Heart：吸烟影响氯吡格雷药效

　　四川大学华西医院黄德嘉教授等评估了吸烟对氯吡格雷的临床和药效反应的影响。结果表明，吸烟似乎确实改变了相关临床疗效和氯吡格雷的药效，论文6月8日在线发表于《心脏》（Heart）杂志。

　　研究者检索了Medline，EMBASE和Cochrane图书馆。入选了那些记录主要心血管不良事件和通过吸烟状态进行分类的血小板对氯吡格雷反应性的临床和实验室试验。利用随机效应模型进行主要分析。对于临床研究，根据吸烟状态评估HR；对于实验室研究，评估血小板对氯吡格雷活动性的标准平均差（SMD）和血小板对氯吡格雷高反应性集合OR值。

　　结果检索了1869篇文章，包括7项临床研究和12项实验室研究共111 132例已确诊的心血管疾病患者和6658例急性冠脉综合征和/或支架置入患者，对其进行meta分析。

　　集合临床结果显示，在当前不吸烟患者中，包括氯吡格雷的强化抗血小板治疗方案与严重心血管不良事件危险降低10%相关（HR 0.90；95% CI 0.85 —0.96），在当前吸烟者中这一临床获益增加了2.9倍（HR 0.71；95% CI 0.62—0.80）。

　　实验室研究的集合分析显示，当前吸烟者血小板对氯吡格雷的反应性显著降低（SMD −0.30；95% CI −0.46 —−0.15)），但值得注意的是存在相当多的研究间异质性（P=0.000）。基于4项研究（n=1423）的分析提示，与那些从不吸烟者相比，当前吸烟者血小板对氯吡格雷的高反应性概率显著较低（OR 0.33；95% CI 0.22—0.43）。

The impact of smoking on clinical efficacy and pharmacodynamic effects of clopidogrel: a systematic review and meta-analysis.
CONTEXT
Previous findings regarding the relationship between smoking and clopidogrel effects were considerably discrepant.
OBJECTIVE
To assess the impact of smoking on clinical and pharmacodynamic response to clopidogrel.
DATA SOURCES
Medline, EMBASE and the Cochrane Library through January 2013 were searched. Reference lists of pertinent literatures and abstracts of major cardiovascular conferences were screened.
STUDY SELECTION
Clinical and laboratory studies, which reported major adverse cardiovascular events and on-clopidogrel platelet reactivity categorised by smoking status respectively, were selected.
DATA EXTRACTION
Descriptive and quantitative data were extracted. The main analyses were performed under a random-effects model. For clinical studies, HR estimates were synthesised according to smoking status; for laboratory studies, standardised mean difference (SMD) of on-clopidogrel platelet reactivity and OR for high on-clopidogrel platelet reactivity were pooled. Heterogeneity was quantified by computing I2 statistic.
RESULTS
Of the 1869 citations retrieved, seven clinical studies and 12 laboratory studies involving 111 132 patients with established cardiovascular disease and 6658 patients with acute coronary syndrome and/or stent deployment, respectively, were included for meta-analysis. Pooled clinical results showed that an intensified antiplatelet regimen involving clopidogrel was associated with 10% reduced risk for major adverse cardiovascular events among non-current smokers (HR 0.90; 95% CI 0.85 to 0.96), while this clinical benefit was enhanced by 2.9-fold among current smokers (HR 0.71; 95% CI 0.62 to 0.80). Pooled analysis of laboratory studies revealed that current smokers had significantly lower on-clopidogrel platelet reactivity (SMD -0.30; 95% CI -0.46 to -0.15) but, notably, there was considerable inter-study heterogeneity (I2 76.2%; p=0.000). The analysis based on four studies (n=1423) suggested a significantly lower odds of high on-clopidogrel platelet reactivity among current smokers than those among never smokers (OR 0.33; 95% CI 0.22 to 0.43).
CONCLUSIONS
Smoking appears to positively modify the relative clinical efficacy and pharmacodynamic effects of clopidogrel.