Sustained hemodynamic effects of an infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebo-controlled clinical trial. Natrecor Study Group.
OBJECTIVE
The goal of this study was to further define the role of nesiritide (human b-type natriuretic peptide) in the therapy of decompensated heart failure (HF) by assessing the hemodynamic effects of three doses (0.015, 0.03 and 0.06 microg/kg/min) administered by continuous intravenous (IV) infusion over 24 h as compared with placebo.


BACKGROUND
Previous studies have shown beneficial hemodynamic, neurohormonal and renal effects of bolus dose and 6-h infusion administration of nesiritide in HF patients. Longer term safety and efficacy have not been studied.


METHODS
This randomized, double-blind, placebo-controlled multicenter trial enrolled subjects with symptomatic HF and systolic dysfunction (left ventricular ejection fraction < or =35%). Central hemodynamics were assessed at baseline, during a 24-h IV infusion and for 4 h postinfusion.


RESULTS
One hundred three subjects with New York Heart Association class II (6%), III (61%) or IV (33%) HF were enrolled. Nesiritide produced significant reductions in pulmonary wedge pressure (27% to 39% decrease by 6 h), mean right atrial pressure and systemic vascular resistance, along with significant increases in cardiac index and stroke volume index, with no significant effect on heart rate. Beneficial effects were evident at 1 h and were sustained throughout the 24-h infusion.


CONCLUSIONS
The rapid and sustained beneficial hemodynamic effects of nesiritide observed in this study support its use as a first-line IV therapy for patients with symptomatic decompensated HF.
Division of Cardiovascular Medicine, University of Florida, Gainesville, USA.
R M
RM
Mills
T H
TH
LeJemtel
D P
DP
Horton
C
C
Liang
R
R
Lang
M A
MA
Silver
C
C
Lui
K
K
Chatterjee
D009320:Atrial Natriuretic Factor / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
D002317:Cardiovascular Agents; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor