Perspective:

Recent analyses of large-scale trials suggest either a reduced or complete lack of clinical benefit from clopidogrel therapy in nonsmokers. Cigarette smoking induces the activity of cytochrome P450 (CYP) 1A2, an isoenzyme involved in the metabolic activation of clopidogrel, but less recognized in importance than CYP2C19. In fact, nonsmokers have greater platelet reactivity than smokers during clopidogrel treatment. These observations raise concerns about the costs and potential risks incurred by treating nonsmokers with clopidogrel. The clopidogrel-smoking interaction deserves further research, and may be related to the influence of cigarette smoking on CYP activity. The influence of smoking status on clopidogrel metabolism is currently being evaluated in a prospective study, ‘The Influence of Smoking Status on Prasugrel and Clopidogrel Treated Subjects Taking Aspirin and Having Stable Coronary Artery Disease,’ which should provide additional insight. The primary hypothesis of the study is that smoking status will influence the antiplatelet effects and active metabolite concentrations of clopidogrel, but will have no impact on prasugrel’s antiplatelet effects or active metabolite concentrations.