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nesiritide (Natrecor)

Indications: - acute heart failure & cardiogenic shock [8] a) limit use to patients who present to hospital with acute heart failure & dyspnea at rest [4] b) does not improve survival [5] Contraindications: 1) scheduled repetitive use 2) to improve renal function 3) to enhance diuresis [4] Dosage: IV, 1 vial/day for 2 days ($400/vial) Adverse effects: 1) may be better tolerated than IV nitroglycerin 2) less likely than dobutamine to cause tachycardia or arrhythmias 3) may cause more prolonged hypotension than nitroglycerin 4) may be associated with increased risk of death [3] 5) may or may not be associated with renal failure [3,5] Mechanism of action: 1) recombinant type-B natriuretic peptide 2) reduces systemic vascular resistance 3) improves dyspnea & fatigue in patients with CHF Clinical trials: - [7] nesiritide does not improve dyspnea, reduce rehospitalization or improve all-cause mortality in patients with acute heart failure [7] Notes: Manufacturer: Scios

Specific

Nesiritide Parenteral

General

natriuretic hormone recombinant protein; chimer vasodilator agent

Properties

COMPARTMENT: extracellular compartment MOTIF: cysteine residue {X} MODIFICATION: cysteine residue {X2} cysteine residue {X2} MODIFICATION: cysteine residue {X}

References

  1. Prescriber's Letter 8(9):50 2001
  2. Journal Watch 25(11):89, 2005 Sackner-Bernstein JD, Kowalsi 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 293(April 20): 1900, 2005
  3. FDA MedWatch http://www.fda.gov/medwatch/SAFETY/2005/safety05.htm#natrecor http://www.fda.gov/medwatch/safety/2005/safety05.htm#Natrecor2
  4. Journal Watch 25(15):124, 2005 http://www.natrecor.com/pdf/Braunwald_Panel_Release_&_Report.pdf
  5. Witteles RM et al, Impact of nesritide on renal function in patients with acute decompensated heart failure and pre-existing renal dysfunction: A randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol 2007, 50:1835 PMID: 17980284 - Silver MA and Yancy CW Using homeostatic peptides in decompenstated heart failure: A reasonable paradigm but a flawed practice? J Am Coll Cardiol 2007, 50:1841 PMID: 17980249
  6. Yancy CW et al for the FUSION II Investigators Safety and efficacy of outpatient nesiritide in patients with advanced heart failure: Results of the Second Follow-Up Serial Infusions of Nesiritide (FUSION II) trial. Circ Heart Fail 2008, 1:9 PMID: 19808265 - Yancy CW et al for the FUSION II Investigators The Second Follow-up Serial Infusions of Nesiritide (FUSION II) trial for advanced heart failure: study rationale and design. Am Heart J. 2007 Apr;153(4):478-84. PMID: 17383282
  7. O'Connor CM Effect of Nesiritide in Patients with Acute Decompensated Heart Failure N Engl J Med 2011; 365:32-43 PMID: 21732835
  8. Medical Knowledge Self Assessment Program (MKSAP) 17, American College of Physicians, Philadelphia 2015