Precision Medicine in Acute Coronary Syndromes: Integrating Plaque Phenotyping, Personalized Revascularization, Antithrombotic Strategies, and Residual Risk Reduction

Acute coronary syndromes (ACS) are biologically and clinically heterogeneous, with substantial variation in mechanisms of coronary instability, coronary anatomy, ischemic and bleeding risk, and residual cardiovascular risk. Although advances in imaging, risk stratification, and targeted therapies have expanded opportunities for individualized care, their clinical actionability remains uneven. This narrative review proposes a longitudinal precision-medicine framework integrating four interconnected domains—mechanism, anatomy, ischemic–bleeding risk, and residual biological risk—to examine how patient characterization can inform treatment selection and reassessment. Contemporary evidence on mechanistic phenotyping, coronary imaging, revascularization, antithrombotic therapy, and residual cardiovascular risk is critically synthesized, with particular emphasis on distinguishing strategies supported by randomized clinical-outcome evidence from those supported primarily by mechanistic, imaging, biomarker, or other surrogate endpoints. Mechanistic and imaging-based characterization can refine ACS phenotyping, while coronary anatomy and clinical characteristics inform revascularization decisions. Dynamic assessment of ischemic and bleeding risk supports individualized antithrombotic strategies, and lipid-related, inflammatory, thrombotic, and cardiometabolic phenotypes inform residual-risk assessment and secondary prevention. However, the evidence supporting phenotype-guided treatment remains heterogeneous. Several anatomy- and risk-informed strategies have demonstrated clinical benefit, whereas morphology-guided intervention, biomarker-directed treatment, molecular phenotyping, and artificial-intelligence-assisted decision support require further validation before routine implementation. The proposed framework distinguishes clinically actionable information from findings that remain primarily prognostic or hypothesis-generating. Diagnostic precision currently exceeds therapeutic precision in several areas of ACS care. A longitudinal framework integrating mechanism, anatomy, ischemic–bleeding risk, and residual biological risk may help connect patient phenotyping to evidence-based treatment decisions, identify where treatment-effect evidence remains insufficient, and support reassessment as clinical and biological risk evolves. Precision ACS care should therefore prioritize demonstrated clinical benefit rather than diagnostic sophistication alone.