Tolvaptan Response Improves Overall Survival in Patients with Refractory Ascites: A Meta-Analysis

Abstract

Background and Aims: Refractory ascites represents a significant complication of decompensated cirrhosis, associated with increased mortality rates. The aim of this meta-analysis was to evaluate whether response to treatment with tolvaptan is associated with improved overall survival in cirrhotic patients with refractory ascites. Methods: Medline, Scopus, Cochrane Central Register of Controlled Trials, Clinicaltrials.gov, and Google Scholar databases were systematically searched from inception to April 11, 2019. All studies that assessed the overall survival of patients with ascites depending on their response to tolvaptan were held eligible. Results: Nine studies were included, with a total of 736 patients with cirrhosis and ascites. Response to tolvaptan was estimated to be linked to significantly improved overall survival (hazard ratio [HR] 0.42, 95% CI [0.31-0.58]). Subgroup analysis indicated that the same outcome was present when tolvaptan responsiveness was defined either as effective body weight loss (HR 0.44, 95% CI [0.30-0.63] or as effective sodium restoration (HR 0.35,]. Sensitivity analysis suggested that the presence of hepatocellular carcinoma, the sample size, and the quality of the studies did not significantly affect the overall result of the meta-analysis. Conclusions:The outcomes of the meta-analysis support the prognostic role of tolvaptan response in patients with cirrhosis and refractory ascites, as it was shown to lead to significantly improved overall survival. These findings should be confirmed by future large-scale studies, while efficient biomarkers should be identified in order to accurately predict response to tolvaptan and discriminate patients that would benefit from its administration.

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

“…Early meta studies for Vaptan drugs (including Tolvaptan, Satavaptan and Lixivaptan) reported that Vaptan drugs was not associated with prolonged survival in patients with cirrhosis [11][12]. In contrast, a recent meta analysis based on retrospective studies showed that Tolvaptan significantly improves overall survival in patients with cirrhosis and refractory ascites, but this paper has not a high level of evidence [13]. Due to the good efficacy and safety of 7.5 mg Tolvaptan demonstrated in this study, more RCT studies to study Tolvaptan and survival rates in patients with cirrhotic ascites should be performed to support the prognostic role of tolvaptan.…”

“…The complications caused by Tolvaptan also receive much attention, apart from the good curative effect. Existing RCT researches report the daily application of low-dose Tolvaptan (7.5 mg or 15 mg) promotes 6-month survival rate of patients with cirrhotic ascites [21], and a latest meta analysis also reported that Tolvaptan could significantly improve overall survival [13]. However, the concrete complications in the use process are not verified by lots of data.…”

“…At present, there are only a few meta-analyses for vaptans drugs (including Tolvaptan, Satavaptan and Lixivaptan), and there are very little results about Torvalptan, let alone a comprehensive analysis on the efficacy and safety of Torvalptan [11,12]. A most recent meta analysis for retrospective cohort studies of Tolvaptan reported total survival after application, but no detailed data were available on treatment outcomes and complications [13]. Besides, we found a meta analysis for Tolvaptan (in Chinese) [14], but most (5/8) of the studies included were single-center clinical trials published in Chinese journals.…”

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

“…In addition to the good curative effect, complications caused by torvatan are also of great concern. Existing RCT researches report the daily application of low-dose Tolvaptan (7.5mg or 15mg) promotes 6-month survival rate of patients with cirrhotic ascites [21], and a latest meta analysis also reported that Tolvaptan could signi cantly improve overall survival rate [13]. However, the concrete complications in the use have not been con rmed by a large number of data.…”

“…Currently, there are only a few meta-analyses for vaptans drugs (including Tolvaptan, Satavaptan and Lixivaptan), and few results on Tolvaptan, not to mention a comprehensive analysis on the e cacy and safety of Tolvaptan [11,12]. A recent meta analysis for retrospective cohort studies of Tolvaptan reported total survival after application, but no detailed data were available on treatment outcomes and complications [13]. Moreover, we found a meta analysis for Tolvaptan (in Chinese) [14], but most (5/8) of the studies included were single-center clinical trials published in Chinese journals.…”