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Introduction: Hypervolemia and hyponatremia are common features in heart failure and have been associated with increased morbidity and mortality. Stimulation of arginine vasopressin (AVP) plays an important role in the development of both hypervolemia and hyponatremia. Lixivaptan is a selective vasopressin type 2 (V(2)) receptor antagonist that has been demonstrated to have the ability to induce aquaresis, the electrolyte sparing excretion of water, resulting in fluid removal as well as correction of hyponatremia., Areas Covered: This article describes the prevalence, pathophysiology and current treatment limitations of hyponatremia, highlights the importance of arginine vasopressin and the potential role of arginine vasopressin antagonists and reviews all available literature on lixivaptan, a selective V(2) receptor antagonist., Expert Opinion: The available experience of lixivaptan in heart failure, although limited, is encouraging. Its aquaretic effect provides the basis for its use to correct hypervolemia and hyponatremia in patients with heart failure, and the absence of neurhormonal stimulation provides positive signal for the exploration of its potential in improving outcomes.

Sex-related differences in clinical and laboratory characteristics, course and prognosis are well documented in patients with heart failure. However, most information regarding heart failure therapies has been obtained from studies conducted primarily in men. Reviewing the existing literature indicates that the recommendations regarding pharmacological and device therapies should apply similarly to men and women. One possible exception, however, is the possibility of more benefit derived from angiotensin receptor blockers in women, and from angiotensin converting enzyme inhibitors in men. Future clinical trials should be conducted either exclusively in women or have a larger representation of women to insure the adequate assessment of the potential benefit versus risk in women.