Carperitide
⚠ Approved in Japan only (1995). The Daiichi Sankyo recombinant hANP has been used in >30,000 pooled patients with acute heart failure in Japanese registries, but its overall mortality effect remains contested — 2024 meta-analyses suggest a possible increase in in-hospital mortality, while other pooled analyses suggest benefit at low doses.
Recombinant α-human atrial natriuretic peptide (α-hANP) — the 28-residue cardiac hormone secreted by atrial myocytes in response to atrial stretch — produced by chemical synthesis or recombinant methods. Approved in Japan since 1995 (Daiichi Sankyo) for acute heart failure. Never FDA-approved; no Western Phase 3 program. Acts via NPR-A / guanylate cyclase-A to produce vasodilation, natriuresis, and suppression of RAAS / SNS — the same receptor axis as nesiritide (which is recombinant BNP rather than ANP). Extensive Japanese real-world use: >30,000-patient pooled meta-analyses and multiple regional registries (COOPERATE-HF-J, REALITY-AHF, NARA-HF). 2024–2025 meta-analyses have raised concerns about increased in-hospital mortality versus placebo, while low-dose analyses (<0.02 μg/kg/min) have suggested benefit. No consensus; Japanese heart-failure guidelines (2019) continue to support selective use with acknowledged controversy.
Mechanism of action
Agonist at natriuretic peptide receptor A (NPR-A / GC-A), a membrane-bound guanylate cyclase. Receptor binding raises intracellular cGMP, producing arterial and venous vasodilation, natriuresis, and diuresis; suppression of renin, aldosterone, and sympathetic activity; and inhibition of cardiac hypertrophy and fibrosis pathways. Clinical hemodynamic profile in acute heart failure is reduction in pulmonary capillary wedge pressure and systemic vascular resistance, with modest increase in cardiac index. Mechanistically indistinguishable from nesiritide in terms of receptor engagement; slight differences in receptor affinity ratios between NPR-A and NPR-C (the clearance receptor) may account for minor pharmacologic differences, but the ANP / BNP distinction is primarily one of source peptide and regulatory history rather than mechanism.
Primary uses
- Acute heart failure (Japan-approved; used widely as adjunct to diuretics)
- Acute decompensated heart failure with volume overload (Japanese guideline-recommended)
Typical dosing
Japanese practice: 0.0125–0.025 μg/kg/min as low-dose (COOPERATE-HF-J pooled analysis). Higher doses (up to 0.1 μg/kg/min) have been associated with hypotension and increased in-hospital mortality in recent meta-analyses. ⚠ Not approved in the US; Japanese regulatory status only.
Regulatory status
Approved in Japan 1995 by Daiichi Sankyo for acute heart failure (regional PMDA approval). Never approved in the United States, European Union, United Kingdom, Canada, Australia, or Switzerland. No Western Phase 3 program was ever initiated; the FDA approval of nesiritide (recombinant BNP) in 2001 addressed a similar indication in the US market.
References
- [pubmed] Nogi K, Ueda T, Matsumoto T, et al. "Effect of carperitide on the 1-year prognosis of patients with acute decompensated heart failure." ESC Heart Fail, 2022;9(2):1135-1143.
- [pubmed] Honda S, Nagai T, Honda Y, 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.
- [review] Matsue Y, Kagiyama N, Yoshida K, et al. "Carperitide Is Associated With Increased In-Hospital Mortality in Acute Heart Failure: A Propensity Score-Matched Analysis." J Am Heart Assoc, 2015 (propensity-matched mortality signal).
Related peptides
This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.