Impact of acute serum creatinine elevation in patients treated with nesiritide.
BACKGROUND
We assessed the effect of increases in serum creatinine on mortality in nesiritide-treated versus control subjects with acute decompensated heart failure (ADHF).


OBJECTIVE
Mortality effect of nesiritide-related increases in serum creatinine differs from that of standard therapies.


METHODS
Scios Inc., granted unrestricted access to data from all 5 randomized, controlled nesiritide infusion trials completed to date in patients hospitalized with ADHF. We used 2 different definitions of acute serum creatinine increase: >0.3 mg/dL and > 0.5mg/dL within 30 days of study enrollment and determined 30-day mortality risk for nesiritide-treated versus control subjects utilizing each definition.


RESULTS
A total of 1,270 subjects participated in the 5 trials. A >0.3 mg/dL increase in serum creatinine was associated with a significant increase in mortality risk in control subjects, (hazard ratio [HR]: 3.47, 95% confidence interval [CI]: 1.49-8.09) but not in nesiritide-treated subjects (HR: 1.65, 95% CI: 0.90-3.05). Results were similar for a >0.5 mg/dL increase (control HR: 5.12, 95% CI: 2.09-12.57 and nesiritide HR: 1.77, 95% CI: 0.90-3.51). In subjects with >0.3 mg/dL and >0.5 mg/dL increases in serum creatinine, respectively, the 30-day mortality odds ratios for nesiritide relative to control were 0.73 (95% CI: 0.29-1.93) and 0.52 (95% CI: 0.17-1.63) using a stratified Mantel-Haenszel analysis.


CONCLUSIONS
The impact of increased serum creatinine on mortality was attenuated in nesiritide-treated patients compared to control, suggesting that the mechanism and clinical significance of increases in serum creatinine associated with nesiritide treatment may differ from those associated with standard therapies. Further investigation is warranted.
Elkayam
Uri
U
University of Southern California, Los Angeles, California, USA.
Janmohamed
Munir
M
Hatamizadeh
Parta
P
Heywood
J Thomas
JT
Wei
Lee-Jen
LJ
Mills
Roger M
RM
D003404:Creatinine / Q000097:blood*; D005260:Female; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000401:mortality*; D006801:Humans; D007668:Kidney / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D045283:Natriuretic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D020097:Natriuretic Peptide, Brain / Q000009:adverse effects* / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D051437:Renal Insufficiency / Q000097:blood / Q000139:chemically induced / Q000209:etiology; D016019:Survival Analysis
D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain; D003404:Creatinine