Effects of tolvaptan on volume overload in Japanese patients with heart failure: Results of a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study

Purpose: Tolvaptan may reduce the signs of volume overload in heart failure (HF) patients who experience volume overload despite using conventional diuretics. In this study, we evaluated the dose-response effects of tolvaptan on weight loss, urine volume and electrolyte excretion in furosemide-treated Japanese HF patients exhibiting volume overload. Methods: In the study, 117 HF patients with volume overload on stable doses of furosemide (≥40 mg/day) were treated with tolvaptan (15, 30 or 45 mg) or placebo once-daily for 7 days. Results: The decrease in body weight from baseline to the day after the final dose with 15, 30 or 45 mg tolvaptan (-1.62±1.55, -1.35±1.54 and -1.85±1.10 kg, respectively), was significantly greater compared with that in the placebo group (-0.53±0.96 kg) (p<0.05). However, the decrease in body weight with tolvaptan was not significantly dose-dependent. Signs of volume overload improved at all doses of tolvaptan. Tolvaptan elicited a dose-dependent increase in urine volume and a decrease in urine osmolality, but did not affect urinary sodium or potassium excretion. Adverse reactions associated with diuresis were most frequently observed at the higher doses of tolvaptan. Conclusions: Once-daily tolvaptan (15, 30 or 45 mg) was effective and tolerable as an add-on treatment to furosemide therapy in Japanese HF patients with volume overload. © 2011 Springer Science+Business Media, LLC.