Effects of tolvaptan on volume overload in patients with heart failure: Meta-analysis of randomized controlled trials

The present meta-analysis aimed to evaluate effects of tolvaptan on fluid retention in patients with heart failure who were non-responsive to conventional treatment and to assess differences between effects of low (≤ 15 mg/day) and high (> 15 mg/day) tolvaptan doses. Randomized controlled trials comparing add-on tolvaptan therapy and placebo or therapy with other diuretics in patients with heart failure were identified through a database search. The primary outcomes were changes in body weight and urine volume, and the secondary outcomes were changes in serum sodium and creatinine levels. In total, 14 reports were analyzed using a random effects model. Add-on tolvaptan was associated with increased urine volume [mean difference (MD), 1.44 L; 95% confidence interval (CI), 0.96 to 1.92], decreased body weight (MD, −0.99 kg; 95% CI, −1.24 to −0.74), and increased serum sodium levels (MD, 3.66 mEq/L; 95% CI, 3.43 to 3.88) within 2 days. Serum creatinine levels on day 7 were not different between the groups (MD, −0.03 mg/dL; 95% CI, −0.09 to 0.03). The high-dose group showed greater changes in urine volume, body weight, and serum sodium levels than the low-dose group. Serum creatinine levels slightly increased in the high-dose group (MD, 0.06; 95% CI, 0.04 to 0.08) and slightly decreased in the low-dose group (MD, −0.10; 95% CI, −0.19 to −0.01). Our findings suggest that add-on tolvaptan therapy for heart failure improves fluid retention in the early therapy phase. However, this drug should be properly used to avoid the worsening of renal function, which may occur at high doses.