Carperitide
Recombinant human ANP, infused for acute heart failure in Japan since 1995: used in more than half of Japanese admissions, with outcome evidence that points both ways
Carperitide is recombinant α-human atrial natriuretic peptide, the same 28-amino-acid hormone the heart releases when it is stretched. It dilates vessels and makes the kidneys excrete sodium and water, and because its plasma half-life is about three minutes it is given as a continuous intravenous infusion. Japan approved it for acute heart failure in 1995 and it became the most-used drug in that setting there, but its evidence is mostly observational and contradictory, and its one sizeable randomised trial stopped early without showing benefit. It has never been approved in the US or the EU.
What is it?
The heart's atria release atrial natriuretic peptide when they are stretched. It relaxes blood vessels, makes the kidneys excrete sodium and water, and suppresses renin and aldosterone. Carperitide is that hormone made by recombinant technology, 28 amino acids with one disulfide ring. It is cleared within minutes: in 1986 studies in men, plasma levels fell with a half-life of 2.5 minutes after a bolus and 3.2 minutes after an infusion was stopped, so it is always given as a continuous intravenous infusion.
Japan approved carperitide for acute heart failure in 1995, and it became the country's most-used drug for it: one hospital study found it given to more than half of all acute heart failure patients. In a six-year registry of 3,777 patients, treatment improved the clinical condition in 82%, and in a registry of patients with preserved blood pressure and congestion 83.2% recovered from the acute phase on carperitide alone. Its main adverse effect is the one its mechanism predicts: falls in blood pressure, most often in the first hours of infusion.
Whether it changes outcomes is unsettled, and the evidence runs both ways. A propensity-matched analysis of 367 pairs found higher in-hospital mortality with carperitide (odds ratio 2.13), especially in older patients, while a pooled Japanese cohort of 2,435 patients linked low doses to lower one-year cardiovascular and all-cause mortality. A small randomised trial of 49 patients reported fewer deaths and readmissions over 18 months with low-dose infusions (11.5% against 34.8%), but the larger LASCAR-AHF trial of 247 patients found no reduction in long-term mortality or heart failure admissions and a greater fall in kidney function; it was stopped early and was underpowered.
Head-to-head comparisons have not favoured it: tolvaptan produced more urine with fewer treatment-limiting adverse events, and nitrate infusions improved haemodynamics more with similar one-year outcomes. Outside heart failure, a randomised trial in 668 patients having coronary bypass surgery found that carperitide infused from the start of bypass reduced post-operative atrial fibrillation. Carperitide has never been approved by FDA or EMA; nesiritide, recombinant BNP, filled a similar role in the US.
Mechanism of Action
Carperitide is the body's own atrial natriuretic peptide given as a drug, so it does what the hormone does, briefly.
NPR-A and cyclic GMP
Natriuretic peptides act through the NPR-A receptor's guanylyl cyclase, raising cyclic GMP; during haemofiltration, lower plasma carperitide went with lower cyclic GMP, the second messenger of its effects.
Vasodilation, natriuresis, diuresis
Natriuretic peptides dilate vessels, promote sodium and water excretion and inhibit renin and aldosterone, lowering cardiac filling pressures; the same vasodilation causes its main adverse effect, hypotension.
Minutes in the circulation
Plasma α-hANP falls with a half-life of about 2.5 to 3.2 minutes, so the effect lasts only while it is infused; haemofiltration also removes some of it.
Atrial rhythm after surgery
In coronary bypass surgery, infusion from the start of cardiopulmonary bypass reduced post-operative atrial fibrillation, and not using carperitide was among the independent risk factors.
Published Research
These are the studies behind carperitide, read from their PubMed abstracts. Nearly all come from Japan, most are registries or retrospective analyses, and only a few are randomised, which is why its effect on outcomes is still debated.
LASCAR-AHF: the randomised outcome trial
At nine sites, 247 patients with acute heart failure received low-dose intravenous carperitide with standard treatment or standard treatment alone for 72 hours, open label. Carperitide did not reduce long-term mortality or heart failure hospitalisation, and kidney function fell more on it (eGFR difference -3.9 mL/min/1.73 m², 95% CI -7.0 to -0.8). Enrolment stopped early, leaving the trial underpowered and inconclusive.
