title: A multicenter, randomized, double-blind, placebo-controlled study of tolvaptan monotherapy compared to furosemide and the combination of tolvaptan and furosemide in patients with heart failure and systolic dysfunction.
abstract: BACKGROUND
  Increased vasopressin levels may be present in patient with chronic heart failure (HF) and contribute to pathophysiology through effects on the vasopressin V2 receptor. The presence of background diuretic therapy may confound evaluations of vasopressin receptor antagonists (VRA).
  
  
  RESULTS
  Eligible patients had HF (New York Heart Association Class II-III), systolic dysfunction (left ventricular ejection fraction ≤0.40) and signs of congestion (eg, edema, rales). At screening, patients were removed from baseline diuretic therapy and placed on a low-sodium diet (2 g/day). After a 2-day run-in period, 83 patients were randomized to placebo (n = 21), monotherapy with the vasopressin V2 receptor antagonist tolvaptan (TLV) 30 mg (n = 20), monotherapy with furosemide 80 mg (FURO, n = 22) or both TLV 30 mg and FURO 80 mg (n = 20) once daily for 7 days. Patients were on standard background therapy and not fluid-restricted throughout the study. A decrease in body weight of -1.37 ± 1.61, -0.54 ± 1.59, and -1.13 ± 1.49 kg was observed versus baseline for TLV, FURO, and TLV+FURO, respectively, at day 8. At the same point, the placebo group showed a body weight increase of +0.72 ± 2.42 kg versus baseline (P = .0006 for TLV versus placebo). Increases in urine volume from baseline were greater with TLV alone (2646 ± 1503 mL/24 hours) than with FURO (894 ± 853 mL/24 hours, P < .001), or PLC (423 ± 786 mL/24 hours, P < .001), and similar to TLV+FURO (2585 ± 2119 mL/24 hours). An increase in serum sodium within the normal range was also observed in TLV-treated patients (P < .02 versus placebo; P < .01 versus FURO). No changes in serum potassium, other laboratory values, or blood pressure were observed. TLV therapy was well tolerated.
  
  
  CONCLUSIONS
  In patients with HF and signs of volume overload, TLV monotherapy without concomitant loop diuretic therapy reduced body weight when compared to placebo without adverse changes in serum electrolytes, during a sodium restricted diet while on background medications including angiotensin-converting enzyme inhibitors and β-blockers.
authors: Division of Cardiology and the CardioVascular Center, Tufts Medical Center, Boston, MA 02111, USA. JUdelson@tuftsmedicalcenter.org
authors: James E
authors: JE
authors: Udelson
authors: Martin
authors: M
authors: Bilsker
authors: Paul J
authors: PJ
authors: Hauptman
authors: Rafael
authors: R
authors: Sequeira
authors: Ignatius
authors: I
authors: Thomas
authors: Terrence
authors: T
authors: O'Brien
authors: Christopher
authors: C
authors: Zimmer
authors: Cesare
authors: C
authors: Orlandi
authors: Marvin A
authors: MA
authors: Konstam
mesh_terms: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D004232:Diuretics / Q000627:therapeutic use*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D005665:Furosemide / Q000627:therapeutic use*; D054143:Heart Failure, Systolic / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013223:Statistics as Topic; D013318:Stroke Volume; D000077602:Tolvaptan; D014667:Vasopressins / Q000187:drug effects; D016277:Ventricular Function, Left
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D014667:Vasopressins; D000077602:Tolvaptan; D005665:Furosemide