The Efficacy and Safety of Tolvaptan in Patients with Hyponatremia: A Meta-Analysis of Randomized Controlled Trials

Background and Objectives Comprehensive evaluations regarding the benefits of tolvaptan in the treatment of hyponatremia are lacking. The objective of this meta-analysis was to assess the efficacy and safety of tolvaptan in patients with hyponatremia. Methods Pertinent studies were identified by searching PubMed, EMBASE, Web of Science, and the Cochrane Library for articles published between their respective inception dates and 31 April 2016. Summary relative risks (RRs) or weighted mean differences (WMDs) with their 95 % confidence intervals (CIs) were calculated using fixed-effects or randomized-effects models, depending on the degree of heterogeneity noted among the studies included in the analysis. Results Eleven articles comprising 5209 patients were ultimately included in the analysis. Our pooled results showed that tolvaptan was more effective than control with respect to increasing serum sodium concentrations (WMD = 3.99 mEq/L), 95 % CI 2.80-5.19, Z = 6.56, P < 0.001), improving serum sodium correction rates (RR = 3.35, 95 % CI 1.93-5.82, Z = 4.31, P < 0.001), improving 24-h urine output (WMD = 987.64 mL, 95 % CI 850.71-1124.57, Z = 14.14, P < 0.001), and improving net fluid balance (WMD = 795.97 mL, 95 % CI 418.56-1173.38, Z = 4.13, P < 0.001). Tolvaptan treatment also resulted in increased incidences of adverse events compared with control treatment (RR = 1.05, 95 % CI 1.02-1.07, Z = 3.83, P < 0.001). These events included dry mouth (RR = 2.38, 95 % CI 1.41-4.04, Z = 3.23, P = 0.001), thirst (RR = 3.85, 95 % CI 1.96-7.57, Z = 3.92, P < 0.001), pollakiuria (RR = 2.47, 95 % CI 1.41-4.33, Z = 3.16, P = 0.002), and overly rapid hyponatremia correction (RR = 8.43, 95 % CI 1.06-66.96, Z = 2.02, P = 0.04). No significant differences in all-cause mortality (RR = 0.99, 95 % CI 0.90-1.10, Z = 0.17, P = 0.86), serious adverse event rate (RR = 1.01, 95 % CI 0.80-1.29, Z = 0.11, P = 0.92), systolic blood pressure (WMD = 0.1 mmHg, 95 % CI -1.04 to 1.23, Z = 0.17, P = 0.87), or heart rate (WMD = -0.16 bpm, 95 % CI -1.14 to 0.82, Z = 0.31, P = 0.76) were noted between the two groups, based on the results of our meta-analysis. Conclusion The results of this meta-analysis suggest that tolvaptan can increase serum sodium concentrations, serum sodium correction rates, 24-h urine output, net fluid balance, and total adverse event rates without significantly decreasing all-cause mortality rates or increasing serious adverse event rates in patients with hyponatremia.