The impact of smoking status on clopidogrel responsiveness in patients with coronary artery disease who undergo percutaneous coronary intervention

Background: Previous studies have pointed out the disproportionate action of clopidogrel in inhibiting platelet aggregation due to smoking more than ten cigarettes per a day. This study was designed to examine whether smoking enhances clopidogrel responsiveness in patients who are clinically diagnosed with coronary artery disease (CAD), following percutaneous coronary intervention (PCI). Methods: A total of 324 IHD participants were enrolled in a case-control study. Platelet function test was performed to all participants two hours before PCI procedure to measure clopidogrel response. Participants were then categorized into a non-responder group (case group n = 111) and responder group (control group n = 213). Each group was subdivided into a smoker group and a non-smoker group. All participants received clopidogrel loading dose equivalent to 600 mg and scheduled for elective PCI. Participants’ age, gender, family history of chronic illnesses was recorded in this study. Results: Smoking participants displayed a significant higher level of hemoglobin as compared to the non-smoking participants among the responder and the non-responder study groups (14.6±0.55 vs. 13.12±0.38, P < 0.029; 14.3±0.31 versus 12.96±0.39, P < 0.033) but lower AUC level (17±9 vs. 45±6, P < 0.005; 62±3 vs. 95±7, P < 0.008). Additionally, smoking intensity enhanced clopidogrel responsiveness by odd’s ratio 0.4213 at 95% C.I. (0.259 - 0.684), P < 0.0002. Conclusions: Current smokers had a good response to clopidogrel therapy which exerted a beneficial effect when undergoing PCI as compared to non-smokers. The marked difference in AUC between smokers and non-smokers could be related to the variance in hemoglobin level. The smokers’ paradox needs further justification to confirm this concept.