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PeptideAI
Approved drugcardiovascular

Carperitide

Recombinant atrial natriuretic peptide, approved only in Japan, infused to vasodilate and offload the heart in acute heart failure.

Also known as Hanp, recombinant human ANP, alpha-hANP, human atrial natriuretic peptide, Hanp

Approved drug — Licensed by a major regulator for human use, with phase-3 trial data behind it.

Approved in Japan since 1995 and used widely there, but the evidence base is mostly registry and observational data such as the ATTEND registry rather than large randomised outcome trials. Some of those analyses actually suggest worse outcomes in hypotensive patients. It has never been approved in the US or EU.

How it works

Carperitide is synthetic alpha-human ANP, identical to the peptide atrial myocytes release when atrial wall stretch increases. Like BNP it signals through the guanylyl cyclase-coupled NPR-A receptor, raising cGMP in vascular smooth muscle and in the renal collecting duct and inner medulla. The result is venodilatation that lowers preload, mild arterial dilatation that lowers afterload, direct natriuresis, and suppression of renin, aldosterone, sympathetic outflow and endothelin. Clearance is fast, via NPR-C-mediated internalisation and neprilysin, so the effect is fully titratable but disappears within minutes of stopping.

Targets: Natriuretic peptide receptor A (NPR-A), cGMP pathway, Renal collecting duct sodium handling

Dosing

ProtocolDoseFrequencyRoute
Acute decompensated heart failure (Japanese label protocol)Started on admission, commonly run for 24-72 hours.—continuous infusionintravenous
  • · Usual starting rate 0.1 mcg/kg/min, adjusted between roughly 0.025 and 0.2 mcg/kg/min by blood pressure and symptom response. Weight-based, so no fixed microgram dose applies.

Titration

Genuinely titrated in practice. Many Japanese centres start at 0.025-0.05 mcg/kg/min rather than the labelled 0.1 to reduce hypotension, then step up in 0.025 mcg/kg/min increments as blood pressure allows.

Cycling

An inpatient infusion for the acute episode, typically 1 to 3 days, not an ongoing therapy.

Work out your exact syringe units →

Pharmacology

Half-life
Very short, on the order of a few minutes; effects stop almost immediately when the infusion stops.
Onset
Haemodynamic effect within minutes of starting the infusion.
Routes
intravenous
Molecule
Recombinant 28-amino-acid atrial natriuretic peptide with a 17-residue disulfide ring
Sequence length
28 amino acids
Molecular weight
3080.5 Da

Handling

Diluent
Sterile water for injection, then diluted in 5% dextrose or saline
Typical mix
5 mL
Vial sizes
1 mg
Lyophilised
Store vials at room temperature per the Japanese label.
Reconstituted
Use promptly after reconstitution and dilution.

Mixing

Supplied as a 1000 mcg lyophilised vial reconstituted with 5 mL sterile water. Hospital pharmacy product; bacteriostatic water is not used.

Side effects

  • very commonHypotension— The rate-limiting effect and the main reason infusions are started below the labelled rate.
  • commonWorsening renal function— Driven largely by hypotension and reduced renal perfusion pressure.
  • commonElectrolyte disturbance— Natriuresis can pull sodium and potassium down.
  • commonHeadache and flushing
  • uncommonBradycardia

Do not use if

  • Cardiogenic shock or systolic blood pressure below roughly 90 mmHg.
  • Right ventricular infarction or other preload-dependent states.
  • Severe hypovolaemia or dehydration.
  • Known hypersensitivity to carperitide.

Combining it

  • cautionloop diuretics — Additive volume depletion and hypotension; the combination is common but needs close blood pressure watching.
  • redundantnesiritide — Same receptor, same effect - there is no reason to use both.
  • cautionACE inhibitors — Additive vasodilatation and hypotension.

What to monitor

  • · Continuous or very frequent blood pressure monitoring throughout the infusion.
  • · Serum creatinine, sodium and potassium daily.
  • · Urine output and fluid balance.
  • · Heart rate and rhythm.

Legal status

Approved prescription drug in Japan only. Not approved in the US or EU.

References

  • Hanp (carperitide) Japanese prescribing information (label)
  • Sato et al., ATTEND registry analyses of carperitide in acute heart failure (review)

Mechanism in depth

Carperitide is recombinant human atrial natriuretic peptide, the atrial rather than ventricular member of the family, acting on the same NPR-A guanylyl cyclase receptor as nesiritide and producing the same cGMP-mediated venodilation, arteriolar dilation, natriuresis and renin-aldosterone suppression. Two things distinguish it in practice. First, it is shorter-lived than BNP, so the infusion is even more of a real-time control knob and hypotension resolves faster once stopped. Second, and this is the substantive point, its evidence base is almost entirely Japanese registry and observational data rather than randomised outcome trials, and several of those analyses point the wrong way: in the ATTEND registry and related propensity-matched work, carperitide use in patients with lower blood pressure was associated with worse outcomes, and a 2025 meta-analysis of randomised and propensity-matched studies found no convincing outcome benefit. Mechanistically it does everything nesiritide does; clinically it inherits nesiritide's problem, which is that acute vasodilation in decompensated heart failure improves the afternoon and not the year.

