Recombinant BNP · acute heart failure
Nesiritide is human B-type natriuretic peptide (BNP), one of the heart's own hormones, produced with recombinant DNA technology. Branded Natrecor, it was an intravenous hospital drug for people with acutely decompensated heart failure and shortness of breath. FDA records now list it as discontinued.
When the heart's chambers are overfilled, ventricular muscle releases BNP. BNP binds a particulate guanylate cyclase receptor on the smooth muscle and lining cells of blood vessels, raising cyclic GMP inside them. Cyclic GMP relaxes the muscle, widening both veins and arteries. That lowers the filling pressure inside the heart, measured as pulmonary capillary wedge pressure, which can ease lung congestion and breathlessness.
In animal studies, nesiritide did not change the heart's pumping strength or its electrical conduction. Its blood-pressure effect outlasts its short half-life in the blood, so low blood pressure, when it happens, can take an hour or more to resolve and lasted longer than with nitroglycerin in trials.
In the VMAC trial of 489 hospitalized patients, nesiritide lowered wedge pressure more than nitroglycerin or placebo at three hours and improved breathlessness versus placebo, though not versus nitroglycerin2. A 2005 pooled analysis of three trials raised concern about a possible rise in 30-day deaths (7.2% versus 4.0%, just short of statistical significance)3. The large ASCEND-HF trial in 7,141 patients then found no difference in death or heart-failure rehospitalization at 30 days (9.4% versus 10.1%) and no significant worsening of kidney function, but the improvement in breathlessness was small and missed the prespecified threshold, and low blood pressure was more common4. The authors concluded it could not be recommended for routine use in acute heart failure4.
FDA-approved in 2001 as Natrecor (Scios) for acutely decompensated heart failure with breathlessness at rest or with minimal activity. FDA records now list it as discontinued, noting a determination that it was not withdrawn for reasons of effectiveness or harm.
Per the label, the most common effects were low blood pressure, headache, nausea and back pain1. Low blood pressure is the main limiting risk and lasted longer than with nitroglycerin when it occurred; the drug is contraindicated in cardiogenic shock and with persistently low systolic pressure. The label also warns of rising serum creatinine (worsening kidney function) and serious allergic reactions, especially in people sensitive to recombinant peptides.
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