Carperitide (ANP)

Recombinant human alpha-atrial natriuretic peptide of 28 amino acids, approved in Japan in 1995 as Hanp for acute heart failure, where it is widely infused as a vasodilator and diuretic without a demonstrated mortality benefit.

Also referenced as: Hanp, alpha-hANP, ANP 1-28, Carperitide (genetical recombination)

Also appears in: Hormone

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What is Carperitide (ANP)?

Carperitide is the recombinant form of alpha-human atrial natriuretic polypeptide (alpha-hANP), the 28-amino-acid hormone that cardiac atria release in response to stretch. Kangawa and Matsuo isolated it from human atrial extract in 1984, showed potent diuretic, natriuretic and vasorelaxant activity in rats, and established the complete sequence (Kangawa and Matsuo, Biochemical and Biophysical Research Communications, 1984;118(1):131–139). The sequence is Ser-Leu-Arg-Arg-Ser-Ser-Cys-Phe-Gly-Gly-Arg-Met-Asp-Arg-Ile-Gly-Ala-Gln-Ser-Gly-Leu-Gly-Cys-Asn-Ser-Phe-Arg-Tyr with a disulfide bridge between cysteines 7 and 23 that closes the 17-residue ring shared by all natriuretic peptides; the molecular formula is C127H203N45O39S3 and the molecular weight about 3,080 Da. Carperitide is the USAN and INN; the Japanese Accepted Name is carperitide (genetical recombination), reflecting production in Escherichia coli, and the brand is Hanp.

Developed by Suntory and marketed in Japan since May 1995 for acute heart failure, it is held today by Daiichi Sankyo under approval number 20700AMZ00027. It is the atrial counterpart of nesiritide, the recombinant B-type natriuretic peptide approved in the US in 2001 and whose approval was withdrawn in 2020, and is distinct from anaritide, a 25-residue synthetic ANP fragment that failed US renal trials. Carperitide has no approval outside Japan.

How it works

• Agonist at guanylyl cyclase-A (NPR1). ANP binds the extracellular domain of the single-pass receptor guanylyl cyclase-A; the crystal structure of the hormone-bound dimerized domain shows that binding twists the two monomers, rotating the juxtamembrane regions by 24 degrees and switching on the intracellular cyclase, which raises cGMP (Ogawa et al., Journal of Biological Chemistry, 2004;279(27):28625–28631). Mice lacking the receptor develop chronic, salt-resistant hypertension with unchanged ANP and aldosterone concentrations (Lopez et al., Nature, 1995;378(6552):65–68). The Japanese label lists vasodilation, diuresis and inhibition of renin and aldosterone secretion as the downstream effects.
• Hemodynamic unloading and natriuresis in heart failure. In the first clinical infusions of synthetic alpha-hANP in patients with class III or IV heart failure, the peptide lowered pulmonary capillary wedge pressure and systemic resistance, increased stroke volume index, tended to raise urine volume, sodium excretion and creatinine clearance, and lowered plasma aldosterone, an improvement attributed mainly to vasodilation (Saito et al., Circulation, 1987;76(1):115–124).
• Very short half-life and dual clearance. Natriuretic peptides are removed by the clearance receptor NPR-C, which internalizes and degrades them without signaling, and by the membrane peptidase neprilysin (Potter et al., Endocrine Reviews, 2006;27(1):47–72). The label reports alpha and beta half-lives of 2.8 and 25.3 minutes during infusion in 10 patients with acute heart failure, a clearance of 91.4 mL/min/kg after a bolus in six healthy men, and roughly 0.001% of a dose recovered unchanged in urine.
• Proposed cardioprotection. The J-WIND investigators argued that ANP infused during reperfusion limits reperfusion injury and later remodeling through cGMP-dependent signaling in cardiomyocytes and the microvasculature (Asakura and Kitakaze, Cardiovascular Drugs and Therapy, 2010;24(3):289–295).

