Single nucleotide polymorphism of CYP3A5*3 contributes to clopidogrel resistance in coronary artery disease patients among Tamilian population
BACKGROUND Clopidogrel has become the standard antiplatelet drug along with aspirin in patients undergoing coronary angioplasty; however, data regarding the nonresponse rate to clopidogrel therapy in Indian patients are limited. METHODS AND RESULTS Platelet aggregation was measured at baseline and 2 and 24 hours post administration of bolus dose of 300 mg clopidogrel, followed by 75 mg once daily in patients undergoing elective or adhoc coronary angioplasty. Baseline platelet aggregation with 2.5 and 10 micromol/L ADP was 27.91 +/- 20.9% and 53.45 +/- 22.44%. Platelet aggregation at 2 hours and 24 hours with 2.5 micromol/L of ADP was 19.65 +/- 16.9% and 10.44 +/- 11.9%. The corresponding values with 10 micromol of ADP were 48.81 +/- 25.3% and 27.04 +/- 22.4%. Platelet aggregation was maximally inhibited at 24 hours with both 2.5 and 10 micromol/L of ADP. Marked interpatient variability in platelet aggregation in response to clopidogrel administration was observed and varied from -43 to 65%, -32 to 85% with 2.5 micromol/L at 2 hours and 24 hours and -65 to 53%, -35 to 97% with 10 micromol/L ADP at 2 hours and 24 hours. Nonresponse rate 2 hours after clopidogrel administration was 47.7%, and decreased to 29.2% at 24 hours post drug administration. CONCLUSION Clopidogrel nonresponse is prevalent among Indian patients, and there is wide interpatient variability in platelet inhibition among individual patients. However, the clinical implications of these findings need to be substantiated in larger studies with clinical end points.