Vasopressin Receptor Antagonists (Vaptans) in Heart Failure

Arginine vasopressin (a peptide neuroendocrine hormone) levels are elevated in patients with HF. Acting through 3 receptor subtypes, it can cause vasoconstriction and cardiac remodelling (receptors V1a), adrenocorticotropic hormone release (receptors V1b) and water reabsorption (receptors V2), thereby increasing preload and afterload. Vasopressin-receptor antagonists (vaptans), induce hypotonic diuresis and have been proposed as a treatment option for hyponatraemia, a known complication of HF. Three vaptans have been so tested; tolvaptan, conivaptan and lixivaptan, and  two (tolvaptan and conivaptan) have been approved for clinical use in hyponatraemia (in the USA). The EVEREST trial studied tolvaptan in over 4100 patients hospitalized with an exacerbation of chronic HF with reduced LVEF. No effect was seen on long-term mortality or HF-related morbidity, but there was greater weight loss and better dyspnoea and oedema relief over the short-term.  Similar results were seen in the AQUAMARINE study. The 2016 European HF guidelines, therefore gave the limited recommendation: “Tolvaptan may be used to treat patients with volume overload and resistant hyponatraemia”. Despite targeting  an attractive  therapeutic target,  vasopressin receptor antagonists (vaptans) have to date played only a minor role in our management of HF.