Nesiritide
/ Recombinant 32-residue B-type natriuretic peptide (BNP-32); NPR-A receptor agonistALIAS · Natrecor (trade) · Recombinant BNP · BNP · B-type natriuretic peptide
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Tier 1 by regulatory status; clinical use has substantially declined. FDA approval 2001 for acutely decompensated heart failure based on the VMAC pivotal trial (NEJM 2002). The ASCEND-HF Phase 4 trial (O'Connor and colleagues, NEJM 2011) randomised approximately 7,141 participants and failed to demonstrate mortality, rehospitalisation, or robust dyspnea benefit, leading to substantial decline in clinical use despite retained approval.
Nesiritide is recombinant human B-type natriuretic peptide (BNP-32), sequence-identical to the endogenous peptide secreted by ventricular cardiomyocytes in response to volume and pressure overload. BNP binds the natriuretic peptide receptor A (NPR-A), a membrane guanylyl cyclase, raising intracellular cGMP and producing vasodilation (arterial and venous), natriuresis, diuresis, and suppression of the renin-angiotensin-aldosterone and sympathetic nervous systems. The acute haemodynamic profile in decompensated heart failure is reduced pulmonary capillary wedge pressure and systemic vascular resistance.
Tier 1 by trial completeness. The VMAC trial (VMAC Investigators, NEJM 2002) randomised approximately 489 participants with acute decompensated heart failure to nesiritide, nitroglycerin, or placebo, reporting greater pulmonary capillary wedge pressure reduction and dyspnea improvement with nesiritide versus placebo. Subsequent meta-analyses raised concerns about renal and mortality outcomes. The ASCEND-HF Phase 4 trial (O'Connor and colleagues, NEJM 2011) was designed to resolve these signals and randomised approximately 7,141 acutely decompensated heart failure participants; nesiritide produced no mortality benefit, no significant rehospitalisation reduction, and only marginal dyspnea improvement, with a numerical excess of hypotension. The ASCEND-HF result effectively ended the role of nesiritide in routine acute heart failure care.
Hypotension is the dominant adverse event, present in both VMAC and ASCEND-HF and intrinsic to the vasodilator pharmacology. Renal function decline raised regulatory and clinical concern in the post-VMAC era; ASCEND-HF did not demonstrate a clinically significant worsening renal function signal but did not show benefit either. Rare hypersensitivity reactions and headache have been reported.
Regulatory status
- FDA status:
- FDA-approved
- Compounding:
- Not eligible for compounding (approved, not in shortage)
Nesiritide is the textbook example of a positive surrogate-endpoint pivotal trial (VMAC: dyspnea, haemodynamics) that did not predict clinical-outcome benefit at scale (ASCEND-HF: mortality, rehospitalisation). The drug remains FDA-approved but is rarely used in current US heart failure practice; guidelines do not recommend it for routine acute decompensated heart failure care. Generic recombinant BNP availability is limited because demand collapsed.