Commentary: The Role of Nesiritide

January 2011

0111 Commentary BreslerThe majority of patients who present to the emergency department in acute pulmonary edema are markedly improved within 1 hour. As physicians whose specialty is largely based on rapid, lifesaving therapy, one of the most gratifying experiences we can have is the conversion of a patient gasping for breath and about to die, into one who is now comfortable and able to converse with us and with loved ones.

Unfortunately, the long-term prognosis for decompensated heart failure is not very good. These patients have high rates of return to the ED, admission to the hospital, and ultimately death.

And of course, there are those who do not respond to our ED treatment in the first place.

Therefore, when nesiritide was introduced approximately a decade ago, it offered hope for this very serious, and often ultimately fatal, disorder. The pathophysiologic basis of its action was unique compared with those of older therapeutic agents, and it was thought that nesiritide might be a major addition to our treatment modalities (J. Card. Fail. 1998;4:37-44; J. Am. Coll. Cardiol. 1999;34:155-62; JAMA 2002;287:1531-40).

However, the evidence for its clinical efficacy was not considered robust by many authorities. And a few years after its introduction, data were published indicating that nesiritide may have a deleterious effect on both renal function (Circulation 2005;111:1487-91) and mortality (JAMA 2005;293:1900-5).

This was particularly curious, given that one of nesiritide's theoretical advantages was to increase renal blood flow.

The studies cited in "Trial: Nesiritide Shown Safe for Acute Heart Failure" (see p. 1 of this issue) were designed to finally answer the questions of whether the drug is effective and whether it is harmful.

The results are mixed. The deleterious effect on renal function was not confirmed. Apparently, nesiritide is relatively safe. It can lower blood pressure, which has to be carefully monitored. But the drug does not harm the kidneys.

Unfortunately, nesiritide does not appear to be very effective. While some patients do benefit significantly, the proportion of those who do so is rather small, and identification of that subgroup is not apparent at this time.

So what can we conclude about nesiritide's role in emergency medicine? Only that it's worth a try when all else fails. Most patients who do not respond quickly to initial ED treatment will benefit from additional intravenous nitroglycerin.

But if that fails, and the blood pressure is carefully monitored, nesiritide may be considered.

A therapeutic deus ex machina for acute decompensated heart failure, alas, lies in the future.

Dr. Bresler is clinical professor, surgery, division of emergency medicine, Stanford University School of Medicine, Palo Alto, Calif.; and director, department of emergency medicine, Mills-Peninsula Health System, Burlingame, Calif. 

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