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Evidence: HighPeptideDiscontinuedRecombinant B-type natriuretic peptideDiscontinued in the USAcute heart failure

Nesiritide

The recombinant form of human B-type natriuretic peptide, sold as Natrecor for acute heart failure until it was discontinued

Nesiritide is a recombinant version of human B-type natriuretic peptide, a hormone made by the heart. Approved in the US as Natrecor for breathlessness in acute heart failure, it failed to change death or readmission in a 7,141-patient trial, and Drugs@FDA now lists it as discontinued.

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Overview

What is it?

Nesiritide is the recombinant form of human B-type natriuretic peptide, given into a vein. FDA declined to approve it in 1999 and asked for more data; the VMAC study then found better haemodynamic effects than intravenous nitroglycerin, with symptomatic low blood pressure in 4% of patients, and it was sold as Natrecor.

Doubts followed. A 2005 meta-analysis of five randomised trials in 1,269 patients found that approved doses raised the risk of worsening kidney function, a creatinine rise of more than 0.5 mg/dL, by about half, with no difference in the need for dialysis. The ASCEND-HF trial was built to settle it: 7,141 people admitted with acute heart failure received nesiritide or placebo for 24 to 168 hours on top of usual care.

More people reported better breathing on nesiritide at 6 hours (44.5% against 42.1%) and 24 hours (68.2% against 66.1%), but neither difference met the trial's prespecified threshold, and death or readmission for heart failure within 30 days was 9.4% against 10.1%. Kidney function did not worsen more often; low blood pressure did. The investigators concluded it could not be recommended for routine use.

Recombinant human BNP is still studied, much of it in Chinese trials such as the ten pooled in a 2026 sepsis review. Meta-analyses report better ejection fraction, urine output and kidney markers around cardiac surgery and after heart attacks, and lower 28-day mortality in sepsis with heart failure. Those analyses pool small trials; the sepsis review graded its mortality evidence as very low certainty, and none approaches ASCEND-HF's size.

The newer uses lean on kidney and rhythm effects. Retrospective studies link it to less atrial fibrillation after bypass surgery, less contrast nephropathy after PCI and less emergency dialysis in cardiorenal syndrome, and in 763 courses for right heart failure in pulmonary hypertension creatinine did not rise. None of these was a large blinded trial.

7,141
Patients in ASCEND-HF
no benefit on death or readmission
9.4% vs 10.1%
30-day death or HF readmission
nesiritide vs placebo
2001
US approval as Natrecor
now discontinued
Science

Mechanism of Action

Nesiritide is recombinant human B-type natriuretic peptide, given intravenously to improve haemodynamics in acute heart failure.

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Vasodilation

It lowers filling pressures quickly, which is why VMAC found better haemodynamics than nitroglycerin, and why low blood pressure is its main side effect.

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Natriuresis

Studies after cardiac surgery report more urine output and lower creatinine with it.

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Kidney uncertainty

A 2005 meta-analysis raised a kidney-harm signal that ASCEND-HF did not confirm.

Evidence

Published Research

These are the studies that describe nesiritide, read from their PubMed abstracts: three human trials, a meta-analysis and a review from the time of its approval.

Human2011

ASCEND-HF: 7,141 patients with acute heart failure

Nesiritide or placebo for 24 to 168 hours with usual care. Better breathing at 6 and 24 hours missed the prespecified significance level; death or heart-failure readmission at 30 days was 9.4% vs 10.1%. Kidney function was not worse; hypotension was commoner.

PMID: 21732835
Human2026

Right heart failure in pulmonary hypertension

In 763 treatment courses for decompensated right heart failure, NT-proBNP fell by a median 47% across pulmonary hypertension groups with creatinine unchanged; blood pressure fell in groups 1 and 4, and adverse events occurred in 0.66%.

PMID: 42512756
Human2023

Cardiorenal syndrome on dialysis

In patients with end-stage kidney disease and type 4 cardiorenal syndrome, rhBNP use was associated with less emergency dialysis (hazard ratio 0.63) and fewer cardiovascular events in a retrospective analysis.

PMID: 38007545
Human2022

Contrast nephropathy after PCI

In elderly patients with acute myocardial infarction undergoing primary PCI, early rhBNP reduced contrast-induced nephropathy and acute heart failure, with no difference in cardiac death or recurrent infarction.

PMID: 36483837
Human2023

Atrial fibrillation after bypass

After propensity matching, postoperative atrial fibrillation after coronary bypass occurred in 18.9% of patients given rhBNP against 37.2% without it, with no more hypotension or ventricular arrhythmia.

