Low-dose nesiritide in human anterior myocardial infarction suppresses aldosterone and preserves ventricular function and structure: a proof of concept study.
BACKGROUND
B-type natriuretic peptide (BNP, nesiritide) has anti-fibrotic, anti-hypertrophic, anti-inflammatory, vasodilating, lusitropic and aldosterone-inhibiting properties but conventional doses of BNP cause hypotension, limiting its use in heart failure.


OBJECTIVE
To determine whether infusion of low-dose BNP within 24 h of successful reperfusion for anterior acute myocardial infarction (AMI) would prevent adverse left ventricular (LV) remodelling and suppress aldosterone.


METHODS
A translational proof-of-concept study was carried out to determine tolerability and biological activity of intravenous BNP at 0.003 and 0.006 microg/kg/min, without bolus started within 24 h of successful reperfusion for anterior AMI. 24 patients with first anterior wall ST elevation AMI and successful revascularisation were randomly assigned to receive 0.003 (n = 12) or 0.006 (n = 12) microg/kg/min of IV BNP for 72 h in addition to standard care during hospitalisation for anterior AMI.


RESULTS
Baseline characteristics, drugs and peak cardiac biomarkers for myocardial damage were similar between both groups. Infusion of BNP at 0.006 microg/kg/min resulted in greater biological activity than infusion at 0.003 microg/kg/min as measured by higher mean (SEM) plasma cGMP levels (8.6 (1) vs 5.5 (1) pmol/ml, p<0.05) and suppression of plasma aldosterone (8.0 (2) to 4.6 (1) ng/dl, p<0.05), which was not seen in the 0.003 microg/kg/min group. LV ejection fraction (LVEF) improved significantly from baseline to 1 month (40 (4)% to 54 (5)%, p<0.05) in the 0.006 group but not in the 0.003 group. Infusion of BNP at 0.006 microg/kg/min was associated with a decrease of LV end-systolic volume index (61 (9) to 43 (8) ml/m(2), p<0.05) at 1 month, which was not seen in the 0.003 group. No drug-related serious adverse events occurred in either group.


CONCLUSIONS
72 h infusion of low BNP at the time of anterior AMI is well tolerated and biologically active. Patients treated with low-dose BNP had improved LVEF and smaller LV end-systolic volume at 1 month.
Chen
H H
HH
Cardiorenal Research Laboratory, Mayo Clinic, Rochester, MN 55904, USA. chen.horng@mayo.edu
Martin
F L
FL
Gibbons
R J
RJ
Schirger
J A
JA
Wright
R S
RS
Schears
R M
RM
Redfield
M M
MM
Simari
R D
RD
Lerman
A
A
Cataliotti
A
A
Burnett
J C
JC
D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000503:physiopathology; D045283:Natriuretic Agents / Q000008:administration & dosage*; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage*; D011994:Recombinant Proteins / Q000008:administration & dosage; D013318:Stroke Volume / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage*; D020257:Ventricular Remodeling / Q000187:drug effects
D000451:Mineralocorticoid Receptor Antagonists; D045283:Natriuretic Agents; D011994:Recombinant Proteins; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain