Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Late Breaking Cohort Studies (JCS 2014)
Efficacy and Safety of Tolvaptan in Heart Failure Patients With Volume Overload
– An Interim Result of Post-Marketing Surveillance in Japan –
Koichiro KinugawaNaoki SatoTakayuki InomataToshiyuki ShimakawaNoriaki IwatakeKazuki Mizuguchi
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Supplementary material

2014 Volume 78 Issue 4 Pages 844-852


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.  (Circ J 2014; 78: 844–852)

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