Effect of Clopidogrel on Early Inflammatory Response and In-Hospital Outcomes in Patients with Myocardial Infarction

Background: Inflammation plays a central role in the pathophysiology and clinical progression of acute myocardial infarction (MI). Although clopidogrel is known to exert potential anti-inflammatory effects in addition to platelet inhibition, the behavior of the early inflammatory response after treatment initiation and its prognostic significance remain unclear. This study aimed to evaluate dynamic inflammatory changes during the early post-treatment period and their association with in-hospital outcomes in patients with ST-elevation myocardial infarction. Methods: This retrospective, observational, single-center study included 300 patients with ST-elevation myocardial infarction treated with clopidogrel loading therapy. Systemic immune-inflammation index (SII), systemic inflammatory response index (SIRI), and delta neutrophil index (DNI) were evaluated before treatment and 24-48 h after therapy. In-hospital mortality and major adverse in-hospital outcomes were analyzed. Receiver operating characteristic analysis and multivariable logistic regression models were used to determine prognostic performance and independent predictors. Results: Contrary to the expected anti-inflammatory effect, all inflammatory markers significantly increased after clopidogrel therapy (all p < 0.05). Patients with persistent or increased inflammatory response demonstrated significantly higher rates of in-hospital mortality and major adverse outcomes. Post-treatment SIRI showed the strongest predictive performance for mortality (AUC: 0.81, 95% CI: 0.75-0.87), followed by ΔSIRI (AUC: 0.79). Multivariable analyses identified higher post-treatment inflammatory burden and dynamic inflammatory increases, particularly post-DNI and ΔSIRI, as independent predictors of mortality and adverse clinical course. Conclusions: Early inflammatory activation after clopidogrel therapy is strongly associated with poor in-hospital outcomes in patients with acute myocardial infarction. Persistent or increasing inflammatory burden may reflect an uncontrolled inflammatory response despite antiplatelet treatment and may serve as a practical and powerful prognostic marker for early risk stratification.