Curative Effect and Safety of Tolvaptan Combined with Traditional Diuretics in Treatment of Patients with Cirrhotic Ascites and Relevant Research on its Dose: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

Abstract

Background Tolvaptan is a receptor antagonist of highly selective vasopressin V2, and it can promote excretion of water without electrolyte.Aims To evaluated curative effect and safety of Tolvaptan in treatment of cirrhotic ascites, and its relationship with drug dose.Methods Computer retrieval of PubMed, EMbase and The Cochrane Library was carried out to search the clinical trials of cirrhotic ascites treatment by Tolvaptan. The time limit of retrieval is from the database setup to May 31, 2019. 2 researchers independently screened studies, extracted the data and crosschecked. RevMan 5.3 software was used for Meta-analysis.Results Finally, 6 articles and 848 patients were included in the study. Meta-analysis indicates that after the intervention for 7 days, serum sodium ion concentration of the combined diuretic group obviously increased, compared with the traditional diuretic group (WMD=2.92mmol/L, 95%CI [2.15, 3.70], P<0.001). In addition, Tolvaptan also can decrease patients’ ascites amount through increasing liquid discharge. However, the drug dose has no obvious correlation with the reduction degree of ascites amount. The rise of blood uric acid is the major adverse event in the treatment of cirrhotic ascites patients by Tolvaptan (OR=6.01, 95%CI [1.11, 32.56], P=0.04). When the dose of Tolvaptan rose to 15mg or 30mg, the total incidence of adverse events was obviously higher than it of traditional diuretic group.Conclusion Tolvaptan combined with traditional diuretics has good curative effect for the patients with cirrhotic ascites. As its adverse reactions, the recommended dose of Tolvaptan is 7.5mg in the combined therapy.Registration number: The meta-analysis was registered prospectively on the PROSPERO database (ID: CRD42019143480).