Cornel Jan H, Ohman E Magnus, Neely Benjamin, Clemmensen Peter, Sritara Piyamitr, Zamoryakhin Dmitry, Armstrong Paul W, Prabhakaran Dorairaj, White Harvey D, Fox Keith A A, Gurbel Paul A, Roe Matthew T
Medisch Centrum Alkmaar, Alkmaar, the Netherlands.
Duke Clinical Research Institute, Durham, NC; Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC.
Am Heart J. 2014 Jul;168(1):76-87.e1. doi: 10.1016/j.ahj.2014.04.011. Epub 2014 Apr 24.
To further explore the impact of smoking on antiplatelet activity and treatment response, we evaluated time-dependent relationships between smoking status with on-treatment platelet reactivity and clinical outcomes for prasugrel vs. clopidogrel in patients with acute coronary syndromes managed medically without revascularization.
A total of 7062 patients aged <75 years from the primary TRILOGY ACS cohort randomized to prasugrel vs. clopidogrel were evaluated through 30 months by baseline and time-dependent smoking status with adjusted proportional-hazards models. A total of 1994 participants (28%) [corrected] were included in a platelet function sub-study evaluating serial P2Y12 reaction unit (PRU) measurements. Current smokers (n = 1566 [22%]) at baseline had fewer comorbidities compared with non-smokers; nearly half quit smoking during follow-up. Although median on-treatment PRU values were lower with prasugrel vs. clopidogrel, persistent smokers had lower serial PRU values in both treatment groups compared with non-smokers, with no differential interaction of treatment response by smoking status. The frequency of cardiovascular death, myocardial infarction, or stroke in current smokers was significantly lower with prasugrel (11.7%) vs. clopidogrel (18.6%), but there was no difference in non-smokers (13.8% vs. 13.7%), with significant interaction between treatment and baseline smoking status (P = .0002). Bleeding events occurred more frequently in prasugrel-treated patients with no significant interaction between treatment and baseline smoking status.
Among medically managed ACS patients <75 years of age, the risk of ischemic outcomes was significantly reduced with prasugrel vs. clopidogrel among smokers vs. non-smokers. No interaction between on-treatment platelet reactivity and smoking status was found.
为进一步探究吸烟对血小板活性及治疗反应的影响，我们评估了急性冠状动脉综合征且未行血运重建治疗的患者中，吸烟状态与普拉格雷和氯吡格雷治疗期间血小板反应性及临床结局之间的时间依赖关系。
对来自TRILOGY ACS原始队列的7062例年龄小于75岁、随机接受普拉格雷或氯吡格雷治疗的患者，采用校正比例风险模型，根据基线及时间依赖的吸烟状态进行了为期30个月的评估。共有1994名参与者（28%）[校正后]纳入血小板功能亚研究，评估连续的P2Y12反应单位（PRU）测量值。基线时的现吸烟者（n = 1566 [22%]）与非吸烟者相比，合并症较少；近一半在随访期间戒烟。尽管普拉格雷治疗期间的PRU中位数低于氯吡格雷，但与非吸烟者相比，两个治疗组中持续吸烟者的连续PRU值均较低，且治疗反应无吸烟状态差异交互作用。现吸烟者中，普拉格雷组心血管死亡、心肌梗死或卒中的发生率（11.7%）显著低于氯吡格雷组（18.6%），但非吸烟者中两组无差异（13.8% 对13.7%），治疗与基线吸烟状态之间存在显著交互作用（P = .0002）。出血事件在普拉格雷治疗的患者中更频繁发生，治疗与基线吸烟状态之间无显著交互作用。
在年龄小于75岁的药物治疗ACS患者中，与氯吡格雷相比，普拉格雷使吸烟者和非吸烟者的缺血性结局风险均显著降低。未发现治疗期间血小板反应性与吸烟状态之间存在交互作用。
