ANP
Atrial natriuretic peptide (ANP), and carperitide as the recombinant form
Written by Aaron CuhaReviewed Sep 2026
Also known as: ANP, Atrial natriuretic peptide, alpha-hANP, Carperitide, Hanp
The hormone the heart releases when its chambers stretch, and the reason the heart counts as an endocrine organ. Its recombinant form, carperitide, is used for acute heart failure in Japan; a 2025 meta-analysis of 9 studies found higher in-hospital mortality in carperitide-treated patients when randomised and propensity-matched studies were pooled.
Overview
Atrial natriuretic peptide is a 28 amino acid peptide, sequence SLRRSSCFGGRMDRIGAQSGLGCNSFRY, released from atrial cells when the chamber wall is stretched. It makes the kidney excrete sodium and water, relaxes blood vessels and opposes the renin-angiotensin system. One important detail for anyone reading about it: ANP names a family of fragments from one precursor, which also yields urodilatin, vessel dilator, kaliuretic peptide and long-acting natriuretic peptide. They are not the same molecule and they are not interchangeable.
The human evidence for giving it as a drug comes almost entirely from Japan, where a recombinant form called carperitide is used intravenously in acute heart failure. That evidence does not point the way the mechanism suggests. A propensity score-matched analysis of 367 matched pairs found carperitide associated with higher in-hospital mortality, odds ratio 2.13, 95 percent confidence interval 1.17 to 3.85. A 2025 meta-analysis of 9 studies, 4 randomised and 5 propensity-matched, found pooled in-hospital mortality higher with carperitide, odds ratio 1.38, 95 percent confidence interval 1.07 to 1.78, while the 4 randomised trials analysed alone showed no significant difference with a confidence interval so wide it excluded almost nothing. A pooled Japanese cohort analysis of 2,435 patients pointed the other way, with lower 1 year mortality in the low-dose group. Those results are in conflict and the page reports them as such.
Regulatory position, checked 11 September 2026: no ANP or carperitide product appears in Drugs@FDA. Carperitide's Japanese approval is described consistently in the clinical literature, including a 2025 meta-analysis that states it is used intravenously for acute heart failure primarily in Japan, but this site did not verify a PMDA record directly and does not assert the approval date or terms.
Mechanism of action
In humans, ANP binds NPR-A (gene NPR1), a particulate guanylyl cyclase, raising cyclic GMP in vascular smooth muscle and kidney tubule cells. The results are natriuresis, diuresis and vasodilation, plus suppression of renin and aldosterone. It is cleared by the NPR-C receptor and degraded by neprilysin, which is why neprilysin inhibition (the sacubitril half of sacubitril/valsartan) raises natriuretic peptide concentrations rather than supplying them. Human dosing data show the diuretic response varies a great deal between patients: in 75 people with acute heart failure, lower baseline ANP and lower vasopressin predicted a larger diuretic response to infused carperitide.
Human evidence
Substantial human dosing experience exists, almost all of it Japanese and almost all of it observational. Randomised evidence is small: the trials pooled in the 2025 meta-analysis were too small and too few to settle mortality, and the one head to head randomised comparison against tolvaptan favoured tolvaptan on adverse events.
- Meta-analysis of 9 studies (2025): pooled in-hospital mortality odds ratio 1.38, 95 percent confidence interval 1.07 to 1.78 across randomised and propensity-matched studies together; the randomised studies alone were uninformative (odds ratio 0.85, confidence interval 0.07 to 10.49).
- Propensity-matched cohort (2015): 367 matched pairs, in-hospital mortality odds ratio 2.13, 95 percent confidence interval 1.17 to 3.85.
- Pooled Japanese cohorts (2022): 2,435 patients; lower 1 year cardiovascular and all-cause mortality in the low-dose carperitide group than in the no-carperitide group, which contradicts the in-hospital analyses above.
- AVCMA randomised trial (2013): 109 patients, carperitide versus tolvaptan. Similar symptom and BNP improvement; more adverse events requiring discontinuation with carperitide (p = 0.027).
- Electrolyte and diuretic physiology in people: 162 patients showed a modest fall in potassium with no change in sodium; 75 patients showed that baseline ANP and vasopressin concentrations predict who responds.
What this does not tell you: No randomised trial has shown that carperitide or any ANP preparation reduces mortality, and the observational signals contradict each other in direction. Everything comes from acute heart failure in hospital, mostly in Japan, mostly with short infusions. Nothing here says anything about ANP for blood pressure, kidney protection or longevity in people who are not acutely unwell, and no product exists outside that setting.
Reading the research record
ANP is the reason the heart is described as an endocrine organ, and that discovery has been far more useful as a diagnostic and as a drug target than as a drug. Measuring natriuretic peptides is now routine in heart failure, and the most successful modern heart failure drug works by blocking neprilysin, the enzyme that destroys them, rather than by injecting them.
The carperitide record shows why that distinction matters. Japanese practice adopted the infusion widely on physiological grounds, and the outcome evidence that followed was observational and conflicting: propensity-matched analyses showing more in-hospital deaths, a pooled cohort analysis showing fewer deaths at 1 year in the low-dose group, and randomised trials too small to arbitrate. The 2025 meta-analysis is explicit that clinical effectiveness has not been established. The parallel with nesiritide, the B-type natriuretic peptide that was approved in the United States and is now discontinued, is close enough that both pages should be read together.
