Wiviott Stephen D
TIMI Study Group, Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA.
Am J Cardiol. 2006 Nov 20;98(10A):18N-24N. doi: 10.1016/j.amjcard.2006.09.010. Epub 2006 Sep 28.
Dual antiplatelet therapy represents an important advance for patients with established cardiovascular disease. Variable platelet response and potential resistance to therapy have emerged with aspirin and clopidogrel. There is no clear and accepted definition of clopidogrel resistance, but patients with lower responses to clopidogrel are at risk for ischemic events, particularly when they undergo percutaneous coronary intervention. Inconsistent nomenclature about this lower response has led to confusion about its potential clinical importance. The concern about nomenclature is less important than answers to key questions such as its mechanisms, how and in whom to measure platelet function, what levels of inhibition are associated with failure of therapy, what levels are adequate for improved clinical outcomes, and in what ways therapy could be altered in patients with lower responses to improve measures of platelet function and clinical outcomes. One option may be to target more aggressive intervention (higher loading and maintenance doses of clopidogrel or alternative agents) to specific patients who are at greater risk and/or least responsive to standard therapies. Clinically useful risk stratification requires an easily performed and reproducible measure of platelet aggregation, as well as standardized definitions of response that correlate with clinical outcomes. Point-of-care assays of platelet function may ultimately improve the ability of clinicians to modify therapy on the basis of response.
双联抗血小板治疗是已确诊心血管疾病患者治疗方面的一项重要进展。使用阿司匹林和氯吡格雷时出现了血小板反应变异性及对治疗的潜在抵抗。氯吡格雷抵抗尚无明确且被广泛接受的定义，但对氯吡格雷反应较低的患者发生缺血事件的风险较高，尤其是在接受经皮冠状动脉介入治疗时。关于这种较低反应的命名不一致，导致人们对其潜在临床重要性感到困惑。对命名的担忧不如回答关键问题重要，这些问题包括其机制、如何以及对谁进行血小板功能检测、何种抑制水平与治疗失败相关、何种水平对改善临床结局足够，以及对反应较低的患者如何改变治疗以改善血小板功能检测指标和临床结局。一种选择可能是针对风险更高和/或对标准治疗反应最差的特定患者进行更积极的干预（更高负荷剂量和维持剂量的氯吡格雷或替代药物）。临床上有用的风险分层需要一种易于操作且可重复的血小板聚集检测方法，以及与临床结局相关的标准化反应定义。血小板功能的即时检测最终可能会提高临床医生根据反应调整治疗的能力。
