College of American Pathologists
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Treating with nesiritide

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February 2002
William Check, PhD

Understanding the physiology of B-type natriuretic peptide in heart failure led to the therapeutic agent nesiritide (Natrecor, Scios Inc.)—BNP produced by recombinant technology. Nesiritide is indicated to treat patients with acute heart failure—dyspnea at rest or with minimal activity.

When heart function weakens, the hormones of the renin-angiotensin-aldosterone (RAA) system increase to preserve blood flow to the kidneys, brain, and other vital organs, explains Chester Falterman, MD, of the Heart Clinic of Louisiana in New Orleans. This benefit comes at the expense of constricting arteries and increased salt and water retention, with the effect being more stress placed on a failing heart and resulting in pulmonary edema and congestive heart failure.

In response, the heart secretes BNP, which causes vasodilatation and decreased sympathetic outflow, promotes salt and water wasting, and counteracts the RAA system. Unfortunately, the heart cannot make enough BNP to completely counter these detrimental counter-regulatory hormones, and fluid buildup and congestive heart failure result. "This is why it’s necessary to give nesiritide in super-therapeutic doses,"Dr. Falterman says. (Although heart failure patients are treated with ACE inhibitors, antagonism of the RAA system is incomplete.)

In clinical trials, nesiritide was evaluated in outpatients presenting to the ED with acute decompensated heart failure and in hospitalized patients with New York Heart Association class IV heart failure. Nesiritide acted faster than nitroglycerin, with an onset of action of 15 minutes. And a fixed dose of nesiritide (bolus plus infusion) had a sustained effect over 24 hours, while nitroglycerin needed to be uptitrated. Dr. Falterman says the ability to use a standard dose of nesiritide is a big advantage: "Uptitration [of nitroglycerin] is often not done in community hospitals."

A trial is underway to test whether nesiritide can reverse acute heart failure rapidly enough so that some patients bypass intensive care and can be sent to stepdown or telemetry units, yielding cost savings. "I have seen that situation frequently in my practice," Dr. Falterman says. Another endpoint is a reduction in the readmission rate for heart failure—currently 20 to 30 percent at three to six months.