EVEREST study: Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan

Abstract

Acute heart failure syndromes are a common cause of emergency department visits and hospitalization in North America and Europe. Although in-hospital mortality is relatively low, the postdischarge mortality and rehospitalization rates can be as high as 10–15 and 30%, respectively, within 60–90 days following discharge. It appears that the main reason for admission and readmission for heart failure is related to congestion manifested by dyspnea, jugular venous distension and edema. Often, congestion is associated with dilutional hyponatremia that is difficult to treat. Hyponatremia is an important predictor of increased mortality and the available therapies to treat congestion and/or hyponatremia are often ineffective and/or unsafe. Accordingly, there is an unmet need to develop a new agent that effectively relieves congestion due to high filling pressure without worsening renal function and improving or normalizing serum sodium in hyponatremic patients. This paper provides an overview of a new compound, tolvaptan, an oral selective V₂-vasopressin antagonist in light of the recently published Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial. The biochemical and pharmacological properties are discussed in conjunction with its clinical efficacy and safety, exploring the potential role of tolvaptan in the management of acute heart failure syndromes presenting with or without hyponatremia.

Keywords::

• acute heart failure syndrome
• fluid overload
• hyponatremia
• tolvaptan
• vasopressin antagonist

Financial & competing interests disclosure

Mihai Gheorghiade has received research grants from the US NIH, Merck, Otsuka, Scios Inc. and Sigma Tau; honoraria from Debbio Pharm, Errekappa Terapeutici, GlaxoSmithKline, Johnson and Johnson, Medtronic, Protein Design Labs, and Solvay; and acted as a consultant for Abbott, AstraZeneca, GlaxoSmithKline, Medtronic, Otsuke, Protein Design Labs, Scios Inc. and Sigma Tau. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.