Research status

Japanese approval and post-marketing experience. The Hanp label summarizes the domestic program, including a double-blind trial, in which hemodynamic improvement was recorded in 102 of 155 patients (65.8%) and overall improvement in 80 of 125 (64.0%). A six-year prospective post-marketing registry followed 3,777 patients with acute heart failure (median age 73): 82% were judged clinically improved, response was poorer in acute myocardial infarction, Killip class IV and renal impairment, adverse events occurred in 16.9%, blood pressure lowering in 9.5%, and 7-day mortality was 11.4% (Suwa et al., Circulation Journal, 2005;69(3):283–290). The ATTEND registry of 4,842 hospitalized patients found carperitide among the most commonly used in-hospital drugs and called for its benefit to be clarified (Sato et al., Circulation Journal, 2013;77(4):944–951).

PROTECT. The first randomized outcome study assigned 49 patients with acute decompensated heart failure to a 72-hour low-dose infusion or standard care; death or rehospitalization over 18 months occurred in 11.5% versus 34.8% (P=0.0359) (Hata et al., Circulation Journal, 2008;72(11):1787–1793). A later phase 4 trial in patients with combined cardiac and renal failure, started in May 2009, was terminated without posted results (NCT00613964).

J-WIND in acute myocardial infarction. In a single-blind trial at 65 Japanese hospitals, 277 patients undergoing reperfusion were assigned to a 3-day ANP infusion and 292 to placebo. Infarct size estimated from creatine kinase release was 14.7% smaller (95% CI 3.0 to 24.9%; P=0.016) and ejection fraction at 6 to 12 months was higher (ratio 1.05, 95% CI 1.01 to 1.10; P=0.024), but severe hypotension occurred in 29 ANP patients against 1 on placebo (Kitakaze et al., Lancet, 2007;370(9597):1483–1493). Carperitide carries no myocardial infarction indication.

Cardiac surgery. In a Nihon University series, 303 patients with chronic kidney disease, postoperative creatinine was lower with carperitide through the first year, with fewer cardiac events and dialysis starts but no difference in mortality (Sezai et al., Journal of the American College of Cardiology, 2011;58(9):897–903), and in 668 patients randomized to carperitide or saline from the start of cardiopulmonary bypass, postoperative atrial fibrillation occurred in 12.2% versus 32.7% (P<0.0001) (Sezai et al., Circulation: Arrhythmia and Electrophysiology, 2015;8(3):546–553). A meta-analysis of 15 surgical trials of carperitide or nesiritide found lower peak creatinine, arrhythmia and renal replacement therapy with ANP (Mitaka et al., Critical Care, 2011;15(5):R258), and a meta-analysis of 18 randomized trials of low-dose ANP found a halving of new acute kidney injury (RR 0.51, 95% CI 0.36 to 0.72) while concluding that sample sizes and quality were insufficient to establish efficacy (Yamada et al., Critical Care, 2019;23(1):41).

Observational outcome data. A single-center propensity analysis of 879 admissions found that an unadjusted mortality advantage disappeared after matching (4.0% versus 5.1%; P=0.609) (Ogiso et al., Heart and Vessels, 2017;32(8):916–925). In the nationwide JROAD-DPC claims database, 45,595 patients given carperitide or nitrates as first-line vasodilators in 808 hospitals were compared after inverse probability weighting; carperitide was associated with higher in-hospital mortality (HR 1.49, 95% CI 1.35 to 1.64) and longer stays (Nagai et al., International Journal of Cardiology, 2019;280:104–109). A pooled analysis of 2,435 patients found lower 1-year cardiovascular mortality with doses of 0.02 µg/kg/min or more (HR 0.696, 95% CI 0.513 to 0.944) but not with lower doses (Nogi et al., ESC Heart Failure, 2022;9(2):1061–1070).

LASCAR-AHF. The randomized test of the low-dose hypothesis enrolled 247 patients with acute heart failure at nine Japanese sites between November 2014 and March 2021. All-cause death or heart failure hospitalization within 2 years occurred in 36 of 122 (29.5%) with carperitide versus 35 of 125 (28.0%) with standard treatment alone (HR 1.26, 95% CI 0.78 to 2.06; P=0.827), with a larger fall in estimated glomerular filtration rate with carperitide (difference −3.9 mL/min/1.73 m2, 95% CI −7.0 to −0.8). Enrollment was stopped early, leaving the trial underpowered (Honda et al., European Heart Journal: Acute Cardiovascular Care, 2025;14(2):83–92).

