Association of P2Y12 G52T genetic polymorphism with recurrent thromboembolic events in stroke and myocardial infarction patients on clopidogrel therapy: a prospective observational study

Cerebrovascular accidents like ischemic stroke and cardiovascular diseases together serve as the cause for 17.7 million deaths, in which Indians account for one-fifth of these cases. Around 4–30% of patients taking clopidogrel have no or reduced antiplatelet response. Clopidogrel response is influenced by genetic factors as well as non-genetic factors such as obesity, hypertension, diabetes mellitus, age, gender, social habits, and drug-drug interactions. This study evaluates the prevalence of P2Y12 and the association between P2Y12 polymorphism and clopidogrel therapy in recurrent stroke and myocardial infarction. A prospective observational study was carried out during November 2024 to June 2025, which included adults above 18 years with the diagnosis of stroke, TIA, MI, on single or dual antiplatelet therapy and excluded pregnant and lactating women as well as history of intracerebral haemorrhage, left ventricular (LV) clot, atrial fibrillation and cardiac embolism. Patients were classified into recurrent and non-recurrent groups based on the presence of recurrent ischemic events. Among the 100 participants who were recruited into the study, 62% of recurrent participants were between the ages of 55–75 years old. Among our cohort participants, the P2Y12 polymorphism showed no significant association with recurrent stroke. The etiological factors, hypertension was significantly associated in recurrent cases (p = 0.029), with longer duration of hypertension leading to recurrence (p = 0.001). Poor glycaemic control (GRBS > 200 mg/dL, 60% recurrent vs. 20% non-recurrent, p = 0.001) and smoking (p = 0.004) were other key risk factors. This study found that the P2Y12 polymorphism was not significantly associated with recurrent events in this study population, while hypertension, poor glycaemic control and smoking demonstrated statistically significant association. Further studies considering large and diverse cohorts with long-term follow-up, incorporating additional polymorphisms in association with recurrent events, may help with a positive outcome. This study emphasises the need to integrate genetic testing into clinical practice could help doctors tailor clopidogrel therapy to individual patients, improving treatment outcomes and reducing recurrent stroke and cardiovascular events.