What usually goes wrong

Hypotension in patients who were already marginal, and the registry data suggest that is not a benign event but the mechanism by which carperitide is associated with worse outcomes. The other thing that goes wrong is inertia: it is used widely in Japan because it has been used widely in Japan, on an evidence base that would not support approval anywhere else today. It has never been approved in the US or EU, and nothing sold outside Japan under this name is a regulated product.

Bloodwork worth running

MarkerWhenWhy it matters
Systolic blood pressureContinuously during infusion.The observational signal of harm concentrates in patients who were hypotensive to begin with. This is the single variable that separates reasonable use from harmful use.Act if: Systolic under about 100 mmHg is where the registry data turn against carperitide; do not start, and stop if pressure falls below 90 mmHg.
Serum creatinine and eGFRBaseline and daily.Excessive preload reduction plus hypotension is the mechanism by which a vasodilator worsens renal function in heart failure.Act if: A creatinine rise of 0.3 mg/dL or more with falling pressure means stop the infusion.
Serum sodium and potassiumDaily.Natriuresis on top of loop diuretics moves both, and carperitide is usually added to a patient already on furosemide.Act if: Sodium below 130 mmol/L should prompt reassessment of the whole diuretic and vasodilator strategy.
HaematocritDaily.A rising haematocrit during infusion is an early sign of intravascular volume depletion, which is what precedes the hypotension and renal injury.Act if: A rise of more than about 3 percentage points with falling blood pressure means over-decongestion.

Pharmacokinetics

Bioavailability
100%
Time to steady state
0.02 days
Crosses blood-brain barrier
no
Metabolism
Neprilysin cleaves the ring structure; NPR-C internalises and degrades intact peptide. ANP is intrinsically shorter-lived than BNP, which is why BNP became the drug of choice in the West.
Elimination
Enzymatic and receptor-mediated clearance; renal filtration is a minor route.

Receptor targets

  • NPR-A / particulate guanylyl cyclase A

    cGMP generation driving venodilation, arterial dilation, natriuresis and suppression of renin and aldosterone.

  • NPR-C clearance receptor

    Non-signalling clearance route; contributes to the very short circulating half-life.

Trials

  • ATTEND registry Prospective observational registry · n=4842 · 2013

    All-cause death and heart failure events in hospitalised acute heart failure patients in Japan. The registry is the main evidence base for carperitide in routine use and its analyses have generally not shown benefit, with signals of harm in hypotensive subgroups.

  • Shiga 2025 meta-analysis of randomised and propensity-matched carperitide studies Meta-analysis · 2025

    Pooled clinical outcomes with carperitide in acute heart failure. Did not establish an outcome benefit.

What to expect, and when

Haemodynamic effect within minutes of starting the infusion and essentially gone within 10 to 20 minutes of stopping. There is no tail; this is the most immediately controllable drug in the natriuretic peptide group.

Stacking and comparisons

Carperitide sits on top of loop diuretics in Japanese practice, and the combination is additively hypotensive and additively hypovolaemic. Adding nitrates or other vasodilators compounds that. Concurrent ACE inhibition, ARB or sacubitril/valsartan amplifies the cGMP effect; neprilysin inhibition specifically slows carperitide's own degradation. PDE5 inhibitors act downstream on the same second messenger and should not be combined.

Against nesiritide: same receptor, shorter half-life, tighter control, and a weaker evidence base, since nesiritide at least had a 7,141-patient randomised trial to fail. Against nitroglycerin: no demonstrated advantage and considerably more cost. Against cenderitide: cenderitide was explicitly designed to avoid carperitide's and nesiritide's hypotension problem by recruiting NPR-B as well.

Rough cost

Japanese hospital inpatient item; not sold in the US or EU and not a monthly-priced therapy. Cost analyses in Japan have argued it is a low-value expenditure.

Genuinely uncertain

  • The ATTEND registry participant number given here is the commonly cited enrolment for the cohort; I confirmed the registry and its publications but individual analyses use varying subsets.
  • Volume of distribution, clearance and protein binding for carperitide are not published in a form I could resolve, so those fields are null.
  • Japanese labelled dose ranges are quoted from general practice descriptions rather than a prescribing information document I retrieved in this session.

Papers