Desai Nihar R, Mega Jessica L, Jiang Songtao, Cannon Christopher P, Sabatine Marc S
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Am Coll Cardiol. 2009 Apr 14;53(15):1273-8. doi: 10.1016/j.jacc.2008.12.044.
The aim of this study was to examine the interaction between cigarette smoking and the clinical efficacy of clopidogrel in ST-segment elevation myocardial infarction (STEMI).
Cigarette smoking induces cytochrome P450 (CYP)1A2, which converts clopidogrel into its active metabolite, and prior studies suggest greater inhibition of platelet aggregation by clopidogrel in smokers of > or =10 cigarettes/day.
The effect of clopidogrel compared with placebo on angiographic and clinical outcomes was examined in 3,429 STEMI patients in the CLARITY-TIMI 28 (Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28) randomized trial stratified by smoking intensity as follows: not current smokers (n = 1,732), and smokers of 1 to 9 (n = 206), 10 to 19 (n = 354), 20 to 29 (n = 715), and > or =30 cigarettes/day (n = 422). Logistic regression was used to adjust for other baseline characteristics and interaction terms to test for effect modification.
Although clopidogrel reduced the rate of the primary end point of a closed infarct-related artery or death/myocardial infarction before angiography in the CLARITY-TIMI 28 trial, the benefit was especially marked among those who smoked > or =10 cigarettes/day (adjusted odds ratio [OR]: 0.49, 95% confidence interval [CI]: 0.37 to 0.66; p < 0.0001) compared with those who did not (adjusted OR: 0.72, 95% CI: 0.57 to 0.91; p = 0.006; p(interaction) = 0.04). Similarly, clopidogrel was significantly more effective at reducing the rate of cardiovascular death, myocardial infarction, or urgent revascularization through 30 days among those who smoked > or =10 cigarettes/day (adjusted OR: 0.54, 95% CI: 0.38 to 0.76; p = 0.0004) compared with those who did not (adjusted OR: 0.98; 95% CI: 0.75 to 1.28; p = 0.87; p(interaction) = 0.006).
Cigarette smoking seems to positively modify the beneficial effect of clopidogrel on angiographic and clinical outcomes. This study demonstrates that common clinical factors that influence the metabolism of clopidogrel might impact its clinical effectiveness.
本研究旨在探讨吸烟与氯吡格雷在ST段抬高型心肌梗死（STEMI）中的临床疗效之间的相互作用。
吸烟可诱导细胞色素P450（CYP）1A2，该酶可将氯吡格雷转化为其活性代谢产物，先前的研究表明，氯吡格雷对每天吸烟≥10支的吸烟者的血小板聚集抑制作用更强。
在CLARITY-TIMI 28（氯吡格雷作为辅助再灌注治疗-心肌梗死溶栓28）随机试验中，对3429例STEMI患者进行了研究，比较了氯吡格雷与安慰剂对血管造影和临床结局的影响。根据吸烟强度分层如下：非当前吸烟者（n = 1732），以及每天吸烟1至9支（n = 206）、10至19支（n = 354）、20至29支（n = 715）和≥30支（n = 422）的吸烟者。采用逻辑回归调整其他基线特征和交互项，以检验效应修正。
尽管在CLARITY-TIMI 28试验中，氯吡格雷降低了梗死相关动脉闭塞或血管造影前死亡/心肌梗死的主要终点发生率，但与不吸烟者相比，这种益处在每天吸烟≥10支的人群中尤为明显（调整后的优势比[OR]：0.49，95%置信区间[CI]：0.37至0.66；p < 0.0001）（调整后的OR：0.72，95%CI：0.57至0.91；p = 0.006；p（交互作用）= 0.04）。同样，与不吸烟者相比，氯吡格雷在降低每天吸烟≥10支的人群在30天内的心血管死亡、心肌梗死或紧急血运重建发生率方面显著更有效（调整后的OR：
