Effect of carperitide on the 1 year prognosis of patients with acute decompensated heart failure

Abstract

AimsAcute heart failure (AHF) is a clinical syndrome with a poor prognosis and a major public health concern worldwide. The aim of this study was to investigate whether carperitide administration improves the 1 year prognosis of patients with AHF and to check whether there is an optimal dose of the drug.Methods and resultsWe analysed the data of COOPERATE‐HF‐J (the Consortium for Pooled Data Analysis regarding Hospitalized Patients with Heart Failure in Japan), combining two cohorts (NARA‐HF and REALITY‐AHF), which included 2435 patients with acute decompensated heart failure. The patients were divided into no carperitide (NO‐ANP, n = 1098); very low‐dose carperitide (VLD‐ANP, <0.02 μg/kg/min, n = 593); and low‐dose carperitide groups (LD‐ANP, ≥0.02 μg/kg/min, n = 744). The primary endpoint was cardiovascular mortality within 1 year after admission. The secondary endpoints were all‐cause mortality and rehospitalization due to worsening heart failure within 1 year after admission. The median carperitide doses in the VLD‐ANP and LD‐ANP groups were 0.013 and 0.025 μg/kg/min, respectively. Kaplan–Meier analysis showed that cardiovascular mortality and all‐cause mortality were significantly lower in the LD‐ANP group than in the NO‐ANP and VLD‐ANP groups (P < 0.001 and P = 0.002, respectively). Multivariable Cox regression analysis for cardiovascular and all‐cause mortality revealed that LD‐ANP was significantly associated with lower cardiovascular and all‐cause mortality within 1 year after admission, even after adjusting other covariates (hazard ratio: 0.696 and 0.791, 95% confidence interval: 0.513–0.944 and 0.628–0.997, P = 0.020 and 0.047, respectively).ConclusionsLow‐dose carperitide was significantly associated with lower cardiovascular and all‐cause mortality within 1 year after admission. Our results suggest the necessity for well‐designed randomized controlled trials to determine the doses of carperitide that could improve clinical outcomes in patients with AHF.

Natriuretic peptide pathways in heart failure: further therapeutic possibilities

“… 61 , 62 Indeed, for over two decades, the use of low-dose ANP (carperitide) for ADHF, at non-hypotensive doses, has demonstrated overall efficacy and safety when administered often over 72 h. Nogi et al . 74 recently reported that low-dose carperitide in ADHF was associated with lower cardiovascular and all-cause mortality within 1 year after admission. The use of recombinant BNP (nesiritide) in ADHF in early studies demonstrated improved symptoms and haemodynamic unloading of the heart, yet hypotensive dosing often was associated with worsening renal perfusion and impaired renal function, resulting in limited use of nesiritide.…”

Natriuretic peptides: role in the diagnosis and management of heart failure: a scientific statement from the Heart Failure Association of the European Society of Cardiology, Heart Failure Society of America and Japanese Heart Failure Society

“…86 Also, plasma atrial natriuretic peptide levels increased after ARNI administration. 79 In PROVE-HF, changes in plasma NT-proBNP levels were significantly correlated with changes in LV and left atrial volumes, LVEF and parameters of diastolic function, showing their value as predictors of the changes in cardiac function in addition to outcomes. 88 NT-proBNP plasma levels are excellent prognostic makers in patients with HF receiving ARNIs.…”

“…However, in a recent report using the Japanese registry database, authors demonstrated that carperitide was related to worse outcomes when compared to nitrates 78 . In contrast, the consortium for pooled data analysis regarding hospitalized patients with HF in Japan, the COOPERATE‐HF‐J (Consortium for Pooled Data Analysis regarding Hospitalized Patients with Heart Failure in Japan) study, revealed that carperitide improved the prognosis of patients with acute HF 79 . These study findings suggest that blood pressure and renal function may influence the efficacy of carperitide 80 .…”

CNP, the Third Natriuretic Peptide: Its Biology and Significance to the Cardiovascular System

“…ANP and BNP are mainly synthesized in the heart. Currently, ANP is widely used in the treatment of acute heart failure in Japan [ 5 , 6 , 7 ], while BNP is used as a biomarker of heart failure worldwide [ 8 , 9 , 10 ]. CNP, by contrast, is widely expressed in the central nervous system, osteochondral system, and vascular system, and the receptor mainly targeted by CNP differs from that targeted by ANP and BNP.…”