STEPS

New Drug Reviews

Nesiritide (Natrecor) for Acute Decompensated Heart Failure

Mark Shatsky, D.O., Oregon Health and Science University, Portland, Oregon

Synopsis

Nesiritide (Natrecor) is a recombinant form of human brain natriuretic peptide, which causes venous and arterial vasodilation. It does not affect cardiac contractility.1 Nesiritide is approved by the U.S. Food and Drug Administration (FDA) for use in the short-term treatment of hospitalized patients with acutely decompensated heart failure characterized by dyspnea at rest or by clinical evidence of fluid overload.1,2

Name	Dosage	Dose form	Approximate cost*
Nesiritide (Natrecor)	2-mcg-per-kg intravenous bolus followed by 0.01 mcg per kg per minute; 24 to 48 hours' duration	Single-use, 1.5-mg vial	$530 per day
*-Average wholesale cost, based on Red Book, Montvale, N.J.: Medical Economics Data, 2005.

Safety

Initial data from moderately sized controlled trials and large prospective registries suggested that nesiritide is safe.3-5 However, nesiritide has been associated with a transient and significant increase in serum creatinine.1-4 In a pooled analysis,3 nesiritide was associated with an increase in mortality within 30 days of treatment, although the difference was of borderline statistical significance (7.2 versus 4.0 percent; P = .059). Nesiritide has not been compared with vasodilators or diuretics in an adequately powered, randomized clinical study of long-term mortality.3,4 Nesiritide is FDA pregnancy category C.1

Tolerability

The most commonly occurring side effect of nesiritide is symptomatic hypotension.1-6 Nesiritide has been studied in comparison with inotropic agents (primarily intravenous dobutamine [Dobutrex]), noninotropic agents (primarily intravenous nitroglycerin), and placebo. It was associated with significantly fewer arrhythmias than dobutamine7 and with significantly fewer reported headaches than nitroglycerin.6 There were no reported increases in heart rate.7

Effectiveness

Pulmonary capillary wedge pressure decreases within one hour of treatment initiation, is maintained for at least six hours, and returns to preexisting levels when the infusion is discontinued. The effects of nesiritide are additive to the effects of loop diuretics and beta blockers. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may be initiated or continued during nesiritide therapy.1 One study6 showed that nesiritide was similar to typical treatment (e.g., nitroglycerin, milrinone [Primacor], dobutamine) in its effect on symptoms.

Although nesiritide has not received indication for outpatient treatment from the company that developed the product, it has been used for weekly outpatient infusions. A single, nonblinded trial8 comparing this approach with usual care revealed no symptomatic benefit for patients receiving nesiritide. Hospitalizations were less common in the nesiritide group, but this may be because these patients were evaluated weekly by a physician whereas the usual care patients were not.

Price

Nesiritide costs approximately $530 per vial and most patients will need one vial per day for two days. The cost is similar to milrinone (a phosphodiesterase inhibitor), but more expensive than dobutamine, nitroprusside (Nitropress), and nitroglycerin.

Simplicity

Nesiritide is administered as an initial
2-mcg-per-kg intravenous bolus followed by an infusion of 0.01 mcg per kg per minute.4 Dosages greater than 0.01 mcg per kg per minute are associated with hypotension and elevated serum creatinine.1,2 Blood pressure should be monitored closely during nesiritide administration, but an intensive care setting is not mandatory.1,2

Bottom Line

Nesiritide improves short-term hemodynamics in hospitalized patients with acute decompensated heart failure who have not benefited from aggressive treatment with standard care.1,2,5 However, nesiritide may cause renal function to worsen and may increase the risk of death within 30 days.3 Patients should be notified about the potential risks of treatment; nesiritide is not indicated for serial treatments in the outpatient setting.

STEPS drug updates cover Safety, Tolerability, Effectiveness, Price, and Simplicity. Each update provides an independent review of a new medication by authors who have no financial association with the drug manufacturer.

The series coordinator is Allen F. Shaughnessy, Pharm.D., Tufts University Family Medicine Residency Program, Boston, Mass.

---

The Author

Mark Shatsky, D.O., is assistant professor of family medicine at Oregon Health and Science University, Portland, and was previously assistant director of Deaconess Family Medicine Residency, Evansville, Ind.

REFERENCES

1. Natrecor (nesiritide). Package insert. Fremont, Calif.: Scios Inc., 2005. Accessed online November 14, 2005, at: http://www.sciosinc.com/pdf/natrecorpi_final.pdf.

2. Inpatient management of heart failure. Bloomington, Minn.: Institute for Clinical Systems Improvement, 2004. Accessed online November 14, 2005, at: http://www.guideline.gov/summary/summary.aspx?view_id=1&doc_id=4926.

3. Sackner-Bernstein JD, Kowalski M, Fox M, Aaronson K. Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials. JAMA 2005;293:1900-5.

4. Sackner-Bernstein JD, Skopicki HA, Aaronson KD. Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure. Circulation 2005;111:1487-91.

5. Colucci WS, Elkayam U, Horton DP, Abraham WT, Bourge RC, Johnson AD, et al. Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. N Engl J Med 2000;343: 246-53.

6. Publication Committee for the Vasodilation in the Management of Acute CHF Investigators. Intravenous nesiritide vs. nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA 2002;287:1531-40.

7. Burger AJ, Horton DP, LeJemtel T, Ghali JK, Torre G, Dennish G, et al. Effect of nesiritide (b-type natriuretic peptide) and dobutamine on ventricular arrhythmias in the treatment of patients with acutely decompensated congestive heart failure: the PRECEDENT study. Am Heart J 2002;144:1102-8.

8. Yancy CW, Saltzberg MT, Berkowitz RL, Bertolet B, Vijayaraghavan K, Burnham K, et al. Safety and feasibility of using serial infusions of nesiritide for heart failure in an outpatient setting (from the FUSION I trial). Am J Cardiol 2004;94:595-601.

Copyright © 2006 by the American Academy of Family Physicians. This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.