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Abstract and Introduction
Abstract
Background: Nesiritide (recombinant human B-type natriuretic peptide) has been shown to provide symptomatic and hemodynamic improvement in acute decompensated heart failure. A previous meta-analysis of 3 randomized controlled trials has suggested an increased short-term risk of death with nesiritide use. We performed a meta-analysis of 7 available randomized controlled trials to evaluate the short- and long-term risk of death with nesiritide use for acute decompensated heart failure.
Methods: Seven large randomized controlled nonmortality trials on nesiritide with available data on 30-day mortality were included. Data on 180-day mortality were available only in 4 trials. Mortality data in nesiritide and control arms were extracted from the selected trials and the nesiritide database (Scios Inc, Fremont, CA).
Results: The pooled estimate of the relative risks (RRs) for unadjusted 30- and 180-day mortality revealed no significant differences between the nesiritide arm (RR 1.243, 95% CI 0.798-1.935) and control arm (RR, 0.002, 95% CI 0.798-1.259), respectively).
Conclusions: Unlike a previous analysis, our meta-analysis indicates that nesiritide is not associated with a higher 30- or 180-day mortality. Further analysis of mortality adjusted for confounding variables such as nesiritide dose, duration of infusion, concurrent use of inotropes, heart failure stage, and arrhythmias may reveal subgroups in jeopardy. Large-scale randomized controlled trials powered to evaluate mortality are required to conclusively address these findings.
Introduction
Therapy for acute decompensated heart failure (ADHF) is gauged by symptom relief and reduction in mortality. Among the several intravenous therapies approved for ADHF, nesiritide (recombinant human B-type natriuretic peptide) has gained popularity over the recent years. Nesiritide has venous, arterial, and coronary vasodilatory properties that reduce the preload and afterload, which increase cardiac output without direct inotropic effects. In addition, nesiritide increases glomerular filtration rate and filtration fraction, suppresses the renin-angiotensin-aldosterone axis, and causes natriuresis in patients with ADHF.
Nesiritide has been demonstrated to improve clinical symptoms and hemodynamic parameters in patients with ADHF. Several randomized controlled trials have compared nesiritide to other intravenous therapies or placebo, with outcomes in favor of nesiritide. However, a recent meta-analysis of 3 randomized controlled trials by Bernstein et al has expressed concern of possible short-term (30-day) risk of death after nesiritide use for ADHF. However, no large-scale randomized controlled trials powered to evaluate mortality have been performed to date. There are also no data on long-term safety with nesiritide use.
To address the concern regarding mortality with use of nesiritide, we pooled individual patient level data from 7 large completed randomized controlled nonmortality trials on nesiritide to determine the short-term (30-day) and long-term (180-day) mortality with nesiritide use relative to non-inotrope- or inotrope-based controlled therapies. Our analysis was directed to estimate the mortality risk adjusted to confounding variables such as nesiritide dose, duration of infusion, concurrent use of inotropes, heart failure stage, and arrhythmias, which has not been addressed in previous literature.
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