Nesiritide in acute decompensated heart failure: a pooled analysis of randomized controlled trials.
BACKGROUND
Previous randomized controlled trials (RCTs) evaluating nesiritide for the treatment of acute decompensated heart failure (ADHF) have reported wide variances in mortality hazard ratios for nesiritide vs controls, but these individual trials were neither designed nor powered to evaluate mortality. This study used relevant data from all RCTs of nesiritide in ADHF completed as of June 2006 to independently estimate the effect of nesiritide on 30- and 180-day mortality.


OBJECTIVE
Administration of nesiritide to treat patients with ADHF does not significantly increase mortality at 30 or 180 days.


METHODS
Six trials met prespecified criteria for inclusion in this analysis. Primary data from these trials were obtained from Scios Inc. (Fremont, CA). Statistical models were fitted to estimate 4 effects: dose response, differing control groups, vulnerable subgroup interactions, and time of death relative to nesiritide administration. All models included 4 baseline covariates that were significantly and independently associated with mortality.


RESULTS
Complete covariate data were available in 1472 of 1538 subjects (96%). The risk-adjusted hazard ratio for mortality was 1.05 (95% confidence interval [CI]: 0.85-1.30) at 30 and 1.00 (95% CI: 0.88-1.14) at 180 days with no clear relationship to nesiritide dose. In addition to consistent results across 2 time points, no significant evidence of sensitivity to control group or baseline risk factors was found.


CONCLUSIONS
Currently available data suggest nesiritide does not significantly increase mortality at 30 or 180 days.
Abraham
William T
WT
Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA. william.abraham@osumc.edu
Trupp
Robin J
RJ
Jarjoura
David
D
D000208:Acute Disease; D019317:Evidence-Based Medicine; D006333:Heart Failure / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D045283:Natriuretic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D045283:Natriuretic Agents; D020097:Natriuretic Peptide, Brain