title: Cigarette smoking and antiplatelet effects of aspirin monotherapy versus clopidogrel monotherapy in patients with atherosclerotic disease: results of a prospective pharmacodynamic study.
abstract: 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.
authors.affiliation: University of Florida College of Medicine-Jacksonville, 655 West 8th Street, Jacksonville, FL, 32209, USA.
authors.forename: Fabiana
authors.initials: F
authors.lastname: Rollini
authors.forename: Francesco
authors.initials: F
authors.lastname: Franchi
authors.forename: Jung Rae
authors.initials: JR
authors.lastname: Cho
authors.forename: Christopher
authors.initials: C
authors.lastname: Degroat
authors.forename: Mona
authors.initials: M
authors.lastname: Bhatti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ferrante
authors.forename: Ronakkumar
authors.initials: R
authors.lastname: Patel
authors.forename: Andrew
authors.initials: A
authors.lastname: Darlington
authors.forename: Antonio
authors.initials: A
authors.lastname: Tello-Montoliu
authors.forename: Bhaloo
authors.initials: B
authors.lastname: Desai
authors.forename: Joséluis
authors.initials: J
authors.lastname: Ferreiro
authors.forename: Ana
authors.initials: A
authors.lastname: Muniz-Lozano
authors.forename: Martin M
authors.initials: MM
authors.lastname: Zenni
authors.forename: Luis A
authors.initials: LA
authors.lastname: Guzman
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Bass
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D000077144:Clopidogrel; D003367:Cotinine / Q000097:blood; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D011446:Prospective Studies; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects / Q000097:blood*; D013916:Thrombelastography; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis / Q000517:prevention & control*; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D003367:Cotinine; D013988:Ticlopidine; D001241:Aspirin