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(Circulation. 2003;107:2690.)
© 2003 American Heart Association, Inc.

Clinical Investigation and Reports

Vasopressin V₂-Receptor Blockade With Tolvaptan in Patients With Chronic Heart Failure

Results From a Double-Blind, Randomized Trial

Mihai Gheorghiade, MD; Imran Niazi, MD; John Ouyang, MD; Frank Czerwiec, MD; Jun-ichi Kambayashi, MD; Manuela Zampino, MD; Cesare Orlandi, MD, for the Tolvaptan Investigators

From Northwestern University Feinberg School of Medicine, Chicago, Ill (M.G., M.Z.); Wisconsin Center for Clinical Research, Elkhorn, Wis (I.N.); and Otsuka Maryland Research Institute, Rockville, Md (J.O., F.C., J.K., C.O.).

Correspondence to Mihai Gheorghiade, MD, Northwestern University Feinberg School of Medicine, 201 East Huron St, Galter 10–240, Chicago, IL 60611. E-mail m-gheorghiade{at}northwestern.edu

Background— In this study, we evaluated the effects of tolvaptan (OPC-41061), a novel, oral, nonpeptide vasopressin V₂-receptor antagonist in patients with chronic heart failure (CHF).

Methods and Results— This was a double-blind study investigating the effects of three doses of tolvaptan and placebo in patients with CHF. After a run-in period, 254 patients were randomly assigned to placebo (n=63) or tolvaptan [30 mg (n=64), 45 mg (n=64), or 60 mg (n=63)] once daily for 25 days. Patients were not fluid-restricted and were maintained on stable doses of furosemide. At day 1, when compared with baseline, a decrease in body weight of -0.79±0.99, -0.96±0.93, and -0.84±0.02 kg was observed in the 30-, 45-, and 60-mg tolvaptan groups, respectively, and a body weight increase of +0.32±0.46 kg in the placebo group (P<0.001 for all treatment groups versus placebo). Although the initial decrease in body weight was maintained during the study, no further reduction was observed beyond the first day. An increase in urine volume was observed with tolvaptan when compared with placebo (3.9±0.6, 4.2±0.9, 4.6±0.4, and 2.3±0.2 L/24 hours at day 1 for 30-, 45-, and 60-mg tolvaptan groups, and placebo, respectively; P<0.001). A decrease in edema and a normalization of serum sodium in patients with hyponatremia were observed in the tolvaptan group but not in the placebo group. No significant changes in heart rate, blood pressure, serum potassium, or renal function were observed.

Conclusions— In patients with CHF, tolvaptan was well tolerated; it reduced body weight and edema and normalized serum sodium in the hyponatremic patients.

Key Words: heart failure • trials • hormones • edema

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