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
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. 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. 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. 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.