Vasopressin receptor antagonists

From pivotal trials to current practice

Ankur Kalra, Valmiki Maharaj, Steven R. Goldsmith

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Heart failure is a growing health and economic problem in America, and outcomes continue to remain dismal, particularly for those presenting with acute heart failure syndrome (AHFS). In theory, arginine vasopressin antagonists (VRAs) could be useful in both acute and chronic heart failure, depending on which vasopressin receptor is targeted. Most studies of VRAs in heart failure have focused on V2 receptor antagonism, and to a lesser extent on combined V1a/V2 antagonism, due to the availability of appropriate agents and the unmet need of improving outcomes in AHFS. These agents are particularly attractive as adjunctive or alterative agents in AHFS because of their ability to produce a substantial diuresis without some of the drawbacks intrinsic to loop diuretics. While VRAs have been shown to ameliorate signs and symptoms of congestion when added to standard care, the largest trial of these agents showed no improvement in long-term morbidity, mortality, or hospitalization rates when added to standard care. This article reviews the mechanism of action of VRAs, the relevant clinical trials data, and current recommendations for clinical use, and suggests future directions for study of these agents in patients with heart failure.

Original languageEnglish (US)
Pages (from-to)10-18
Number of pages9
JournalCurrent Heart Failure Reports
Volume11
Issue number1
DOIs
StatePublished - Mar 1 2014

Fingerprint

Heart Failure
Vasopressin Receptors
Sodium Potassium Chloride Symporter Inhibitors
Arginine Vasopressin
Diuresis
Proxy
Antidiuretic Hormone Receptor Antagonists
Signs and Symptoms
Hospitalization
Economics
Clinical Trials
Morbidity
Mortality
Health

Keywords

  • Antidiuretic hormone
  • Arginine vasopressin
  • Conivaptan
  • Tolvaptan

Cite this

Vasopressin receptor antagonists : From pivotal trials to current practice. / Kalra, Ankur; Maharaj, Valmiki; Goldsmith, Steven R.

In: Current Heart Failure Reports, Vol. 11, No. 1, 01.03.2014, p. 10-18.

Research output: Contribution to journalArticle

@article{8feb00899cac4234977958832c70cdeb,
title = "Vasopressin receptor antagonists: From pivotal trials to current practice",
abstract = "Heart failure is a growing health and economic problem in America, and outcomes continue to remain dismal, particularly for those presenting with acute heart failure syndrome (AHFS). In theory, arginine vasopressin antagonists (VRAs) could be useful in both acute and chronic heart failure, depending on which vasopressin receptor is targeted. Most studies of VRAs in heart failure have focused on V2 receptor antagonism, and to a lesser extent on combined V1a/V2 antagonism, due to the availability of appropriate agents and the unmet need of improving outcomes in AHFS. These agents are particularly attractive as adjunctive or alterative agents in AHFS because of their ability to produce a substantial diuresis without some of the drawbacks intrinsic to loop diuretics. While VRAs have been shown to ameliorate signs and symptoms of congestion when added to standard care, the largest trial of these agents showed no improvement in long-term morbidity, mortality, or hospitalization rates when added to standard care. This article reviews the mechanism of action of VRAs, the relevant clinical trials data, and current recommendations for clinical use, and suggests future directions for study of these agents in patients with heart failure.",
keywords = "Antidiuretic hormone, Arginine vasopressin, Conivaptan, Tolvaptan",
author = "Ankur Kalra and Valmiki Maharaj and Goldsmith, {Steven R.}",
year = "2014",
month = "3",
day = "1",
doi = "10.1007/s11897-013-0175-3",
language = "English (US)",
volume = "11",
pages = "10--18",
journal = "Molecular Pharmaceutics",
issn = "1543-8384",
publisher = "American Chemical Society",
number = "1",

}

TY - JOUR

T1 - Vasopressin receptor antagonists

T2 - From pivotal trials to current practice

AU - Kalra, Ankur

AU - Maharaj, Valmiki

AU - Goldsmith, Steven R.

PY - 2014/3/1

Y1 - 2014/3/1

N2 - Heart failure is a growing health and economic problem in America, and outcomes continue to remain dismal, particularly for those presenting with acute heart failure syndrome (AHFS). In theory, arginine vasopressin antagonists (VRAs) could be useful in both acute and chronic heart failure, depending on which vasopressin receptor is targeted. Most studies of VRAs in heart failure have focused on V2 receptor antagonism, and to a lesser extent on combined V1a/V2 antagonism, due to the availability of appropriate agents and the unmet need of improving outcomes in AHFS. These agents are particularly attractive as adjunctive or alterative agents in AHFS because of their ability to produce a substantial diuresis without some of the drawbacks intrinsic to loop diuretics. While VRAs have been shown to ameliorate signs and symptoms of congestion when added to standard care, the largest trial of these agents showed no improvement in long-term morbidity, mortality, or hospitalization rates when added to standard care. This article reviews the mechanism of action of VRAs, the relevant clinical trials data, and current recommendations for clinical use, and suggests future directions for study of these agents in patients with heart failure.

AB - Heart failure is a growing health and economic problem in America, and outcomes continue to remain dismal, particularly for those presenting with acute heart failure syndrome (AHFS). In theory, arginine vasopressin antagonists (VRAs) could be useful in both acute and chronic heart failure, depending on which vasopressin receptor is targeted. Most studies of VRAs in heart failure have focused on V2 receptor antagonism, and to a lesser extent on combined V1a/V2 antagonism, due to the availability of appropriate agents and the unmet need of improving outcomes in AHFS. These agents are particularly attractive as adjunctive or alterative agents in AHFS because of their ability to produce a substantial diuresis without some of the drawbacks intrinsic to loop diuretics. While VRAs have been shown to ameliorate signs and symptoms of congestion when added to standard care, the largest trial of these agents showed no improvement in long-term morbidity, mortality, or hospitalization rates when added to standard care. This article reviews the mechanism of action of VRAs, the relevant clinical trials data, and current recommendations for clinical use, and suggests future directions for study of these agents in patients with heart failure.

KW - Antidiuretic hormone

KW - Arginine vasopressin

KW - Conivaptan

KW - Tolvaptan

UR - http://www.scopus.com/inward/record.url?scp=84896734969&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84896734969&partnerID=8YFLogxK

U2 - 10.1007/s11897-013-0175-3

DO - 10.1007/s11897-013-0175-3

M3 - Article

VL - 11

SP - 10

EP - 18

JO - Molecular Pharmaceutics

JF - Molecular Pharmaceutics

SN - 1543-8384

IS - 1

ER -