Author Affiliations: Sinai Center for Thrombosis Research, Sinai Hospital of Baltimore, Baltimore, Maryland (Drs Gurbel and Tantry); and Schools of Pharmacy and Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (Dr Nolin).
Recent analyses of large-scale trials suggest either a reduced or complete lack of clinical benefit from clopidogrel therapy in nonsmokers.1- 5 Importantly, this observation is not explained by an enhanced prothrombotic state (a condition in which P2Y12 inhibitor therapy may be expected to be most effective) in smokers relative to nonsmokers as evidenced by variable event rates in smokers and nonsmokers treated with placebo. 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. Nonsmokers have greater platelet reactivity than smokers during clopidogrel treatment.6
Gurbel PA, Nolin TD, Tantry US. Clopidogrel Efficacy and Cigarette Smoking Status. JAMA. 2012;307(23):2495–2496. doi:10.1001/jama.2012.5930