title: Efficacy and safety of tolvaptan in heart failure patients with volume overload.
abstract: 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.
  
  
  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.
authors.affiliation: Department of Therapeutic Strategy for Heart Failure, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. kinugawa-tky@unin.ac.jp
authors.forename: Koichiro
authors.initials: K
authors.lastname: Kinugawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Sato
authors.forename: Takayuki
authors.initials: T
authors.lastname: Inomata
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Shimakawa
authors.forename: Noriaki
authors.initials: N
authors.lastname: Iwatake
authors.forename: Kazuki
authors.initials: K
authors.lastname: Mizuguchi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001552:Benzazepines / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D011358:Product Surveillance, Postmarketing; D011446:Prospective Studies; D000077602:Tolvaptan
chemical_list: D001552:Benzazepines; D000077602:Tolvaptan