Nesiritide

Nesiritide is recombinant human B-type natriuretic peptide identical in sequence to the endogenous 32-amino acid cardiac hormone. It was developed as a therapeutic agent for acute decompensated heart failure, providing the hemodynamic and renal effects of BNP through exogenous administration.

The compound acts through natriuretic peptide receptor A (NPR-A), activating guanylyl cyclase and increasing intracellular cGMP in vascular smooth muscle and renal cells. This produces balanced venous and arterial vasodilation, reducing both preload and afterload, along with natriuresis and diuresis that help relieve fluid overload.

Nesiritide received FDA approval in 2001 for treatment of acute decompensated heart failure with dyspnea at rest or minimal exertion. It represented the first new intravenous therapy for acute heart failure in over a decade. However, subsequent studies raised questions about renal safety and mortality effects, leading to more cautious use.

The ASCEND-HF trial (2011) demonstrated nesiritide was not associated with increased mortality but also showed only modest symptomatic benefit. These findings led to reduced clinical utilization, though nesiritide remains available and continues to be studied for optimal patient selection and combination therapy approaches in acute heart failure management.