Does nesiritide reduce mortality and readmission in decompensated heart failure?

AT THE BEDSIDE

EVIDENCE-BASED MEDICINE

Does nesiritide reduce mortality and readmission in decompensated heart failure?

Wanderley Marques Bernardo^I; Fábio Tanzillo Moreira^II

^ICoordinator, Projeto Diretrizes AMB-CFM; Professor of Evidence-Based Medicine, UNILUS, Santos, SP, Brazil

^IIGraduate Student, Faculdade de Ciências Médicas de Santos (UNILUS), Santos, SP, Brazil

INTRODUCTION

Heart failure (HF) is characterized by insufficient cardiac output to supply adequate perfusion to the peripheral demands. When decompensated, it can cause various systemic effects, depending on the type of presentation. The patient may have only a low cardiac output, or may have a large pulmonary vascular congestion, causing acute pulmonary edema and clinically important dyspnea.

Nesiritide is a recombinant form of brain natriuretic peptide (BNP), secreted when the walls of the heart's ventricles are dilated, and its use was approved in 2001 by the FDA for the treatment of decompensated HF. It has vasodilatory properties, causing reduced pre-and afterload, decreased pulmonary capillary pressure, and increased cardiac output without inotropic effects^1,2 and without causing arrhythmias³.

The objective of this review is to evaluate whether the use of nesiritide brings benefit or harm to patients presenting to the emergency department with dyspnea for HF decompensation.

METHOD

A systematic review was conducted in the MEDLINE database to find the best evidence available with the following strategy: [(Natriuretic Peptide, Brain OR Nesiritide) AND (Dyspnea OR Heart failure)]. The Therapy/Narrow filter was used through the Clinical Queries interface.

Each retrieved study was evaluated by title and summary. The selected studies met the following inclusion criteria: randomized clinical trial; use of nesiritide compared with placebo (both combined with standard therapy) in patients presenting to the emergency department with decompensated HF/dyspnea; and written in English, Spanish, or Portuguese. Only studies with a Jadad et al.⁴ score greater than or equal to three were included in the final selection and data analysis.

All variables were analyzed through the CATmaker software, using the difference in absolute risk (AR), with 95% confidence interval (95% CI), and the number needed to treat (NNT) or number needed to harm (NNH). Metaanalysis was performed using the Review Manager 5.1.2 software.

RESULTS

The literature review was completed in August 2011. We retrieved 411 articles, but only seven^5-11 met the inclusion criteria. After analysis of the selected articles, two were excluded from the final selection; one⁵ for not having a placebo group for comparison, and the other¹¹ for not providing absolute data on the outcomes, preventing the calculation of risk difference.

In the study by Colucci et al.⁹, two doses of nesiritide were tested (0.015 and 0.030 µg/kg/min) and compared to placebo. Mills et al.¹⁰ tested three doses (0.015, 0.03, and 0.06 µg/kg/min) compared to placebo.

MORTALITY

Four studies^6-8,10 presented data on mortality (Figures 1 and 2). There was no statistically significant difference in risk for both the effect of individual studies and the overall effect.

READMISSION

Of the three studies^6-8 evaluating the number of readmissions, only one study⁸ showed a significant benefit of nesiritide. However, there was no significant difference in the overall effect (Figures 3 and 4).

CONCLUSION

Analysis of best available evidence shows that the use of nesiritide is safe because it did not cause significant differences in mortality and readmission rates.

REFERENCES

• 1. Clarkson PB, Wheeldon NM, Macleod C, Coutie W, MacDonald TM. Brain natriuretic peptide: effect on left ventricular filling patterns in healthy subjects. Clin Sci (Lond) 1995;88(2):159-64.
• 2. Zellner C, Protter AA, Ko E, Pothireddy MR, DeMarco T, Hutchison SJ et al Coronary vasodilator effects of BNP: mechanisms of action in coronary conductance and resistance arteries. Am J Physiol. 1999;276(3 Pt 2):H1049-57.
• 3. Burger AJ, Horton DP, LeJemtel T, Ghali JK, Torre G, Dennish G et al Prospective Randomized Evaluation of Cardiac Ectopy with Dobutamine or Natrecor Therapy. 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(6):1102-8.
• 4. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ et al Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17(1):1-12.
• 5. Sakr A, Hahn P, Donohue T, Ghantous A. Nesiritide in the initial management of acute decompensated congestive heart failure. Conn Med. 2008;72(9):517-23.
• 6. O'Connor CM, Starling RC, Hernandez AF, Armstrong PW, Dickstein K, Hasselblad V, et al. Effect of nesiritide in patients with acute decompensated heart failure. N Engl J Med. 2011;365(1):32-43.
• 7. Miller AH, Nazeer S, Pepe P, Estes B, Gorman A, Yancy CW. Acutely decompensated heart failure in a county emergency department: a double-blind randomized controlled comparison of nesiritide versus placebo treatment. Ann Emerg Med. 2008;51(5):571-8.
• 8. Peacock WF 4th, Holland R, Gyarmathy R, Dunbar L, Klapholz M, Horton DP et al Observation unit treatment of heart failure with nesiritide: results from the proaction trial. J Emerg Med. 2005;29(3):243-52.
• 9. 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. Nesiritide Study Group. N Engl J Med. 2000;343(4):246-53. Erratum in: N Engl J Med 2000;343(20):1504. N Engl J Med 2000;343(12):896.
• 10. Mills RM, LeJemtel TH, Horton DP, Liang C, Lang R, Silver MA et al Sustained hemodynamic effects of an infusion of nesiritide (human btype natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group. J Am Coll Cardiol. 1999;34(1):155-62.
• 11. Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF). Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized controlled trial. JAMA. 2002;287(12):1531-40. Erratum in: JAMA. 2002;288(5):577.

Publication Dates

• Publication in this collection
  04 May 2012
• Date of issue
  Apr 2012