PMID: 36084021
Human2022

Kidneys after bypass surgery

In a matched retrospective cohort after coronary bypass, rhBNP was associated with a stronger fall in creatinine and higher urine output over 4 days.

PMID: 36267778
Human2023

Before primary PCI in STEMI

Prophylactic intravenous rhBNP in STEMI patients undergoing primary PCI improved ejection fraction at 1 week and 1 month, with no difference in prognostic events at 6 months.

PMID: 37807319
Review2005

Meta-analysis: kidney function in five trials

Across five randomised trials (1,269 patients), approved doses raised the risk of a creatinine rise above 0.5 mg/dL (relative risk 1.52 against non-inotrope controls). The need for dialysis did not differ.

PMID: 15781736
Review2001

From FDA's first refusal to VMAC

FDA declined approval in 1999 and asked for more data. VMAC then found better haemodynamic effects than intravenous nitroglycerin, no need for invasive monitoring, and symptomatic hypotension in 4%.

PMID: 11322867
Human2008

After maze and mitral valve surgery: 19 patients

A 72-hour infusion of 0.01 µg/kg/min (9 patients) or placebo (10) after bypass did not increase urine output or shorten time to extubation in patients already on a loop-diuretic protocol.

PMID: 18928481
Human2023

Recombinant human BNP after heart attack: 96 patients

Patients given rhBNP after emergency coronary intervention for ST-elevation myocardial infarction had better heart-function measures at one week and six months than those given saline. The report calls itself retrospective.

PMID: 37140291
Review2016

Mortality across trials

A meta-analysis of randomised trials in decompensated heart failure found no increase in mortality with nesiritide against controls, but more hypotension and bradycardia.

PMID: 26739721
Review2025

Perioperative use in cardiac surgery

Across 38 randomised trials with 2,280 patients, perioperative rhBNP was associated with higher ejection fraction (+3.1 points), more urine, better eGFR and lower creatinine, and shorter ventilation and stays.

PMID: 41089773
Review2026

Sepsis with heart failure

Pooling 10 Chinese trials of 1,182 patients, adding rhBNP was associated with lower 28-day mortality (risk ratio 0.73), but the authors graded the certainty of that evidence as very low.

PMID: 41792618
Review2021

After heart attack

A meta-analysis of 9 randomised trials in acute myocardial infarction with heart failure reported higher response rates, shorter stays and higher ejection fraction with rhBNP, without more hypotension or kidney problems.

PMID: 34017399
Dosing

Dosing Data

Natrecor was given as an intravenous bolus followed by a continuous infusion; it is discontinued in the US.

Symptomatic hypotension is the main risk, and was more common than placebo in ASCEND-HF.
ProtocolDoseFrequencyDurationRoute
Trial: VMAC-era approved regimen Human studyPMID 113228672 µg/kg bolus, then 0.01 µg/kg/minContinuous infusionPer clinical responseIntravenous
Trial: ASCEND-HF Human studyPMID 21732835Nesiritide infusion vs placeboContinuous infusion24 to 168 hoursIntravenous

Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.

Weight-based infusion
The regimen was a weight-based bolus and infusion in micrograms per kilogram, run in hospital with blood pressure monitoring.
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Safety

Side Effects & Contraindications

Reported Side Effects

From the trials above.

● Low blood pressure — commoner than placebo in ASCEND-HF, symptomatic in 4% in VMAC
● Worsening kidney function — a raised risk in the 2005 meta-analysis, not confirmed in ASCEND-HF

Contraindications & Cautions

Natrecor is discontinued in the US. These cautions come from its trial record.

● Low blood pressure or shock — hypotension was the adverse effect trials found more often
● Kidney impairment — trial results on kidney function conflicted
● Tested athletes — see the Sport (WADA) row below
Questions

Frequently Asked Questions

?What is nesiritide?

Recombinant human B-type natriuretic peptide, a heart hormone, given by intravenous infusion and sold in the US as Natrecor.

?Did nesiritide work?

In ASCEND-HF, with 7,141 patients, it had a small effect on breathlessness that missed the trial's significance threshold and no effect on death or readmission at 30 days.

?Is nesiritide still available in the US?

Drugs@FDA lists Natrecor as discontinued, as of September 30, 2026.

?Did it harm the kidneys?

A 2005 meta-analysis found a higher risk of worsening kidney function; the much larger ASCEND-HF trial did not.

?Is recombinant BNP still used anywhere?

Yes, in research: recent studies, many of them Chinese trials, test recombinant human BNP in heart failure, cardiac surgery, sepsis and pulmonary hypertension. Most are small or retrospective.

?Does it prevent kidney injury after heart surgery?

