title: Response Prediction and Influence of Tolvaptan in Chronic Heart Failure Patients Considering the Interaction of the Renin-Angiotensin-Aldosterone System and Arginine Vasopressin.
abstract: The renin-angiotensin-aldosterone system (RAAS) and arginine vasopressin (AVP) regulate body fluids. Although conventional diuretics have been used for treating heart failure, they activate RAAS and exacerbate renal function. Tolvaptan, a newly developed vasopressin-2 receptor antagonist, elicits aquaresis and improves volume overload in heart failure patients, however, the predictors of tolvaptan effectiveness and the influence on the RAAS and renal function according to tolvaptan therapy are not established. We evaluated 26 chronic heart failure patients receiving therapy with 15 mg/day tolvaptan and examined their laboratory and urinary data before and after tolvaptan therapy. A response to tolvaptan was defined as a body weight decrease by more than 2 kg in a week and a urine volume increase by 500 mL/ day compared with that before tolvaptan administration. Body weight, urine volume, and brain natriuretic peptide levels significantly improved (P < 0.05), without any worsening of renal function represented by serum creatinine, sodium, and potassium. Moreover, no significant changes were observed in the plasma renin activity and plasma aldosterone concentration (PAC). In the responder group, urine osmolality before tolvaptan administration was significantly higher (P < 0.05) but declined significantly after tolvaptan administration (P < 0.05). The AVP/PAC ratio before administration was positively correlated with the efficacy of tolvaptan. Tolvaptan treatment could prevent RAAS activation in chronic heart failure patients. Moreover, monitoring the AVP/PAC ratio may be useful in predicting the tolvaptan response.
authors.affiliation: Department of Cardiovascular Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School.
authors.forename: Muneyuki
authors.initials: M
authors.lastname: Kadota
authors.forename: Takayuki
authors.initials: T
authors.lastname: Ise
authors.forename: Shusuke
authors.initials: S
authors.lastname: Yagi
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwase
authors.forename: Masashi
authors.initials: M
authors.lastname: Akaike
authors.forename: Rie
authors.initials: R
authors.lastname: Ueno
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Kawabata
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hara
authors.forename: Kozue
authors.initials: K
authors.lastname: Ogasawara
authors.forename: Mika
authors.initials: M
authors.lastname: Bando
authors.forename: Sachiko
authors.initials: S
authors.lastname: Bando
authors.forename: Tomomi
authors.initials: T
authors.lastname: Matsuura
authors.forename: Koji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Hirotsugu
authors.initials: H
authors.lastname: Yamada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Soeki
authors.forename: Tetsuzo
authors.initials: T
authors.lastname: Wakatsuki
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D065092:Antidiuretic Hormone Receptor Antagonists / Q000627:therapeutic use*; D001127:Arginine Vasopressin / Q000187:drug effects*; D001552:Benzazepines / Q000627:therapeutic use*; D015992:Body Mass Index; D005260:Female; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012084:Renin-Angiotensin System / Q000187:drug effects*; D000077602:Tolvaptan; D016896:Treatment Outcome
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D001127:Arginine Vasopressin; D000077602:Tolvaptan