Context Nesiritide improves symptoms in patients with acutely decompensated
heart failure compared with placebo and appears to be safer than dobutamine.
Its short-term safety relative to standard diuretic and vasodilator therapies
is less clear.
Objective To investigate the safety of nesiritide relative to noninotrope-based
control therapies, primarily consisting of diuretics or vasodilators.
Data Sources Primary reports of completed clinical trials as of December 2004 were
obtained from the US Food and Drug Administration (FDA), the study sponsor
(Scios Inc), a PubMed literature search using the terms nesiritide, clinical trials, and humans, and a manual search of annual meetings of 3 heart associations.
Study Selection Of 12 randomized controlled trials evaluating nesiritide, 3 met all
inclusion criteria: randomized double-blind study of patients with acutely
decompensated heart failure, therapy administered as single infusion (≥6
hours), inotrope not mandated as control, and reported 30-day mortality.
Data Extraction Data were extracted from FDA and sponsor documents and corroborated
with published articles when available. Thirty-day survival was assessed by
meta-analysis using a fixed-effects model and time-dependent risk by Kaplan-Meier
analysis with Cox proportional hazards regression modeling. Where deaths were
described within a range of days after treatment, an extreme assumption was
made favoring nesiritide over control therapy, an approach relevant to the
Data Synthesis In the 3 trials, 485 patients were randomized to nesiritide and 377
to control therapy. Death within 30 days tended to occur more often among
patients randomized to nesiritide therapy (35 [7.2%] of 485 vs 15 [4.0%] of
377 patients; risk ratio from meta-analysis, 1.74; 95% confidence interval
[CI], 0.97-3.12; P = .059; and hazard ratio after adjusting
for study, 1.80; 95% CI, 0.98-3.31; P = .057).
Conclusions Compared with noninotrope-based control therapy, nesiritide may be associated
with an increased risk of death after treatment for acutely decompensated
heart failure. The possibility of an increased risk of death should be investigated
in a large-scale, adequately powered, controlled trial before routine use
of nesiritide for acutely decompensated heart failure.