A small randomised trial: 49 patients
Low-dose carperitide (0.01 to 0.05 µg/kg per minute) infused for 72 hours as initial treatment was compared with standard treatment without it. Over 18 months, death or readmission occurred in 11.5% against 34.8% (P=0.036); randomisation to carperitide, higher pre-treatment blood pressure and beta-blocker use predicted freedom from events.
COOPERATE-HF-J: 2,435 patients pooled
In two pooled Japanese cohorts, low-dose carperitide was associated with lower cardiovascular and all-cause mortality within a year of admission after adjustment (hazard ratios 0.696 and 0.791). The authors call for randomised trials to find which doses help.
Propensity-matched: higher in-hospital mortality
Carperitide had been used in more than half of Japanese acute heart failure patients. In 367 propensity-matched pairs from three hospitals, it was associated with higher in-hospital mortality (odds ratio 2.13, 95% CI 1.17 to 3.85), more so in older patients (2.93).
A six-year registry of 3,777 patients
Patients received a median 0.085 µg/kg per minute for a median 65 hours. Adverse reactions occurred in 16.9%, most often low blood pressure (9.5%) in the first 3 hours, from which 96% recovered without specific treatment; 7-day mortality was 11.4%, predicted by age, Killip class, kidney dysfunction, low blood pressure and vasopressor use, and 82% improved clinically.
First-line use with preserved blood pressure
In an observational study of patients with systolic pressure of 120 mmHg or more, pulmonary congestion and breathlessness, half started at 0.025 to 0.05 µg/kg per minute. Carperitide alone restored the acute phase and eased breathlessness in 1,524 patients (83.2%); adverse reactions affected 4.64%, most often hypotension (3.55%).
AVCMA: tolvaptan against carperitide
In a randomised trial in acute decompensated heart failure, urine volume was higher with tolvaptan, blood pressure fell more with carperitide, and adverse events such as worsening heart failure and hypotension requiring discontinuation were less frequent with tolvaptan (P=0.027), which also cost less.
Carperitide against nitrate infusions
In 52 patients treated in intensive care between 1997 and 2007, nitrates tended to improve haemodynamics more than carperitide, but the in-hospital fall in BNP, length of stay and cardiac events over a year did not differ.
Atrial fibrillation after bypass surgery: 668 randomised
Patients having isolated coronary bypass grafting received carperitide or saline from the start of cardiopulmonary bypass and were monitored for a week. Perioperative carperitide reduced post-operative atrial fibrillation, and not using it was an independent risk factor along with age of 70 or more and emergency surgery.
Removal by haemofiltration
In 11 critically ill patients receiving carperitide who needed continuous venovenous haemofiltration, the filter removed infused hANP, though less than whole-body clearance; haemofiltration slightly lowered plasma hANP and cyclic GMP and raised arterial pressure.
Plasma kinetics of alpha-hANP in man
During an infusion of synthetic α-hANP, plasma levels reached about 1,185 and 1,117 pg/mL at 30 and 40 minutes; after it stopped, they fell by first-order kinetics with a half-life of 3.2 ± 0.4 minutes, in line with the brief effects of the peptide.
Half-life after a bolus
After an intravenous bolus of 100 µg α-hANP, immunoreactive levels in plasma fell rapidly and exponentially over the first 10 minutes (half-life 2.5 minutes), then more slowly, reaching basal values 30 minutes after injection.
Dosing Data
Carperitide is given only as a continuous intravenous infusion in hospital. Doses in the studies ranged widely.
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.
Side Effects & Contraindications
Reported Side Effects
From the registries and trials above.
Contraindications & Cautions
Carperitide's evidence suggests these cautions; the treating team decides.
Legal Status
Carperitide is approved in Japan and not in the US or the EU.
Frequently Asked Questions
?Is carperitide the same as ANP?
Yes. It is recombinant α-human atrial natriuretic peptide, identical to the 28-amino-acid hormone the heart releases. Our separate ANP entry describes the hormone itself.
?Does carperitide improve survival in heart failure?
That is unsettled. One propensity-matched analysis linked it to higher in-hospital mortality and a pooled cohort linked low doses to lower one-year mortality; its randomised LASCAR-AHF trial found no long-term benefit but stopped early and was underpowered.
?Where is carperitide approved?
