Vasopressin-receptor antagonists in heart failure.

PURPOSE: The role of arginine vasopressin in heart failure and the use of vasopressin receptor antagonists in the treatment of heart failure are reviewed.
SUMMARY: Arginine vasopressin (AVP) functions in the regulation of plasma osmolarity and blood pressure. In heart failure, AVP worsens heart failure by causing vasoconstriction of arteries and veins, potentially contributing to remodeling of the left ventricle and causing fluid retention and worsening of hyponatremia. Two V(2)-receptor antagonists, tolvaptan and lixivaptan, and one combined V(1a)- and V(2)-receptor antagonist, conivaptan, have shown promise for use in patients with heart failure. All three agents have been shown to increase free water excretion and increase serum sodium levels while maintaining serum potassium levels. They have not been shown to decrease renal function or the glomerular filtration rate and are well tolerated, with thirst being the major adverse effect during clinical trials. Because of their effects on sodium, vasopressin antagonists need to be carefully monitored to ensure that serum sodium levels do not increase too quickly and put the patient at risk for overcorrection or osmotic demyelination syndrome. In addition, patients need to be monitored for signs of dehydration secondary to increased urine excretion. To date, studies have not consistently shown improvements in patient symptoms or weight reduction. However, early data suggest that at least one agent, tolvaptan, does not alter mortality.
CONCLUSION: Based on data from available clinical trials, vasopressin antagonists may offer a new treatment option for patients with congestive heart failure. However, these agents do not currently appear to delay the progression of heart failure or decrease mortality.