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Heart failure represents a major health problem and economic burden also in development countries such as Indonesia. Based on current guidelines, the use of natriuretic peptides can improve diagnosis, risk stratification, and decrease in hospital length of stay. However, mostly due to the related high costs, many Indonesian physicians currently do not routinely use these biomarkers in their daily clinical practice. By comparing the results of guidance with N-terminal pro brain natriuretic peptide (NT-proBNP) and without NT-proBNP, this pilot study was aimed to determine the clinical effectiveness and costs of using natriuretic peptides in the management of acute heart failure (AHF) patients admitted at National Cardiovascular Center Harapan Kita Hospital, a tertiary referral hospital in Jakarta, Indonesia. This was a health economic evaluation using a single-blind, randomized controlled trial. AHF patients adjudicated following European Society of Cardiology guidelines were randomly assigned to the 2 groups: NT-proBNP group (group A) and control group (group B). In the group A, NT-proBNP level was obtained at admission and pre-discharge, with the target of achieving a decrease of ≥30%. Randomised patients were followed up to 90 days post-discharge to assess short-term outcomes and costs. In total, one hundred and twelve patients were enrolled, of whom 56 were randomized in group A and 56 patients in group B. Compared to Group B, in Group A the total costs of patients management resulted to be significantly higher (P<0.05), while no significant difference between the 2 groups was observed for inhospital length of stay, total mortality rate, rehospitalization, and emergency department visits within 90 days post-discharge. In this pilot study for the management of AHF at an Indonesian National Cardiovascular Center, the routine use of NT-proBNP compared to the non use, at hospital admission and discharge resulted into a significant increase of medical cost without any evident favourable impact on patients outcomes. Larger study in greater Asia Pacific populations should be performed to confirm these preliminary results.