A meta-analysis of 38 small trials reported better kidney markers and urine output with perioperative rhBNP. The large ASCEND-HF trial in acute heart failure found kidney function did not worsen more often on nesiritide.

Bibliography

References

  1. [fda] US FDA, Drugs@FDA (openFDA): NATRECOR (nesiritide), Scios LLC, NDA 020920, original approval August 10, 2001, marketing status Discontinued. Read September 30, 2026.
  2. [pubmed] O'Connor CM, et al. "Effect of nesiritide in patients with acute decompensated heart failure." N Engl J Med, 2011;365(1):32-43. PMID: 21732835.
  3. [pubmed] Sackner-Bernstein JD, et al. "Risk of worsening renal function with nesiritide in patients with acutely decompensated heart failure." Circulation, 2005;111(12):1487-91. PMID: 15781736.
  4. [pubmed] Hobbs RE, et al. "An update on nesiritide for treatment of decompensated heart failure." Expert Opin Investig Drugs, 2001;10(5):935-42. PMID: 11322867.
  5. [pubmed] Beaver TM, et al. "Nesiritide following maze and mitral valve surgery." J Card Surg, 2008;23(5):431-6. PMID: 18928481.
  6. [pubmed] Yao L, et al. "Influence of recombinant human B-type natriuretic peptide on improving ventricular function in patients with ST elevation myocardial infarction." Eur Rev Med Pharmacol Sci, 2023;27(8):3420-3429. PMID: 37140291.
  7. [pubmed] Hobbs RE, et al. "Therapeutic potential of nesiritide (recombinant b-type natriuretic peptide) in the treatment of heart failure." Expert Opin Investig Drugs, 1999;8(7):1063-72. PMID: 15992106.
  8. [other] ASHP Drug Shortages, Nesiritide Injection (created June 20, 2018): Janssen is discontinuing Natrecor powder for injection. Read September 30, 2026.
  9. [pubmed] Gong B, et al. "Efficacy and safety of nesiritide in patients with decompensated heart failure: a meta-analysis of randomised trials." BMJ Open, 2016;6(1):e008545. PMID: 26739721.
  10. [pubmed] Shao J, et al. "Effects of Perioperative Recombinant Human Brain Natriuretic Peptide in Patients Undergoing Cardiac Surgery: A Systematic Review and Meta-Analysis." Rev Cardiovasc Med, 2025;26(9):36423. PMID: 41089773.
  11. [pubmed] Liu W, et al. "Clinical efficacy and safety of recombinant human brain natriuretic peptide in the treatment of sepsis complicated by heart failure: a systematic review and meta-analysis." BMC Cardiovasc Disord, 2026;26(1). PMID: 41792618.
  12. [pubmed] Fang J, et al. "A meta-analysis of the clinical efficacy of rhBNP in treating patients with acute myocardial infarction and heart failure." Am J Transl Res, 2021;13(4):2410-2421. PMID: 34017399.
  13. [pubmed] Hu L, et al. "Retrospective Evaluation of Recombinant Human Brain Natriuretic Peptide Therapy for Decompensated Right Heart Failure Across Pulmonary Hypertension Groups." Medicina (Kaunas), 2026;62(7). PMID: 42512756.
  14. [pubmed] Zhou Y, et al. "Impact of recombinant human brain natriuretic peptide on emergency dialysis and prognosis in end-stage renal disease patients with type 4 cardiorenal syndrome." Sci Rep, 2023;13(1):20752. PMID: 38007545.
  15. [pubmed] Zhang YJ, et al. "Protective effect of recombinant human brain natriuretic peptide against contrast-induced nephropathy in elderly acute myocardial infarction patients: A randomized controlled trial." World J Clin Cases, 2022;10(33):12221-12229. PMID: 36483837.
  16. [pubmed] Wei Y, et al. "Effects of Recombinant Human Brain Natriuretic Peptide on Atrial Fibrillation After Coronary Artery Bypass Grafting." J Cardiovasc Pharmacol, 2023;81(1):63-69. PMID: 36084021.
  17. [pubmed] Wang Z, et al. "Effect of recombinant human brain natriuretic peptide on acute kidney injury after coronary artery bypass grafting: a retrospective comparative cohort study." Ann Transl Med, 2022;10(18):973. PMID: 36267778.
  18. [pubmed] Liu Y, et al. "The effects of prophylactic intravenous injection of rhBNP on prognosis in patients with STEMI undergoing PPCI." Cell Mol Biol (Noisy-le-grand), 2023;69(9):156-160. PMID: 37807319.

Sources & Citations

Studies were read from their PubMed abstracts; DailyMed has no current Natrecor label. Read October 7, 2026.

Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.

Last reviewed: 2026-09-30