In Japan, since 1995, for acute heart failure. FDA's Drugs@FDA database and EMA's register have no entry for it.
?Why is it given as an infusion?
Its plasma half-life is only about 2.5 to 3.2 minutes, so its effects stop within minutes of ending the infusion.
?What is its main side effect?
Low blood pressure, which occurred in 9.5% of a 3,777-patient registry, mostly in the first three hours, and usually resolved without specific treatment.
?How does it compare with nesiritide?
Both are recombinant natriuretic peptides given by infusion for acute heart failure: carperitide is ANP and was approved in Japan, nesiritide is BNP and was approved in the US.
References
- [pubmed] Honda S, et al. "Effect of low-dose administration of carperitide for acute heart failure: the LASCAR-AHF trial." Eur Heart J Acute Cardiovasc Care, 2025;14(2):83-92. PMID: 39656827.
- [pubmed] Hata N, et al. "Effects of carperitide on the long-term prognosis of patients with acute decompensated chronic heart failure: the PROTECT multicenter randomized controlled study." Circ J, 2008;72(11):1787-93. PMID: 18812677.
- [pubmed] Nogi K, et al. "Effect of carperitide on the 1 year prognosis of patients with acute decompensated heart failure." ESC Heart Fail, 2022;9(2):1061-1070. PMID: 35118813.
- [pubmed] Matsue Y, et al. "Carperitide Is Associated With Increased In-Hospital Mortality in Acute Heart Failure: A Propensity Score-Matched Analysis." J Card Fail, 2015;21(11):859-64. PMID: 25999241.
- [pubmed] Suwa M, et al. "Multicenter prospective investigation on efficacy and safety of carperitide for acute heart failure in the 'real world' of therapy." Circ J, 2005;69(3):283-90. PMID: 15731532.
- [pubmed] Nomura F, et al. "Multicenter prospective investigation on efficacy and safety of carperitide as a first-line drug for acute heart failure syndrome with preserved blood pressure: COMPASS: Carperitide Effects Observed Through Monitoring Dyspnea in Acute Decompensated Heart Failure Study." Circ J, 2008;72(11):1777-86. PMID: 18832779.
- [pubmed] Suzuki S, et al. "Acute heart failure volume control multicenter randomized (AVCMA) trial: comparison of tolvaptan and carperitide." J Clin Pharmacol, 2013;53(12):1277-85. PMID: 24142853.
- [pubmed] Mizutani T, et al. "Comparison of nitrite compounds and carperitide for initial treatment of acute decompensated heart failure." Int Heart J, 2011;52(2):114-8. PMID: 21483172.
- [pubmed] Sezai A, et al. "Carperitide and atrial fibrillation after coronary bypass grafting: the Nihon University working group study of low-dose HANP infusion therapy during cardiac surgery trial for postoperative atrial fibrillation." Circ Arrhythm Electrophysiol, 2015;8(3):546-53. PMID: 25840580.
- [pubmed] Takahashi R, et al. "Effects of continuous venovenous hemofiltration on the pharmacology of carperitide, a recombinant human atrial natriuretic peptide." Circ J, 2010;74(9):1888-94. PMID: 20668357.
- [pubmed] Gnädinger MP, et al. "Plasma kinetics of synthetic alpha-human atrial natriuretic peptide in man." Miner Electrolyte Metab, 1986;12(5-6):371-4. PMID: 2949138.
- [pubmed] Yandle TG, et al. "Metabolic clearance rate and plasma half life of alpha-human atrial natriuretic peptide in man." Life Sci, 1986;38(20):1827-33. PMID: 2939312.
- [pubmed] Torres-Courchoud I, et al. "B-type natriuretic peptide and acute heart failure: Fluid homeostasis, biomarker and therapeutics." Rev Clin Esp (Barc), 2016;216(7):393-398. PMID: 26961205.
- [fda] FDA. Drugs@FDA (openFDA): no application for carperitide. Read September 30, 2026.
- [other] European Medicines Agency. Medicines register (centrally authorised human medicines): no entry for carperitide. Read September 30, 2026.
Sources & Citations
Every study on this page was read from its PubMed record, including the 2016 review that records the 1995 Japanese approval. Regulatory status comes from FDA's Drugs@FDA database and EMA's register, read September 30, 2026. Grey Peptides sells nothing and links to no vendor.
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.