CI: 0.254 – 1.030; p = 0.06]. In subgroup analysis by excluding patients of Child C class, 18 patients (34.6%) in group A and 7 patients (13.6%) in group B developed composite end point [HR for simvastatin = 0.369; 95% CI: 0.154 – 0.887; p = 0.026]. 17.4% and 15.4% patients in group A and B developed additional secondary complication [HR = 0.86; 95% CI: 0.345-2.161; p = 0.75). No simvastatin induced significant adverse effects were found. Conclusion: Addition of simvastatin to carvedilol and EVL may reduce the rebleeding and death in patients with less advance liver disease.