Division of Clinical Epidemiology, Geneva University Hospital, Geneva, Switzerland.
J Thromb Haemost. 2010 May;8(5):923-33. doi: 10.1111/j.1538-7836.2010.03809.x. Epub 2010 Feb 12.
BSUMMARY BACKGROUND: Previous studies have shown an important risk of cardiovascular events in patients with clopidogrel biological non-response, and data have shown considerable, unexplored heterogeneity.
To evaluate the magnitude of cardiovascular risk associated with clopidogrel non-response and to explore heterogeneity.
This was a systematic review and meta-analysis of prospective studies of patients treated with clopidogrel for symptomatic atherothrombosis, evaluated by light transmission aggregometry with ADP and monitored prospectively for clinical ischemic events.
Fifteen studies were included, totaling 3960 patients, of whom 25% were considered to be clopidogrel non-responders. The global relative risk (RR) for recurrent ischemic events in clopidogrel non-responders was 3.5 [95% confidence interval (CI) 2.4-5.2, P < 0.0001]. The results of the different studies were heterogeneous (Cochran P = 0.01 and I(2) = 52%). The most recent studies yielded lower RRs [global RR = 2.9 (95% CI 2.3-3.8) after 2007, and global RR = 6.6 (95% CI 3.7-11.9) before 2007, P = 0.01]. Heterogeneity was present in the group of studies in which more than 10% of patients took glycoprotein (GP)IIb-IIIa inhibitors [Cochran P = 0.003 and I(2) = 70%; RR = 3.8 (95% CI 2.9-5.1)] and was absent in the other studies [Cochran P = 0.88 and I(2) = 0; RR = 2.5 (95% CI 1.7-3.6)]. The RR was significantly higher in studies using higher ADP maximal aggregation cut-offs (> 65%) for clopidogrel non-response than in studies using lower cut-offs [RR = 5.8 (95% CI 3.2-10.3) and RR = 2.9 (95% CI 2.2-3.7), respectively, P = 0.03].
The risk of ischemic events associated with clopidogrel non-response is now more precisely defined. The risk is heterogeneous across studies, possibly because of an interaction with GPIIb-IIIa inhibitors and the use of different cut-offs to identify non-responders.
先前的研究表明，氯吡格雷生物无反应患者发生心血管事件的风险很高，且数据显示存在大量未被探索的异质性。
评估氯吡格雷无反应与心血管风险的关联程度，并探索其中的异质性。
这是一项系统性综述和前瞻性研究的荟萃分析，纳入了接受氯吡格雷治疗有症状动脉粥样硬化血栓形成的患者，采用 ADP 诱导的光传输聚集法进行评估，并前瞻性监测临床缺血事件。
共纳入 15 项研究，总计 3960 例患者，其中 25%被认为是氯吡格雷无反应者。氯吡格雷无反应者发生复发性缺血事件的全球相对风险（RR）为 3.5[95%置信区间（CI）2.4-5.2，P＜0.0001]。不同研究的结果存在异质性（Cochran P=0.01，I²=52%）。最近的研究得出的 RR 值较低[2007 年后的全球 RR=2.9（95%CI 2.3-3.8），2007 年前的全球 RR=6.6（95%CI 3.7-11.9），P=0.01]。在超过 10%的患者使用糖蛋白（GP）IIb-IIIa 抑制剂的研究组中存在异质性（Cochran P=0.003，I²=70%；RR=3.8（95%CI 2.9-5.1）），而在其他研究中则不存在异质性（Cochran P=0.88，I²=0；RR=2.5（95%CI 1.7-3.6））。对于氯吡格雷无反应，使用较高 ADP 最大聚集截止值（＞65%）的研究RR 值显著高于使用较低截止值的研究[RR=5.8（95%CI 3.2-10.3）和 RR=2.9（95%CI 2.2-3.7），P=0.03]。
目前，氯吡格雷无反应相关缺血事件风险的定义更加准确。风险在不同研究中存在异质性，这可能是由于与 GPIIb-IIIa 抑制剂的相互作用以及使用不同的截止值来识别无反应者所致。
