Targeting hyponatremia and hemodynamics in acute decompensated heart failure: is there a role for vasopressin antagonists?
Current treatment of acute decompensated heart failure (ADHF) has not reduced the significant morbidity or mortality associated with this disease, and has promoted drug development aimed at neurohormonal targets. Hypervolemic hyponatremia, which is linked to the nonosmotic release of arginine vasopressin, is associated with a poor prognosis in patients with heart failure (HF). Vasopressin acts on V(2) and V(1a) receptors to cause water retention and vasoconstriction, respectively. Clinical trials have demonstrated that vasopressin receptor antagonists (VRAs) are effective in treating hypervolemic hyponatremia in ADHF without a negative impact on renal function. The small hemodynamic benefit seen with VRA use appeared to result from V(2)-receptor antagonist-induced increase in urine output rather than from a vasodilatory drug effect. VRA use in ADHF trials was associated with minimal symptomatic improvement and no impact on morbidity or mortality. At present, clinical trial evidence does not support the routine use of VRAs in ADHF. Given the favorable renal profile of VRAs, studies on the possible benefit of VRAs in ADHF patients with renal insufficiency and diuretic resistance appear warranted.
Tufts University School of Medicine, Baystate Medical Center, S-4665, Cardiology, Springfield, MA 01199, USA.
Gregory
G
Valania
Manmeet
M
Singh
Mara T
MT
Slawsky
D000208:Acute Disease; D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001549:Benzamides / Q000494:pharmacology; D001552:Benzazepines / Q000494:pharmacology; D002986:Clinical Trials as Topic; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006439:Hemodynamics; D006801:Humans; D007010:Hyponatremia / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D011379:Prognosis; D011758:Pyrroles / Q000494:pharmacology; D000077602:Tolvaptan; D014661:Vasoconstriction / Q000187:drug effects; D014667:Vasopressins / Q000037:antagonists & inhibitors*; D001569:Benzodiazepines
D065092:Antidiuretic Hormone Receptor Antagonists; D001549:Benzamides; D001552:Benzazepines; D011758:Pyrroles; D000077602:Tolvaptan; D014667:Vasopressins; C106389:conivaptan; C409452:lixivaptan; D001569:Benzodiazepines