Cigarette Smoking and Antiplatelet Effects of Aspirin Monotherapy Versus Clopidogrel Monotherapy in Patients with Atherosclerotic Disease: Results of a Prospective Pharmacodynamic Study
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Smokers have a greater relative benefit of clopidogrel therapy compared with nonsmokers, likely attributed to its enhanced pharmacodynamic (PD) effects. However, to date, all PD studies have been conducted in patients on dual antiplatelet therapy with aspirin and clopidogrel, and it is unknown whether clopidogrel monotherapy can offer more effective antithrombotic effects compared with aspirin alone among smoking patients. Sixty aspirin-treated (81 mg/day) patients with vascular disease, classified as nonsmokers, light smokers, and heavy smokers according to cotinine serum levels, were enrolled. Patients were switched to clopidogrel (75 mg/day) monotherapy for 7–10 days. PD assessments were performed before and after switch by multiple electrode aggregometry (MEA) and kaolin-activated thromboelastography (TEG). Complete PD data were obtained in 57 patients (nonsmokers, n = 27; light smokers, n = 13; heavy smokers, n = 17). On treatment platelet reactivity following MEA, adenosine diphosphate (ADP) + prostaglandin E1 (PGE1) and thrombin receptor-activating peptide (TRAP) stimuli were significantly lower among heavy smokers following switch to clopidogrel. A significant inverse effect was observed with MEA arachidonic acid (ASPI), while neutral findings were shown with MEA collagen (COLL) stimulus. Thrombin and fibrin activity assessed by clot generation parameters were all nonsignificantly different but showed trends towards enhanced antithrombotic activity with clopidogrel among heavy smokers. In heavy smokers with vascular disease manifestations, clopidogrel is associated with enhanced platelet inhibitory effects, affecting purinergic and non-purinergic pathways, compared with aspirin as measured by MEA. Moreover, among smokers, clopidogrel offers trends towards enhanced effects on parameters of clot generation measured by TEG.
KeywordsSmoking Platelets Thrombus Aspirin Clopidogrel
The present study was funded by an institutional grant of the University of Florida College of Medicine-Jacksonville and by a grant provided by the James and Esther King Biomedical Research Program (1KN01-33989).
Conflict of Interest
Conflict of interest forms will be submitted offline.
Fabiana Rollini has no conflict of interest to report.
Francesco Franchi has no conflict of interest to report.
Jung Rae Cho has no conflict of interest to report.
Christopher DeGroat has no conflict of interest to report.
Mona Bhatti has no conflict of interest to report.
Elisabetta Ferrante has no conflict of interest to report.
Ronakkumar Patel has no conflict of interest to report.
Andrew Darlington has no conflict of interest to report.
Antonio Tello-Montoliu has no conflict of interest to report.
Bhaloo Desai has no conflict of interest to report.
José Luis Ferreiro received payment as an individual for (a) honoraria for lectures from Eli Lilly Co; Daiichi Sankyo, Inc.; and Astra Zeneca and (b) consulting fees from Astra Zeneca and Eli Lilly Co.
Ana Muniz-Lozano has no conflict of interest to report.
Martin M. Zenni has no conflict of interest to report.
Luis A. Guzman has no conflict of interest to report.
Theodore A. Bass has no conflict of interest to report.
Dominick J. Angiolillo received payment as an individual for (a) consulting fee or honorarium from Bristol Myers Squibb, Sanofi-Aventis, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Merck, Evolva, Abbott Vascular, and PLx Pharma; (b) Participation in review activities from Johnson & Johnson, St. Jude, and Sunovion; and (c) institutional payments for grants from Bristol Myers Squibb, Sanofi-Aventis, GlaxoSmithKline, Otsuka, Eli Lilly, Daiichi Sankyo, The Medicines Company, AstraZeneca, Evolva, and Gilead and has other financial relationships with Esther and King Biomedical Research Grant.
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