2025 meta-analyses. Pooling four randomized and five propensity-matched studies, in-hospital mortality was higher with carperitide overall (OR 1.38, 95% CI 1.07 to 1.78) but not in the randomized trials alone (OR 0.85, 95% CI 0.07 to 10.49) (Shiga et al., BMC Cardiovascular Disorders, 2025;25(1):896). A second analysis of six studies and 30,665 patients found no effect on heart failure mortality (RR 0.81, 95% CI 0.45 to 1.45) and higher in-hospital mortality (RR 1.16, 95% CI 1.07 to 1.27) (Khan et al., American Heart Journal Plus, 2025;59:100624).

Guidelines. The JCS 2017/JHFS 2017 guideline describes carperitide as indicated for pulmonary congestion in acute heart failure and used with catecholamines or other inotropes in refractory heart failure, notes hypotension at the start of treatment, and states that, like other vasodilators, it has not been shown to improve prognosis (Tsutsui et al., Circulation Journal, 2019;83(10):2084–2184). The 2023 trilateral statement of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society covers carperitide alongside nesiritide and angiotensin receptor neprilysin inhibitors as the therapeutic uses of natriuretic peptides (Tsutsui et al., Journal of Cardiac Failure, 2023;29(5):787–804).

US program. Suntory Pharmaceutical ran a phase 2 placebo-controlled dose-ranging trial in acute respiratory distress syndrome from December 1999 (NCT00030121), listed as completed with no results posted. Daiichi Sankyo ran a phase 2 pharmacokinetic and hemodynamic dose-escalation study in 162 patients with congestive heart failure at US and Canadian sites from January 2004 to February 2006 (NCT00259038), also listed as completed without posted results. No US-directed development has been registered since that study. Drugs@FDA and DailyMed list no carperitide application or label, and as of November 2026 no US-directed program exists. The related fragment anaritide failed to improve dialysis-free survival in 504 patients with acute tubular necrosis (Allgren et al., New England Journal of Medicine, 1997;336(12):828–834).

Common dosage forms

• Hanp Injection 1000. A lyophilized powder in single-dose vials containing 1,000 µg of carperitide (genetical recombination), supplied in packs of 10 vials by Daiichi Sankyo and administered intravenously by hospital staff.
• No other presentation. The vials used in the US phase 2 trials were never marketed, no oral, subcutaneous or nasal form exists, and no product is approved outside Japan.

Key considerations

• Regulatory status. The Research Market status reflects the absence of any FDA-approved carperitide product. Drugs@FDA and DailyMed list no carperitide application or label as of November 2026, and no US-directed program is registered. Carperitide is approved in Japan as Hanp (approval number 20700AMZ00027, marketed since May 1995) for acute heart failure, including acute exacerbations of chronic heart failure.
• Symptom relief without an outcome signal. Three decades of Japanese use rest on hemodynamic and symptomatic improvement; the only randomized outcome trials are the 49-patient PROTECT study and the underpowered LASCAR-AHF, which found no reduction in death or rehospitalization, and both 2025 meta-analyses associate carperitide with higher in-hospital mortality in pooled observational data.
• Hypotension is the dominant risk. J-WIND recorded severe hypotension in 29 ANP patients against 1 on placebo, the post-marketing registry recorded blood-pressure lowering in 9.5% of 3,777 patients, and LASCAR-AHF found a larger fall in glomerular filtration rate with carperitide despite its low dose.
• Perioperative findings are unconfirmed. The large reductions in postoperative atrial fibrillation and dialysis come mainly from one Japanese surgical center, and the 2019 meta-analysis judged the pooled acute kidney injury trials too small to settle the question.
• Naming. Carperitide, alpha-hANP, ANP 1-28 and Hanp denote the same 28-residue peptide. It is not interchangeable with nesiritide, which is B-type natriuretic peptide, or with anaritide, the 25-residue ANP fragment tested in US renal trials.