TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Am Heart J. 2011 Sep;162(3):518-26.e5. doi: 10.1016/j.ahj.2011.06.005. Epub 2011 Aug 11.
Pharmacodynamic studies reported an amplified on-clopidogrel platelet inhibition in smokers potentially caused by an increased metabolic drug activation via induction of cytochrome P450 1A2. The aims of this analysis were to evaluate the impact of smoking on the antiplatelet effect of clopidogrel and prasugrel and to test the potential interaction of smoking with the treatment effect of these drugs.
A variety of platelet function results was analyzed from 2 large cohorts of patients undergoing coronary intervention after loading with clopidogrel 600 mg (n = 2,533 and n = 1,996), a cohort of patients undergoing dose adaptation from 75 to 150 mg according to response to clopidogrel (n = 117) and a crossover trial comparing clopidogrel 150 mg with prasugrel 10 mg (n = 87). Linear regression analyses were used to test the impact of smoking on platelet function and to identify independent predictors of on-treatment platelet reactivity. The potential interaction of smoking with the clinical effect of clopidogrel versus prasugrel was analyzed in the TRITON-TIMI 38 cohort (n = 13,608).
No significant association of smoking with platelet reactivity on clopidogrel was seen in unadjusted and adjusted analyses. The variables most consistently associated with on-clopidogrel platelet function were age, sex, diabetes, and body mass index. There was no significant interaction of smoking status at presentation with the clinical efficacy of prasugrel versus clopidogrel (P for interaction = .39).
Smoking does not impact on platelet reactivity in patients after loading or on different maintenance doses of clopidogrel. The clinical treatment effect of clopidogrel versus prasugrel is not affected by smoking status at presentation.
药效动力学研究报告称，吸烟者体内氯吡格雷的血小板抑制作用增强，这可能是由于细胞色素 P450 1A2 的诱导导致药物代谢激活增加所致。本分析的目的是评估吸烟对氯吡格雷和普拉格雷抗血小板作用的影响，并检验吸烟与这些药物治疗效果的潜在相互作用。
分析了接受氯吡格雷 600mg 负荷治疗的 2 个大型患者队列（n=2533 和 n=1996）、根据氯吡格雷反应对剂量进行调整的 117 例患者队列（n=75-150mg）以及比较氯吡格雷 150mg 与普拉格雷 10mg 的交叉试验（n=87）的多种血小板功能结果。线性回归分析用于检验吸烟对血小板功能的影响，并确定治疗过程中血小板反应性的独立预测因子。在 TRITON-TIMI 38 队列（n=13608）中分析了吸烟与氯吡格雷与普拉格雷临床效果之间的潜在相互作用。
未经调整和调整分析均未发现吸烟与氯吡格雷血小板反应性之间存在显著关联。与氯吡格雷治疗过程中血小板功能最一致相关的变量是年龄、性别、糖尿病和体重指数。在研究开始时的吸烟状况与普拉格雷与氯吡格雷的临床疗效之间没有显著的交互作用（P 交互值=0.39）。
吸烟不会影响接受负荷剂量或不同维持剂量氯吡格雷治疗后的血小板反应性。吸烟状况对氯吡格雷与普拉格雷的临床治疗效果没有影响。
