Benefit-risk assessment of nesiritide in the treatment of acute decompensated heart failure.

Nesiritide is a recombinant form of human B-type natriuretic peptide, a naturally occurring endogenous hormone released by cardiac ventricles in response to an increase in ventricular wall stress. Its use in the treatment of acute decompensated heart failure (ADHF) has been evaluated in a series of randomised controlled clinical trials. It is currently approved in the US for the treatment of ADHF. Nesiritide induces a balanced vasodilation and an indirect increase in cardiac output, but has no actual inotropic effects and exerts a neutral effect on heart rate. In addition, it inhibits adverse neurohormonal activation and, in some individuals, promotes natriuresis and diuresis. In adults with ADHF, nesiritide reduces pulmonary capillary wedge pressure, right atrial pressure and systemic vascular resistance; decreases symptoms of heart failure; and enhances global clinical status. Important questions regarding the risks of nesiritide therapy have recently been raised, and resolution of the safety of nesiritide is a process that remains in evolution. The most frequently reported adverse effect is dose-related hypotension. In addition, nesiritide may cause an acute increase in serum creatinine concentration. This increase seems to be a haemodynamic response to a combination of volume depletion, vasodilation and neurohormonal inhibition. Nesiritide-induced changes in renal function have not been definitively shown to negatively affect mortality. The effect of nesiritide on all-cause mortality is currently unresolved. Recent meta-analyses of existing databases have raised concerns regarding adverse effects of the drug on 30-day mortality. However, reviews of large, observational, registry databases do not suggest an adverse inpatient mortality effect compared with other vasodilator therapies. Further resolution of the mortality question awaits completion of pending randomised controlled clinical trials. When used for approved indications and according to recommended dosage and administration regimens, nesiritide represents a reasonable treatment adjunct for ADHF.