BACKGROUND: Acute myocardial infarction (AMI) significantly contributes to the progression of heart failure (HF). Standard treatment for HF has long been angiotensin-converting enzyme inhibitors (ACEIs), targeting the renin-angiotensin-aldosterone system (RAAS). Recent developments in HF management introduced sacubitril/valsartan (S/V), a novel angiotensin receptor-neprilysin inhibitor (ARNI), showing promising results in global trials. This study aimed to assess the efficacy of early S/V application compared to angiotensin-converting enzyme inhibitors (ACEIs) in reducing NT-proBNP levels and improving clinical outcomes, specifically focusing on dyspnea symptomatology, in Chinese patients with AMI complicated by HF. METHODS: This single-center, mixed methods study was conducted at Tangshan Gongren Hospital from January to December 2021, including 88 patients diagnosed with AMI and HF. Patients were divided into two groups: 31 received S/V, while 57 were treated with ACEIs. Data collection encompassed baseline demographic, clinical, and biochemical variables, NT-proBNP levels, blood pressure measurements, and dyspnea symptom severity. Follow-up assessments were conducted 1 year post-discharge to evaluate NT-proBNP levels, and symptom progression. Statistical analyses, including t-tests, Wilcoxon rank-sum tests, and chi-square tests, were performed to compare outcomes between the two groups. RESULTS: At baseline, no significant differences were observed between the two groups in terms of demographic, lifestyle, and medical history. Although patients in the S/V group presented with more severe baseline renal impairment and cardiac dysfunction, there was no significant difference in NT-proBNP levels from admission to discharge. 1-year follow-up showed a trend towards reduced NT-proBNP levels in the S/V group, though this difference did not reach statistical significance. All patients in both groups reported improvements in dyspnea at discharge and at follow-up, with no significant inter-group difference. Notably, the S/V group demonstrated a more significant reduction in both systolic and diastolic blood pressure from admission to discharge compared to the ACEIs group. CONCLUSIONS: This study found that S/V had similar effects to ACEIs in reducing NT-proBNP levels among Chinese patients with AMI complicated by HF, though S/V was associated with greater reductions in blood pressure. These findings suggest that while S/V may offer additional benefits in blood pressure management, its impact on cardiac biomarkers in acute settings may not significantly differ from ACEIs. Given the study's limitations, including its single-center design, small sample size, and baseline differences. Further multi-center, randomized controlled trials are warranted to validate these findings and explore tailored treatment strategies for AMI patients with concurrent HF.