Efficacy and safety of tolvaptan in heart failure patients with volume overload.

BACKGROUND  Loop diuretics are commonly used in heart failure (HF) patients, but they are sometimes associated with insufficient response as well as adverse events. In such diuretics-resistant cases, tolvaptan, a vasopressin type 2 receptor antagonist, shows the improvement of volume overload without electrolyte imbalance. Tolvaptan was launched in Japan in 2010, and a post-marketing surveillance has been performed to evaluate the safety and efficacy of tolvaptan in real-world clinical settings. METHODS AND RESULTS  HF patients with insufficient response to loop diuretics were enrolled: 1,053 to evaluate for efficacy and 1,057 patients for the safety assessment. Decreases in body weight from baseline were 1.0±1.6kg at day 2 and increases in urine volume were 631±1,179ml at day 1 (both P<0.0001 vs. baseline). Congestive symptoms were significantly improved within 14 days. Adverse drug reactions (ADR) were observed in 18.7%, with thirst being the most frequent ADR (10%). Hypernatremia was a complication in 40 patients (3.8%). Predictive factors for the occurrence of hypernatremia were the starting dosage of tolvaptan (15mg/day), baseline serum sodium level (≥142mEq/L) and serum potassium level (<3.8mEq/L) at baseline. CONCLUSIONS  In the real-world clinical setting, tolvaptan demonstrated aquaretic efficacy in HF patients with diuretic-resistant volume overload. We recommend a lower dose of tolvaptan in Japanese patients with normonatremia and hypokalemia to prevent hypernatremia.