May 25, 2005
Manhasset, NY-
Nesiritide is a recombinant form of human B-type natriuretic
peptide (hBNP) that improves symptoms in patients with acutely
decompensated heart failure. It was approved by the US Food and
Drug Administration (FDA) based on its ability to reduce
symptoms of dyspnea and left ventricular filling pressure
relative to placebo within 3 hours of administration. A pooled
analysis of randomized controlled trials was studied by Jonathan
Sackner-Bernstein M.D. et al from Northshore University Hospital
in New York and published in the April 20, 2005 issue of The
Journal of American Medical Association. The study concluded
that nesiritide may be associated with an increased risk of
death after treatment for acutely decompensated heart failure.
Previous studies
have shown nesiritide to be associated with a heightened risk of
renal failure. To determine if this worsening of renal failure
is associated with an increased risk of death, this study pooled
available individual patient data from completed randomized
controlled trials to determine the safety of nesiritide therapy.
Three randomized, double-blind controlled trials used
noninotrope-based control therapy and provided at lease 30-day
follow- up of the patient’s status. The three studies were the
Nesiritide Study Group Efficacy Trial (NSGET), Vasodilation in
the Management of Acute Congestive heart failure (VMAC) and the
Prospective Randomized Outcomes Study of Acutely Decompensated
Congestive Heart Failure Treated initially in Outpatients with
Natrecor (PROACTION).
The crude risk of
mortality within the first 30 days after randomization was
significantly higher for patients in VMAC than for patients in
PROACTION (36 [7.2%] of 498 vs. 6 [2.5%] of 237 patients; RR,
2.86; 95% CI 1.22-6.67; P=0.01). The intermediate risk group was
NSGET (8 [6.3%] of 127 patients; RR 2.49; 95% CI, 0.88-7.01;
P=0.09). The crude 30 day mortality was higher for nesiritide
than for control therapy (35 [7.2%] of 485 vs. 15 [4.0%] pf 377;
RR, 1.81; 95% CI, 1.01-3.27; P=0.04). Meta-analysis suggested a
higher risk with nesiritide therapy (RR 1.74; 95% CI, 0.97-3.12;
P=0.059)
The three trials
in these analyses are the only double-bind studies to evaluate
the 30- day outcomes associated with nesiritide therapy for
patients with acutely decompensated heart failure. The analysis
of these studies suggests nesiritide therapy may be associated
with meaningful mortality risk. Although there is an association
between nesiritide and increased mortality, a more adequately
powered prospective trial is necessary for definitive results.
The possibility
of this risk implies that nesiritide may not be an optimal
choice as first-line therapy for acutely decompensated heart
failure. This study advises to consider reserving use of this
agent to situations in which a combination of diuretics and
nitroglycerin has proven inadequate.
Co-authors:
Marcin Kowalski, MD, Marshal Fox MD, Keith Aaronson, MD, MS |