Nesiritide

Background

-BNP (B-type natriuretic peptide) – hormone produced by the ventricle in response to increased wall stress, hypertrophy and volume overload.
-Nesiritide is a recombinant form of human BNP
-Binds to receptors on smooth muscle and endothelial cells which lead to increases of cyclic GMP resulting in vasodilation
-Primary physiologic effect is arterial, venous and coronary vasodilation; leads to reduction preload/afterload -> incr CO
-No direct inotropic effect; no proarrhythmic properties /

-Promotes diuresis through increased glomerular filtration, filtration fraction

Pharmacokinetics

-Rapid onset of action – effects within 15 minutes

-Long half-life, therefore, no need to wean (can simply stop with effects up to 4 hours afterwards)

-Inactivation via binding to clearance receptor or neutralization by endopeptidases;renal clearance

Administration

-Weight based bolus plus continuous infusion

-Huge Advantage: Do NOT have to be in intensive care unit/PA catheter for use

-No tachyphylaxis; can be given indefinitely

-Careful use of diuretics/other afterload reducing agents

-Biggest disadvantage: Expensive! $375 per day

VMAC Trial

Intravenous Nesiritide vs. Nitroglycerin for Treatment of Decompensated CHF

JAMA, March 27, 2002 - 287 (12) 1531 - 1540

Goal: Compare efficacy of Nesiritide versus NTG or placebo in decompensated CHF

Methods:

-Randomized, double-blind trial; 489 inpatients , 55 hospitals;

-Nesiritide 2-μg/kg bolus, followed by 0.01μg/kg/min

-Titration: increase by 0.005/3hs if PCWP>20, SBP>100

-Inclusion Criteria:

-dyspnea at rest requiring hospitalization and IV tx

-Elevated cardiac filling pressures (PWP > 20, or clinical evid – JVD,CXR, Hx)

-Exclusion: SBP < 90; shock; mechanical ventilation; contraindications to vasodilation

-Primary endpoint – Decrease in PCWP, self-evaluation of dyspnea at 3hrs

Results:

-143 NTG, 204 Nesiritide, 142 placebo;60yo, white males, NYHA III-IV, EF<40, 60% ischemic

-Most patients on medication median time of 24-25hrs.

-Reduction in PWP at 3hrs: -5.8mmHg for nesiritide vs. -3.8mm Hg for NTG (p=0.03)

-Both associated with significantly reduced pulm vasc resistance (Nesiritide effects longer)

-Self assessment of dyspnea (if no PA cath) was not different vs. NTG at 3 and 24hs.

-No sign difference in hypotension, angina; less HA with nesiritide

Conclusions

-Niseritide is as safe and slightly more effective at meeting hemodyn goals / symptom relief

-Intensive/invasive monitoring not necessary

-Potentially very beneficial in settings where IV TNG can not be given/titrated

-Equivalent of adding vasodilator and diuretic (all in one)

-Cost is significantly greater than other medications, justify if save you from ICU admission

-Another med to consider in CHF if not responding to loop diuretics/dopamine

Marco Perez, CCU 1/04