BNP and nesiritide
B-type natriuretic peptide (BNP) and nesiritide (Natrecor), the recombinant drug
Written by Aaron CuhaReviewed Sep 2026
Also known as: BNP, Brain natriuretic peptide, B-type natriuretic peptide, Nesiritide, Natrecor, NT-proBNP
The heart hormone that became both the standard blood test for heart failure and a drug that failed. In ASCEND-HF, 7,141 people were randomised to nesiritide or placebo: dyspnoea barely moved, death and rehospitalisation did not change, and the product is listed Discontinued in Drugs@FDA.
Overview
B-type natriuretic peptide is a 32 amino acid peptide, sequence SPKMVQGSGCFGRKMDRISSSSGLGCKVLRRH, released by ventricular muscle under wall stress. Most readers meet it twice over and the two meanings get confused, so the distinction comes first. As a biomarker, BNP and its inactive precursor fragment NT-proBNP are measured in blood to diagnose and grade heart failure, and that use is routine and well supported. As a drug, recombinant BNP is nesiritide, sold as Natrecor, and that is a different story.
Nesiritide was approved in 2001 on dyspnoea relief and haemodynamic grounds. Two 2005 meta-analyses then raised alarms: one found an increased risk of worsening renal function (relative risk 1.52, 95 percent confidence interval 1.16 to 2.00 against non-inotrope control), the other found a trend toward more deaths within 30 days (7.2 percent versus 4.0 percent, risk ratio 1.74, 95 percent confidence interval 0.97 to 3.12). The manufacturer funded a trial large enough to settle it. ASCEND-HF randomised 7,141 people hospitalised with acute heart failure to nesiritide or placebo on top of standard care. Dyspnoea improved slightly more on nesiritide at 6 hours (44.5 versus 42.1 percent) and 24 hours (68.2 versus 66.1 percent), neither reaching the prespecified significance threshold. Rehospitalisation for heart failure or death within 30 days was 9.4 percent versus 10.1 percent, absolute difference -0.7 percentage points, 95 percent confidence interval -2.1 to 0.7. Renal function did not worsen, which cleared the drug of the earlier charge, but hypotension increased and the authors wrote that nesiritide cannot be recommended for routine use. The trial was funded by Scios, the manufacturer.
Regulatory status, re-checked on 11 September 2026: NATRECOR, application NDA 020920, Scios LLC, is listed Discontinued, and the Drugs@FDA record carries the Federal Register determination that the product was not discontinued or withdrawn for safety or effectiveness reasons. No other nesiritide product is listed. The openFDA drug label database returned no current Natrecor label.
Mechanism of action
In humans, BNP binds NPR-A (gene NPR1), the same particulate guanylyl cyclase receptor as ANP, raising cyclic GMP to produce vasodilation, natriuresis and suppression of renin and aldosterone. That is the physiology that made a recombinant version look promising in acute heart failure. The biomarker use rests on different ground: ventricular stretch increases proBNP production, which is cleaved into active BNP and the inactive NT-proBNP fragment, and the concentration of either in blood tracks the degree of cardiac stress.
Human evidence
Unusually complete, and mostly negative. One 7,141 person randomised placebo-controlled trial, preceded by two meta-analyses that raised safety questions and followed by subanalyses of the same dataset. Separately, BNP and NT-proBNP have a very large human literature as diagnostic and prognostic blood tests.
- ASCEND-HF (2011): 7,141 randomised. Co-primary endpoints of dyspnoea change and 30 day death or rehospitalisation were both effectively null. Death from any cause at 30 days was 3.6 percent with nesiritide and 4.0 percent with placebo. Hypotension was more common on nesiritide. Manufacturer funded.
- Pooled analysis of 3 randomised trials (2005): 30 day death 7.2 percent versus 4.0 percent, risk ratio 1.74, 95 percent confidence interval 0.97 to 3.12.
- Meta-analysis of 5 randomised trials (2005): worsening renal function relative risk 1.52, 95 percent confidence interval 1.16 to 2.00. ASCEND-HF did not confirm this in 7,141 people, which is a case of a large trial overturning a meta-analysis of small ones.
- The renal subanalysis of ASCEND-HF and its accompanying editorial closed the cardiorenal rationale for the drug.
- As a biomarker rather than a drug, NT-proBNP was measured in the ASCEND-HF population and tracks morbidity and mortality, with body mass index modifying the relationship.
What this does not tell you: ASCEND-HF tested one drug at one dose range in acute heart failure in hospital, and says nothing about the natriuretic peptide system as a target more generally. Neither the trial nor its subanalyses can distinguish a drug that does nothing from a drug whose small haemodynamic benefit is cancelled by hypotension. The biomarker data are observational by nature: a high BNP identifies risk, it does not tell you what to do about it.
Reading the research record
This page exists because the arc is the lesson. A hormone with an impeccable mechanism was approved in 2001 on symptom and haemodynamic endpoints, sold widely, questioned by two 2005 meta-analyses of small trials, tested properly in 7,141 people at the manufacturer's expense, found not to help, and finally discontinued. Drugs@FDA still records the Federal Register determination that the withdrawal was not for safety or effectiveness reasons, which is a regulatory statement about the terms of withdrawal rather than a verdict on ASCEND-HF.
