Meta-analysis: The safety and efficacy of vaptans (tolvaptan, satavaptan and lixivaptan) in cirrhosis with ascites or hyponatraemia

Abstract

Background Vaptans may correct hyponatraemia and mobilise ascites through an increased excretion of water. The effect on clinical outcomes is debated. Aim To determine the effects of vaptans (tolvaptan, satavaptan and lixivaptan) on patients with cirrhosis and hyponatraemia or ascites. Methods Systematic review of randomised controlled trials. The primary outcome measure was mortality. Electronic and manual searches were combined (April 2012). Data were extracted from published reports, online information from the Food and Drug Administration website or obtained through correspondence with authors and pharmaceutical companies. The primary meta-analyses were performed using random effects models due to an expected clinical diversity. Results Twelve trials with a total of 2266 patients were included. Randomisation was adequate in all trials. Eight trials were double-blind. Random effects meta-analyses found no clear differences between vaptans and control groups regarding mortality (RR = 1.06, 95% CI = 0.90-1.26, I2 = 0%), variceal bleeding, hepatic encephalopathy, spontaneous bacterial peritonitis, hepatorenal syndrome, or renal failure. Vaptans increased serum sodium levels (WMD = 1.8 mmol/L, 95% CI = 0.79-2.96) and lead to reductions in weight and the time to the first paracenthesis. Vaptans increased the risk of adverse events (RR = 3.97, 95% CI = 1.78-8.83), including an excessive urine volume (RR = 9.96, 95% CI = 1.38-71.68). Conclusions Vaptans have a small beneficial effect on hyponatraemia and ascites, but do not affect mortality, complications to cirrhosis or renal failure. The data do not support the routine use of vaptans in cirrhosis. © 2012 Blackwell Publishing Ltd.