Hyponatremia and Congestive Heart Failure: A Marker of Increased Mortality and a Target for Therapy

Heart failure is one of the most common chronic medical conditions in the developed world. It is characterized by neurohormonal activation of multiple systems that can lead to clinical deterioration and significant morbidity and mortality. In this regard, hyponatremia is due to inappropriate and continued vasopressin activity despite hypoosmolality and volume overload. Hyponatremia is also due to diuretic use in an attempt to manage volume overload. When hyponatremia occurs, it is a marker of heart failure severity and identifies patients with increased mortality. The recent introduction of specific vasopressin-receptor antagonists offers a targeted pharmacological approach to these pathophysiological derangements. Thus far, clinical trials with vasopressin-receptor antagonists have demonstrated an increase in free-water excretion, improvement in serum sodium, modest improvements in dyspnea but no improvement in mortality. Continued clinical trials with these agents are needed to determine their specific role in the treatment of both chronic and decompensated heart failure.

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Conivaptan: New treatment for hyponatremia

American Journal of Health-System Pharmacy ◽

10.2146/ajhp060383 ◽

2007 ◽

Vol 64 (13) ◽

pp. 1385-1395 ◽

Cited By ~ 10

Author(s):

Kimberly A. Walter

Keyword(s):

Heart Failure ◽

Acute Decompensated Heart Failure ◽

Free Water ◽

Decompensated Heart Failure ◽

The United States ◽

Multicenter Studies ◽

Double Blind ◽

Water Excretion ◽

Safety Issues ◽

Dosing Regimens

Abstract Purpose. The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, adverse effects and toxicities, drug interactions, dosage and administration, and safety issues related to the use of conivaptan are discussed. Summary. Conivaptan hydrochloride is a nonpeptide, V1A and V2 vasopressin-receptor antagonist. It is available as an i.v. formulation in 4-mL ampules containing 20 mg of conivaptan hydrochloride. The drug is active both orally and i.v. Conivaptan injection is approved for the treatment of euvolemic hyponatremia in hospitalized patients. Three double-blind, placebo-controlled, randomized, multicenter studies have been conducted in the United States and internationally. The studies used various dosing regimens for conivaptan but maintained the same efficacy endpoints. Each study showed conivaptan to be effective in increasing serum sodium and in water clearance. Conivaptan is being evaluated in the treatment of acute decompensated heart failure and chronic heart failure, but the safety of this drug has not been fully established. The drug has been generally well tolerated in clinical trials with both oral and i.v. administration. The approved dosing regimen consists of a 20-mg i.v. loading dose administered over 30 minutes, followed by a continuous infusion of 20 mg administered over 24 hours. Clinical studies evaluating conivaptan have been short term; longer-term effects of hemodynamic parameters are unknown. Conclusion. Conivaptan, the first vasopressin antagonist approved for the treatment of euvolemic hyponatremia, has a unique mechanism of action that results in free-water excretion and offers a new option for the treatment of resistant hyponatremia in the acute setting when patients have not responded to standard management.

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