Acute hemodynamic effects of conivaptan, a dual V1A and V2 vasopressin receptor antagonist, in patients with advanced heart failure

James E. Udelson, William Smith, Grady H. Hendrix, Christopher A. Painchaud, Maha Ghazzi, Ignatius Thomas, Jalal K. Ghali, Paulina Selaru, Francoise Chanoine, Milton L. Pressler, Marvin A. Konstam

Research output: Contribution to journalArticle

309 Citations (Scopus)

Abstract

Background - Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V1A (vascular and myocardial effects) and V2 receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. Methods and Results - A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V1a/V2 vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6±0.7, -5.4±0.7, and -4.6±0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) and right atrial pressure (-2.0±0.4, -3.7±0.4, and -3.5±0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11±17, 68±17, 152±19, and 176±18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. Conclusions - In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.

Original languageEnglish (US)
Pages (from-to)2417-2423
Number of pages7
JournalCirculation
Volume104
Issue number20
DOIs
StatePublished - Nov 13 2001
Externally publishedYes

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Heart Failure
Hemodynamics
Placebos
Vasopressin Receptors
Vasopressins
Vascular Resistance
Heart Rate
Urine
Blood Pressure
Pulmonary Wedge Pressure
Atrial Pressure
Water-Electrolyte Balance
Arginine Vasopressin
Natural History
Intravenous Administration
Blood Vessels
Antidiuretic Hormone Receptor Antagonists
conivaptan
Kidney
Therapeutics

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Acute hemodynamic effects of conivaptan, a dual V1A and V2 vasopressin receptor antagonist, in patients with advanced heart failure. / Udelson, James E.; Smith, William; Hendrix, Grady H.; Painchaud, Christopher A.; Ghazzi, Maha; Thomas, Ignatius; Ghali, Jalal K.; Selaru, Paulina; Chanoine, Francoise; Pressler, Milton L.; Konstam, Marvin A.

In: Circulation, Vol. 104, No. 20, 13.11.2001, p. 2417-2423.

Research output: Contribution to journalArticle

Udelson, JE, Smith, W, Hendrix, GH, Painchaud, CA, Ghazzi, M, Thomas, I, Ghali, JK, Selaru, P, Chanoine, F, Pressler, ML & Konstam, MA 2001, 'Acute hemodynamic effects of conivaptan, a dual V1A and V2 vasopressin receptor antagonist, in patients with advanced heart failure', Circulation, vol. 104, no. 20, pp. 2417-2423. https://doi.org/10.1161/hc4501.099313
Udelson, James E. ; Smith, William ; Hendrix, Grady H. ; Painchaud, Christopher A. ; Ghazzi, Maha ; Thomas, Ignatius ; Ghali, Jalal K. ; Selaru, Paulina ; Chanoine, Francoise ; Pressler, Milton L. ; Konstam, Marvin A. / Acute hemodynamic effects of conivaptan, a dual V1A and V2 vasopressin receptor antagonist, in patients with advanced heart failure. In: Circulation. 2001 ; Vol. 104, No. 20. pp. 2417-2423.
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abstract = "Background - Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V1A (vascular and myocardial effects) and V2 receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. Methods and Results - A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V1a/V2 vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6±0.7, -5.4±0.7, and -4.6±0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) and right atrial pressure (-2.0±0.4, -3.7±0.4, and -3.5±0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11±17, 68±17, 152±19, and 176±18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. Conclusions - In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.",
author = "Udelson, {James E.} and William Smith and Hendrix, {Grady H.} and Painchaud, {Christopher A.} and Maha Ghazzi and Ignatius Thomas and Ghali, {Jalal K.} and Paulina Selaru and Francoise Chanoine and Pressler, {Milton L.} and Konstam, {Marvin A.}",
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T1 - Acute hemodynamic effects of conivaptan, a dual V1A and V2 vasopressin receptor antagonist, in patients with advanced heart failure

AU - Udelson, James E.

AU - Smith, William

AU - Hendrix, Grady H.

AU - Painchaud, Christopher A.

AU - Ghazzi, Maha

AU - Thomas, Ignatius

AU - Ghali, Jalal K.

AU - Selaru, Paulina

AU - Chanoine, Francoise

AU - Pressler, Milton L.

AU - Konstam, Marvin A.

PY - 2001/11/13

Y1 - 2001/11/13

N2 - Background - Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V1A (vascular and myocardial effects) and V2 receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. Methods and Results - A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V1a/V2 vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6±0.7, -5.4±0.7, and -4.6±0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) and right atrial pressure (-2.0±0.4, -3.7±0.4, and -3.5±0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11±17, 68±17, 152±19, and 176±18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. Conclusions - In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.

AB - Background - Arginine vasopressin may contribute to abnormalities in hemodynamics and fluid balance in heart failure through its actions on V1A (vascular and myocardial effects) and V2 receptors (renal effects). Inhibiting the action of vasopressin may be beneficial in patients with heart failure. Methods and Results - A total of 142 patients with symptomatic heart failure (New York Heart Association class III and IV) were randomized to double-blind, short-term treatment with conivaptan, a dual V1a/V2 vasopressin receptor antagonist, at a single intravenous dose (10, 20, or 40 mg) or placebo. Compared with placebo, conivaptan at 20 and 40 mg significantly reduced pulmonary capillary wedge pressure (-2.6±0.7, -5.4±0.7, and -4.6±0.7 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) and right atrial pressure (-2.0±0.4, -3.7±0.4, and -3.5±0.4 mm Hg for placebo and 20 and 40 mg groups, respectively; P<0.05) during the 3- to 6-hour interval after intravenous administration. Conivaptan significantly increased urine output in a dose-dependent manner (-11±17, 68±17, 152±19, and 176±18 mL/hour for placebo and 10, 20, and 40 mg groups, respectively; P<0.001) during the first 4 hours after the dose. Changes in cardiac index, systemic and pulmonary vascular resistance, blood pressure, and heart rate did not significantly differ from placebo. Conclusions - In patients with advanced heart failure, vasopressin receptor antagonism with conivaptan resulted in favorable changes in hemodynamics and urine output without affecting blood pressure or heart rate. These data suggest that vasopressin is functionally significant in advanced heart failure and that further investigations are warranted to examine the effects of conivaptan on symptom relief and natural history in such patients.

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