Effects of tolvaptan add-on therapy in patients with acute heart failure: meta-analysis on randomised controlled trials

OBJECTIVES: Treating acute decompensated heartfailure (ADHF) for improving congestion with diuretics may cause worsening renal function (WRF), but the clinical efficacy of tolvaptan add-on therapy on reducing WRF in ADHF patients is inconsistent. This analysis is to evaluate the effects of tolvaptan add-on therapy on reducing WRF in ADHF patients. METHODS: Meta-analysis of randomised trials of tolvaptan add-on therapy on reducing WRF in ADHF patients. The MEDLINE, Embase and Cochrane Central Register of Controlled Trials databases were searched for relevant articles from their inception to 31 October, 2017. Two reviewers filtrated the documents on WRF, short-term all-cause mortality, body weight decreased, elevated sodium level for calculating pooled relatives risks, weighted mean difference and associated 95% CIs. We used fixed-effects or random-effects models according to I(2) statistics. ACHIEVEMENTS: Seven random controlled trials with 937 patients were included for analysis. Compared with the control, tolvaptan add-on therapy did not improve incidence of worsening renal function (RR 0.78, 95% CI 0.48 to 1.26, p=0.31, I(2)=66%) and short-term all-cause mortality (RR 0.85, 95% CI 0.47 to 1.56, p=0.61, I(2)=0%). On subgroup analyses, there was a suggestion of possible effect modification by dose of tolvaptan, in which benefit was observed in low-dose (≤15 mg/day) group (RR 0.48, 95% CI 0.23 to 1.02, p=0.05, I(2)=54%), but not with high-dose (30 mg) group (RR 1.33, 95% CI 0.99 to 1.78, p=0.05, I(2)=0%). However, tolvaptan add-on therapy reduced body weight in 2 days (standardised mean difference −0.49, 95% CI −0.64 to −0.34, p<0.00001, I(2)=0%), increased sodium level (mean difference 1.56, 95% CI 0.04 to 3.07, p=0.04, I(2)=0%). CONCLUSION: The result suggests that comparing with the standard diuretic therapy, tolvaptan add-on therapy did not reduce the incidence of WRF and short-term mortality, however, it can decrease body weight and increase the sodium level in patients who are with ADHF. Further researches are still required for confirmation.