Vasopressin V2-receptor blockade with tolvaptan in patients with chronic heart failure: results from a double-blind, randomized trial.
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).


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.
Northwestern University Feinberg School of Medicine, 201 East Huron St, Galter 10-240, Chicago, Ill 60611, USA. m-gheorghiade@northwestern.edu
Mihai
M
Gheorghiade
Imran
I
Niazi
John
J
Ouyang
Frank
F
Czerwiec
Jun-ichi
J
Kambayashi
Manuela
M
Zampino
Cesare
C
Orlandi
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin / Q000097:blood; D001552:Benzazepines / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002908:Chronic Disease; D004232:Diuretics / Q000627:therapeutic use; D004311:Double-Blind Method; D004489:Edema, Cardiac / Q000188:drug therapy / Q000209:etiology; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D006333:Heart Failure / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007010:Hyponatremia / Q000150:complications / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012964:Sodium / Q000097:blood; D000077602:Tolvaptan; D016896:Treatment Outcome; D016482:Urinalysis; D014882:Water-Electrolyte Balance / Q000187:drug effects
D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D001127:Arginine Vasopressin; D000077602:Tolvaptan; D005665:Furosemide; D012964:Sodium