双重抗血小板药物抵抗是经皮冠状动脉介入治疗后发生心血管事件的一个危险因素。

Dual antiplatelet drug resistance is a risk factor for cardiovascular events after percutaneous coronary intervention.

作者信息

Ivandic Boris T, Sausemuth Mareike, Ibrahim Hesham, Giannitsis Evangelos, Gawaz Meinrad, Katus Hugo A

机构信息

Department of Medicine III, University of Heidelberg, Germany.

出版信息

Clin Chem. 2009 Jun;55(6):1171-6. doi: 10.1373/clinchem.2008.115089. Epub 2009 Apr 9.

DOI:10.1373/clinchem.2008.115089

PMID:19359538

Abstract

BACKGROUND

Nonresponsiveness to clopidogrel and acetylsalicylic acid (ASA), a frequent result of platelet aggregometry studies, has unclear clinical and prognostic significance.

METHODS

We performed impedance aggregometry in 182 patients 12-24 h after percutaneous coronary intervention (PCI) and a 600-mg loading dose of clopidogrel, adding 5 micromol/L ADP and 1 mg/L collagen to diluted whole blood to determine platelet inhibition by clopidogrel and ASA, respectively. Samples from nonresponders were incubated in vitro with methyl-S-adenosine monophosphate or ASA to distinguish between pharmacodynamic and pharmacokinetic types of resistance. We assessed a combined primary endpoint of myocardial infarction, target vessel revascularization, late stent thrombosis, or cardiac death.

RESULTS

Nineteen patients (10.4%) were dual nonresponders (nonresponsive to both ASA and clopidogrel), and 163 patients (89.6%) were designated responders. The latter group also included 15 and 14 single nonresponders (responsive to either clopidogrel or ASA, respectively), who exhibited endpoint frequencies comparable to those of full responders (n = 134). Pharmacokinetic resistance was most prevalent. Primary endpoints occurred more frequently in dual nonresponders (n = 6, 31.6%) than in responders (n = 20, 12.3%) (relative risk 2.57; 95% CI 1.18-5.61; log-rank P = 0.03). Multivariate analysis confirmed dual nonresponsiveness (hazard ratio 2.9; 95% CI 1.17-7.2; P = 0.02) as an independent risk factor.

CONCLUSIONS

Dual nonresponders carry a high cardiovascular risk after PCI and should obtain intensified antiplatelet therapy and follow-up.

摘要

背景

血小板聚集试验中经常出现对氯吡格雷和阿司匹林（ASA）无反应的情况，其临床和预后意义尚不清楚。

方法

我们在182例经皮冠状动脉介入治疗（PCI）后12 - 24小时且服用600mg负荷剂量氯吡格雷的患者中进行了阻抗聚集试验，向稀释的全血中添加5μmol/L ADP和1mg/L胶原蛋白，分别测定氯吡格雷和ASA对血小板的抑制作用。对无反应者的样本进行体外甲基 - S - 腺苷单磷酸或ASA孵育，以区分药效学和药代动力学类型的抵抗。我们评估了心肌梗死、靶血管血运重建、晚期支架血栓形成或心源性死亡的联合主要终点。

结果

19例患者（10.4%）为双重无反应者（对ASA和氯吡格雷均无反应），163例患者（89.6%）为反应者。后一组还包括15例和14例单一无反应者（分别对氯吡格雷或ASA有反应），其终点频率与完全反应者（n = 134）相当。药代动力学抵抗最为普遍。双重无反应者（n = 6，31.6%）的主要终点发生率高于反应者（n = 20，12.3%）（相对风险2.57；95% CI 1.18 - 5.61；对数秩P = 0.03）。多变量分析证实双重无反应（风险比2.9；95% CI 1.17 - 7.2；P = 0.02）是一个独立危险因素。