Cigarette Smoking Enhances Clopidogrel’s Antiplatelet Benefits

Researchers have identified a dose-response effect of cigarette smoking on high platelet reactivity (HPR) in patients with diabetes mellitus who were treated with clopidogrel, according to a study appearing in JACC Interventions.

Serum levels of cotinine were used to measure the amount of nicotine exposure in 134 patients with type 2 diabetes on maintenance aspirin and clopidodgrel therapy; patients were divided into three groups according to cotinine levels (< 3 ng/ml, 3-199 ng/ml, ≥ 200 ng/ml).

After adjusting for age, insulin treatment, use of statin, body mass index, and other variables, the researchers reported that a dose-response effect was observed for all pharmacodynamic parameters tested. Serum cotinine levels were inversely associated with levels of on-treatment HPR, with light and heavy smokers being less likely to have HPR than non-smokers. Also, as serum cotinine levels increased, so did platelet disaggregation.

“In addition to demonstrating the impact of cotinine levels on the degree of platelet reactivity, our study showed a dose-response profile on the prevalence of rates of HPR,” the study authors concluded. “Importantly, our findings were consistent using multiple pharmacodynamic parameters and confirmed in multivariate analysis.”

“Although clopidogrel effects are enhanced in smokers compared with non-smokers,” Dominick Angiolillo, MD, PhD, the study’s corresponding author, told CardioSource WorldNews, “CV event rates, including mortality, still remain markedly higher among smokers.” Dr. Angiolillo added, “While the optimal health care saving goal to reduce atherothrombotic risk is smoking cessation, this objective is not always achieved and many patients continue to smoke. Therefore, defining the optimal anti-platelet treatment strategy in these patients becomes of key importance.”


  1. Ueno M, Ferreiro JL, Desai B, et al. J Am Coll Cardiol Intv. 2012;5(3):293-300.

Keywords: Cotinine, Nicotine, Multivariate Analysis, Diabetes Mellitus, Type 2, Smoking Cessation, Smoking, Goals

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