Comparison of the clinical chemistry score to other biomarker algorithms for rapid rule-out of acute myocardial infarction and risk stratification in patients with suspected acute coronary syndrome

•Our study showcased several significant findings in evaluating the Clinical Chemistry Score (CCS) alongside other biomarker-based algorithms for acute myocardial infarction (AMI) rule-out and risk assessment. Here are the key highlights:•Diagnostic Evaluation: The CCS displayed reliable AMI rule-out capability with sensitivities and negative predictive values (NPVs) reaching 100% at CCS = 0. However, this led to a limited efficacy rate of 11.2%, while hs-cTnT alone at the limit of detection (LoD) (< 5 ng/L) demonstrated a higher efficacy of 18.4%. CCS ≤ 2 showed improved efficacy (55.7%), but hs-cTnT ≤14 ng/L exhibited a slightly higher efficacy rate (63.2%) with comparable NPVs.•Dual Marker Strategy (DMS): Utilizing hs-cTnT and copeptin, DMS demonstrated excellent sensitivity (95.8%) and NPV (98.9%) for AMI detection, surpassing CCS strategies in specificity and efficacy rates.•Combination with GRACE Score: Integrating GRACE risk scores with rule-out strategies enhanced diagnostic performance but consistently decreased efficacy rates. Only DMS combined with GRACE managed to match high NPVs of CCS ≤ 1 while maintaining a reasonable efficacy rate of 50.4% compared to CCS ≤ 1, which stood at 31.7%.•Prognostic Outcomes: CCS = 0 and the Limit of Blank (LoB) exhibited favorable short and long-term outcomes for all eligible patients at presentation. Yet, the CCS lacked superior performance in risk stratification compared to hs-cTnT-based strategies for AMI rule-out.•Study Insights and Limitations: Despite limitations like a single-center study, the research provides substantial insights into the diagnostic and prognostic performance of CCS, hs-cTnT, and copeptin. It offers valuable implications for patient management in emergency settings.•Conclusively, while the CCS demonstrates a reliable AMI rule-out in specific emergency department (ED) populations, its efficacy and specificity lag behind single or dual biomarker strategies using hs-cTnT. Future research should explore its performance in diverse populations and comparative analyses with other AMI biomarkers for improved diagnosis and risk assessment.