Two things are worth carrying away. First, a company funding the trial that killed its own product is exactly how this is supposed to work, and it is worth saying plainly in a field where sponsor-funded trials are usually mentioned only as a criticism. Second, the same molecule remains enormously useful in the form nobody markets as a peptide: the BNP and NT-proBNP blood tests. The research file behind this page could not resolve the ASCEND-HF primary results publication and asked that it be resolved before citing; it resolves to PMID 21732835, New England Journal of Medicine, 7 July 2011, and that correction is recorded here.
The evidence, charted
Fig. 1 · evidence composition
6of 7 citations (86%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 5 distinct years, 2005 to 2018, counted from the citation list on this page. The newest citation on file is from 2018, more than five years ago; the published record may have gone quiet.
Fig. 3 · legal status at a glance
US
Approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 3 of 4, prescription route in 0, not approved in 1. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Key studies & citations
- Human2011
Effect of nesiritide in patients with acute decompensated heart failure
ASCEND-HF: 7,141 people hospitalised with acute heart failure randomised to nesiritide or placebo for 24 to 168 hours on top of standard care. Dyspnoea improvement 44.5 versus 42.1 percent at 6 hours and 68.2 versus 66.1 percent at 24 hours, neither meeting the prespecified threshold. Rehospitalisation or death within 30 days 9.4 versus 10.1 percent (difference -0.7 percentage points, 95 percent confidence interval -2.1 to 0.7). No excess worsening renal function; more hypotension. Funded by Scios, the manufacturer.
New England Journal of Medicine - Human2005
Short-term risk of death after treatment with nesiritide for decompensated heart failure: a pooled analysis of randomized controlled trials
Pooled analysis of 3 randomised trials, 485 patients on nesiritide and 377 on control. Death within 30 days occurred in 7.2 percent versus 4.0 percent, risk ratio 1.74, 95 percent confidence interval 0.97 to 3.12, p = 0.059. The authors called for a large adequately powered trial before routine use, which is what ASCEND-HF became.
JAMA - Human2005
Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure
Meta-analysis of 5 randomised studies, 1,269 patients. FDA-approved doses of nesiritide increased worsening renal function against non-inotrope control, relative risk 1.52, 95 percent confidence interval 1.16 to 2.00, p = 0.003. There was no difference in the need for dialysis. ASCEND-HF later found no excess renal harm in 7,141 people.
Circulation - Human2009
Standardizing care for acute decompensated heart failure in a large megatrial: the approach for the Acute Studies of Clinical Effectiveness of Nesiritide in Subjects with Decompensated Heart Failure (ASCEND-HF)
The design and conduct paper for ASCEND-HF, describing how background heart failure care was standardised across the trial so that the nesiritide comparison would be interpretable.
American Heart Journal - Review2014
Renal subanalysis of the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF): the end of nesiritide as a cardiorenal therapeutic?
Editorial accompanying the ASCEND-HF renal subanalysis. Its title states the conclusion the field drew: the renal case for nesiritide did not survive the trial.
Circulation - Human2018
Interaction of Body Mass Index on the Association Between N-Terminal-Pro-b-Type Natriuretic Peptide and Morbidity and Mortality in Patients With Acute Heart Failure: Findings From ASCEND-HF
Analysis within the ASCEND-HF population of NT-proBNP as a prognostic marker and how body mass index changes its interpretation. This is the biomarker use of the peptide, which is separate from its failed use as a drug.
Journal of the American Heart Association - Human2011
A Study Testing the Effectiveness of Nesiritide in Patients With Acute Decompensated Heart Failure (ASCEND-HF)
Registry record: phase 3, 7,141 participants enrolled, completed, lead sponsor Scios Inc. No results are posted in the registry record itself as of 11 September 2026.
ClinicalTrials.gov
Frequently asked questions
What is the difference between BNP the blood test and nesiritide the drug?
They are the same peptide used two ways. The blood test measures the BNP your own heart releases, or the inactive NT-proBNP fragment, to detect and grade heart failure. Nesiritide is a recombinant version given by infusion as a treatment. The test is routine; the drug is discontinued.
Why was nesiritide discontinued?
After ASCEND-HF, a 7,141 person randomised trial funded by the manufacturer, found that it did not reduce death or rehospitalisation and produced only a small non-significant improvement in breathlessness, while increasing hypotension. The Drugs@FDA record lists NATRECOR as Discontinued, with a Federal Register determination that it was not withdrawn for safety or effectiveness reasons.
Did nesiritide damage the kidneys?
A 2005 meta-analysis of 5 small randomised studies found a 52 percent higher relative risk of worsening renal function. ASCEND-HF, which was far larger, found no excess: 31.4 percent versus 29.5 percent, odds ratio 1.09, 95 percent confidence interval 0.98 to 1.21. The large trial is the better evidence and it did not confirm the kidney signal.
Is a high BNP result dangerous in itself?
A raised BNP or NT-proBNP marks cardiac stress and predicts worse outcomes, which is why it is measured. It is a signal of the underlying condition rather than something to treat directly, and giving the peptide as a drug did not improve outcomes when it was tested.