Intravenous nesiritide — a recombinant version of the heart's own BNP peptide — rapidly improved heart function, breathing, and clinical status in patients hospitalized with severe heart failure.
67% improved vs 14% placeboTwo-thirds of patients on the higher nesiritide dose showed global clinical improvement within six hours, compared to just 14% of those receiving placebo.
What the researchers found
In the efficacy trial, nesiritide infused at 0.015 and 0.030 μg/kg/min reduced pulmonary-capillary wedge pressure by 6.0 and 9.6 mmHg respectively, compared to a 2.0 mmHg increase with placebo (p < 0.001). Clinical status improved in 60% and 67% of nesiritide patients versus 14% with placebo (p < 0.001). Dyspnea improved in 57% and 53% versus 12% (p < 0.001), and fatigue improved in 32% and 38% versus 5% (p < 0.001).
In the comparative trial, nesiritide's improvements in clinical status, dyspnea, and fatigue were sustained for up to seven days and were comparable to standard intravenous heart failure therapy. The most common adverse effect was dose-related hypotension, which was usually asymptomatic.
Why it matters
This was the pivotal New England Journal of Medicine trial that demonstrated nesiritide — a recombinant form of the body's own BNP peptide — could effectively treat acute decompensated heart failure. It was one of the first major demonstrations that a synthetic natriuretic peptide could be used therapeutically, turning a cardiac biomarker into a treatment. The trial led to FDA approval of nesiritide (brand name Natrecor) for acute heart failure.
The numbers in context
n=432 (127 efficacy + 305 comparative); PCWP reduced 6.0-9.6 mmHg vs +2.0 placebo; 60-67% improved global status vs 14% placebo; 53-57% reduced dyspnea vs 12% placebo; p<0.001
How the study worked
This was a two-part study. The efficacy trial enrolled 127 patients with severe heart failure (pulmonary wedge pressure ≥18 mmHg, cardiac index ≤2.7 L/min/m²) who received Swan-Ganz catheters and were randomized double-blind to placebo or one of two nesiritide doses for six hours. The comparative trial enrolled 305 patients randomized to open-label nesiritide or standard IV heart failure therapy for up to seven days without requiring hemodynamic monitoring.
Who was studied
Hospitalized patients with decompensated congestive heart failure
What this study cannot tell us
The efficacy trial was only six hours long, providing no long-term outcome data. The comparative trial was open-label, introducing potential bias. Neither trial assessed mortality as a primary endpoint. Subsequent larger trials (ASCEND-HF, 2011) would later show that nesiritide, while safe, did not reduce mortality or rehospitalization compared to placebo, tempering initial enthusiasm.
How to read the evidence
Rated strong: randomized controlled trial published in the New England Journal of Medicine with clear, statistically significant results across hemodynamic and clinical endpoints. The efficacy trial was double-blind and placebo-controlled, the gold standard for clinical evidence.
When this study was published
Published in 2000 in the New England Journal of Medicine. This is a historically important trial that led to FDA approval of nesiritide. Subsequent studies (particularly ASCEND-HF in 2011) clarified that the drug didn't improve mortality, which reshaped its clinical role.
The bigger picture
Natriuretic peptides (ANP, BNP, CNP) are the heart's natural counter-regulatory system — they lower blood pressure, reduce fluid overload, and protect the heart. This trial proved the concept that you could give patients a synthetic version of their own cardiac peptide to treat heart failure. While nesiritide's clinical use later became controversial (concerns about kidney function and mortality emerged in subsequent studies), this trial remains a landmark in the history of peptide therapeutics and the broader story of turning biomarkers into drugs.
Questions still open
- Does nesiritide's short-term hemodynamic improvement translate into reduced mortality or rehospitalization in heart failure?
- Could modified natriuretic peptides with longer half-lives or kidney-protective properties improve on nesiritide's clinical profile?
- What is the optimal role for natriuretic peptide therapy in the modern heart failure treatment algorithm?
Common questions
What is nesiritide and how is it related to BNP?
Is nesiritide still used for heart failure today?
Read the original research
Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group.
The New England journal of medicine, 343(4), 246-53
Citation
Colucci, W S; Elkayam, U; Horton, D P; Abraham, W T; Bourge, R C; Johnson, A D; Wagoner, L E; Givertz, M M; Liang, C S; Neibaur, M; Haught, W H; LeJemtel, T H. (2000). Intravenous nesiritide, a natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group.. The New England journal of medicine, 343(4), 246-53.