These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Cigarette smoking is associated with a dose-response effect in clopidogrel-treated patients with diabetes mellitus and coronary artery disease: results of a pharmacodynamic study.
    Author: Ueno M, Ferreiro JL, Desai B, Tomasello SD, Tello-Montoliu A, Capodanno D, Capranzano P, Kodali M, Dharmashankar K, Charlton RK, Bass TA, Angiolillo DJ.
    Journal: JACC Cardiovasc Interv; 2012 Mar; 5(3):293-300. PubMed ID: 22440495.
    Abstract:
    OBJECTIVES: This study sought to assess the presence of a dose-response effect of cigarette smoking and its impact on high on-treatment platelet reactivity (HPR) in patients with diabetes mellitus treated with clopidogrel. BACKGROUND: Cigarette smoking is an inducer of cytochrome P450 1A2, a hepatic enzyme involved in clopidogrel metabolism. If cigarette smoking is associated with a dose-response effect on pharmacodynamic measures in clopidogrel-treated patients is unknown. METHODS: A total of 134 type 2 diabetes mellitus patients on maintenance aspirin and clopidogrel therapy were studied. Patients were divided into 3 groups according to cotinine levels: <3 ng/ml (nonsmokers), 3 to 199 ng/ml (light smokers), and ≥ 200 ng/ml (heavy smokers). Platelet function was assessed by light transmittance aggregometry, VerifyNow P2Y12 assay (Accumetrics, San Diego, California), and vasodilator-stimulated phosphoprotein. Rates of HPR were defined using established cutoff values. RESULTS: A dose-response effect was observed for all pharmacodynamic parameters tested. Serum cotinine levels were inversely associated with platelet reactivity as assessed by light transmittance aggregometry using 5 and 20 μmol/l adenosine diphosphate (p < 0.0001 for all). Accordingly, platelet disaggregation increased with levels of serum cotinine (p < 0.0001). Similar results were found with P2Y(12) reaction units (p < 0.0001) and inhibition of platelet aggregation (p = 0.005) as defined by VerifyNow P2Y12 testing, and platelet reactivity index (p = 0.002) as assessed by vasodilator-stimulated phosphoprotein. Higher serum cotinine levels were significantly associated with lower rates of HPR, as defined according to various pharmacodynamic cutoff measures. CONCLUSIONS: Cigarette smoking is associated with a dose-response effect on clopidogrel-induced antiplatelet effects and lower rates of HPR in diabetes mellitus patients.
    [Abstract] [Full Text] [Related] [New Search]