One stated limitation of this page: the Japanese regulatory status of carperitide is reported here only as the clinical literature describes it, because no regulator record was checked directly. The research file behind this page flags that explicitly and it is not papered over.
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 6 distinct years, 2013 to 2025, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Approved
AU
Approved
CA
Not approved
Approved in 2 of 4, prescription route in 0, not approved in 2. 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
- Human2025
Effect of carperitide on clinical outcomes among patients with acute heart failure: a meta-analysis of randomized and propensity-matched studies
9 studies, 4 randomised and 5 propensity score-matched. Pooled in-hospital mortality was higher with carperitide, odds ratio 1.38, 95 percent confidence interval 1.07 to 1.78, with high heterogeneity (I squared 77 percent). The 4 randomised trials alone gave odds ratio 0.85 with a 95 percent confidence interval of 0.07 to 10.49, which is uninformative. No significant difference in long-term mortality, rehospitalisation, hypotension or length of stay.
BMC Cardiovascular Disorders - Human2015
Carperitide Is Associated With Increased In-Hospital Mortality in Acute Heart Failure: A Propensity Score-Matched Analysis
Retrospective multicentre cohort, 402 of the patients treated with carperitide, 367 matched pairs analysed. Carperitide was associated with in-hospital mortality, odds ratio 2.13, 95 percent confidence interval 1.17 to 3.85, with a larger association in older patients (odds ratio 2.93, 1.54 to 5.91). Observational, so treatment choice and severity cannot be separated.
Journal of Cardiac Failure - Human2022
Effect of carperitide on the 1 year prognosis of patients with acute decompensated heart failure
Pooled analysis of two Japanese cohorts, 2,435 patients with acute decompensated heart failure split by carperitide dose. Cardiovascular and all-cause mortality within 1 year were lower in the low-dose group (at or above 0.02 micrograms per kilogram per minute) than in the no-carperitide and very-low-dose groups. This observational result points in the opposite direction to the propensity-matched in-hospital analyses and is reported here alongside them, not instead of them.
ESC Heart Failure - Human2013
Acute heart failure volume control multicenter randomized (AVCMA) trial: comparison of tolvaptan and carperitide
109 hospitalised patients randomised to tolvaptan or carperitide. Symptoms and plasma BNP improved similarly in both groups. Blood pressure was lower after carperitide, and fewer adverse events such as worsening heart failure and hypotension requiring discontinuation occurred with tolvaptan (p = 0.027).
Journal of Clinical Pharmacology - Human2021
Moderate potassium lowering effect of exogenous atrial natriuretic peptide in patients with acute heart failure
Post-hoc analysis of a multicentre prospective cohort, 162 patients with acute heart failure given intravenous carperitide. Serum sodium was unchanged over 48 hours; serum potassium fell from 4.32 to 4.08 mEq/L with carperitide alone (p = 0.004). Hypokalaemia at 24 hours was uncommon unless 20 mg or more of furosemide was added (12.5 versus 2.8 percent, p = 0.039).
Journal of Cardiology - Human2022
Neuroendocrine hormone status and diuretic response to atrial natriuretic peptide in patients with acute heart failure
75 patients with acute heart failure given 0.0125 micrograms per kilogram per minute of carperitide for 6 hours. Lower baseline plasma ANP (r = -0.35, p = 0.002) and lower vasopressin (r = -0.54, p < 0.001) predicted a larger diuretic response; baseline blood pressure, renal function and prior loop diuretic use did not.
ESC Heart Failure - Review2019
Atrial Natriuretic Peptide, Heart Failure and the Heart as an Endocrine Organ
Physiology review covering the discovery of ANP, the precursor-derived family of fragments, NPR-A signalling and clearance by NPR-C and neprilysin. NIH supported.
Clinical Chemistry
Frequently asked questions
Is ANP available as a drug?
Not in the United States. No ANP or carperitide product appeared in the Drugs@FDA query on 11 September 2026. A recombinant form, carperitide, is described in the clinical literature as in use for acute heart failure in Japan, and this site did not verify that with the Japanese regulator.
Does carperitide help people with acute heart failure?
The evidence does not establish that it does. A 2025 meta-analysis of 9 studies found higher pooled in-hospital mortality with carperitide, odds ratio 1.38, while the randomised trials alone were too small to say anything. A separate pooled Japanese cohort of 2,435 patients found lower 1 year mortality in the low-dose group. Those results conflict, and none of them is a large randomised outcome trial.
Is ANP the same as BNP or NT-proBNP?
No. ANP comes from the atria and its precursor also yields urodilatin and several other fragments. BNP comes from a different gene and its inactive fragment NT-proBNP is the blood test used in heart failure. They act on the same receptor, NPR-A, but they are different molecules with different clinical uses.
Can ANP be taken for blood pressure or kidney health?
No. There is no oral form, no approved product outside Japanese hospital practice, and no human study of ANP in people who are not acutely unwell. Everything published is short intravenous dosing in acute heart failure.