Cheng Xi, Chen Wai-Hong, Simon Daniel I
Division of Cardiology, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
Am J Cardiol. 2006 Nov 20;98(10A):11N-17N. doi: 10.1016/j.amjcard.2006.09.009. Epub 2006 Sep 28.
Numerous clinical trials have demonstrated that aspirin is effective in secondary prevention and in high-risk primary prevention of adverse cardiovascular events. However, a constellation of clinical and laboratory evidence exists that demonstrates diminished or absent response to aspirin in some patients. This has led to the concept of "aspirin resistance," which is a poorly defined, somewhat misleading term. The mechanism for aspirin resistance has not been fully established, but it is almost certainly due to a combination of clinical, biological, and genetic properties affecting platelet function. There are no criteria for distinguishing true resistance from treatment failure, and there is no consensus on whether the definition of aspirin resistance should be based on clinical outcomes, laboratory evidence, or both. Studies in large populations are needed to define antiplatelet resistance using consistent and reproducible assays and correlate the measurements with clinical outcomes. One such prospective randomized trial is completed, and 2 others are under way: the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial compared clopidogrel and aspirin with placebo and aspirin for high-risk primary or secondary prevention, and the Aspirin Nonresponsiveness and Clopidogrel Endpoint Trial (ASCET) is evaluating whether switching to clopidogrel will be superior to continued aspirin therapy in improving clinical outcomes in aspirin-resistant patients with angiographically documented coronary artery disease. The Research Evaluation to Study Individuals Who Show Thromboxane or P2Y(12) Receptor Resistance (RESISTOR) trial is investigating whether modifying antiplatelet regimens could prevent myonecrosis after percutaneous coronary intervention in patients with aspirin and clopidogrel resistance.
大量临床试验表明，阿司匹林在心血管不良事件的二级预防和高危一级预防中有效。然而，一系列临床和实验室证据表明，一些患者对阿司匹林的反应减弱或消失。这导致了“阿司匹林抵抗”这一概念的产生，这是一个定义不明确、有点误导性的术语。阿司匹林抵抗的机制尚未完全明确，但几乎可以肯定是由于影响血小板功能的临床、生物学和遗传特性共同作用所致。目前尚无区分真正抵抗与治疗失败的标准，对于阿司匹林抵抗的定义应基于临床结果、实验室证据还是两者兼而有之，也没有达成共识。需要在大量人群中进行研究，以使用一致且可重复的检测方法来定义抗血小板抵抗，并将测量结果与临床结果相关联。一项这样的前瞻性随机试验已经完成，另外两项正在进行中：氯吡格雷用于高动脉粥样硬化血栓形成风险和缺血稳定、管理及预防（CHARISMA）试验比较了氯吡格雷和阿司匹林与安慰剂和阿司匹林用于高危一级或二级预防的效果，阿司匹林无反应性和氯吡格雷终点试验（ASCET）正在评估在血管造影证实患有冠状动脉疾病的阿司匹林抵抗患者中，改用氯吡格雷是否在改善临床结果方面优于继续使用阿司匹林治疗。研究评估显示血栓素或P2Y（12）受体抵抗个体（RESISTOR）试验正在调查调整抗血小板治疗方案是否可以预防阿司匹林和氯吡格雷抵抗患者经皮冠状动脉介入治疗后的心肌坏死。
