Treating with nesiritide
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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
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.