Predicting Clopidogrel Resistance in Acute Ischemic Stroke Patients: Key Clinical Insights and a Novel Diagnostic Nomogram

Background Clopidogrel plays an important role in the treatment of acute ischemic strokes (AIS) through antiplatelet activity. However, some patients have clopidogrel resistance (CR), which could lead to stroke recurrence and bleeding. This study aimed to explore associated factors of CR and establish a diagnostic nomogram for predicting the probability of CR in AIS patients. Methods This retrospective study involved 692 AIS patients from the Second Affiliated Hospital of Guangzhou Medical University, treated with clopidogrel (75 mg/day for 5 ± 2 days) after admission. Platelet reactivity was evaluated using thromboelastography to measure the ADP-induced platelet inhibition ratio (ADP-PIR). Patients were classified into CR (ADP-PIR < 30%) and non-clopidogrel resistance (NCR) groups. Group comparison, followed by least absolute shrinkage and selection operator (LASSO) regression and multivariable logistic regression, was used to identify key predictors of CR. A diagnostic nomogram was developed and its performance was validated using bootstrap resampling. Results 16.76% of 692 patients experienced CR after AIS. Beta blocker use (OR: 0.47, 95% CI: 0.22–1.03, P  = 0.058) and apolipoprotein A1 (OR: 0.17, 95% CI: 0.07–0.46, P  < 0.001) were protective, while unstable carotid plaque (OR: 10.65, 95% CI: 4.18–27.13, P  < 0.001), high apolipoprotein B levels (OR: 2.35, 95% CI: 1.23–4.51, P  = 0.01), and proton pump inhibitors use (OR: 2.09, 95% CI: 1.32–3.31, P  = 0.002) were risk factors. Our nomogram effectively validated these factors, showing strong discrimination and clinical utility in diagnosing CR probability. Conclusions We identified several significant CR predictors and further developed a diagnostic nomogram of CR to help clinicians choose antiplatelet drugs. Trial retrospectively registration: Trial Retrospectively registration = ChiCTR2300073944.Data: 2023-7-25. The present study was approved by the Ethics Committee of the Second Affiliated Hospital of Guangzhou Medical University.