Abstract Body: INTRODUCTION
Cerebrovascular and cardiovascular diseases are major causes of global mortality, with significant impact in India. Clopidogrel, an antiplatelet prodrug, requires activation by CYP enzymes to inhibit platelet activation. Clopidogrel resistance, affecting 4-30% of patients, is often due to CYP2C19 gene variations, among other factors. This study explores genetic variants associated with clopidogrel resistance to improve personalized therapy for thrombotic conditions.
OBJECTIVE
To evaluate the relationship between CYP2C19 polymorphisms and recurrent thrombotic events in patients treated with clopidogrel for coronary artery disease and stroke.
METHODS
An ambispective observational study at a tertiary hospital over six months included 114 adults on clopidogrel for various ischemic conditions. Exclusion criteria were pregnancy, lactation, intracerebral hemorrhage, atrial fibrillation, left ventricular clot, and cardioembolic stroke. Data were collected from medical records. CYP2C192 and CYP2C193 polymorphisms were analyzed using PCR and gel electrophoresis. Statistical analysis was conducted with chi-square tests in IBM SPSS version 20.0 (p<0.05).
RESULTS
The study included 114 participants (71.9% males, mean age 64.7 ± 10.9 years). Significant associations were found between recurrent ischemic events and hypertension (p=0.001), diabetes (p=0.033), and smoking (p=0.001). Of the 114 patients, 72 (63.2%) were positive for CYP2C19*2, with 61 (84.7%) experiencing recurrent events (p=0.005). CYP2C19*3 positivity was observed in 20 (17.5%) patients, with 9 (45%) having recurrent events (p=0.401). All 12 patients who underwent PCI had recurrent thrombotic events (p=0.000), with 7 (58.3%) having CYP2C19 polymorphisms—5 with CYP2C19*2 and 2 with CYP2C19*3. Medication adherence was not significantly linked to recurrence (p=0.063). The findings suggest a potential association between CYP2C19*2 and recurrent thrombotic events.
CONCLUSION
This study highlights a significant association between CYP2C192 polymorphism and recurrent thrombotic events in clopidogrel-treated patients, indicating that genetic screening may help identify clopidogrel resistance. No significant association was found with CYP2C193. Smoking, hypertension, and diabetes were significant risk factors for recurrent ischemic events. The high prevalence of CYP2C19 polymorphisms among PCI patients with recurrent thrombotic events suggests the potential benefit of genetic screening in clinical practice.