Galli M, Maggioni A P, Vassanelli C, Tavazzi L
Divisione di Cardiologia, Fondazione Salvatore Maugeri, IRCCS, Veruno.
Ital Heart J Suppl. 2000 Feb;1(2):202-11.
Acute coronary syndromes not associated with ST-segment elevation, i.e. unstable angina and non-Q wave myocardial infarction, represent a heterogeneous group of clinical disorders sharing similar pathogenic mechanisms, clinical presentation and medical management. Current guidelines recommended an early anti-thrombotic and anti-ischemic treatment in these patients, as well as their prompt risk evaluation based on easily available clinical and instrumental data, to identify those subjects at greater risk in whom a more aggressive management is warranted. Despite the association of aspirin, heparin and anti-ischemic drugs, the 30-day rate of death or myocardial infarction remains high (9-15%) in patients with markers of greater risk (i.e. Braunwald class III, ST-segment depression, abnormal creatine kinase or troponin values). Moreover, in patients with acute coronary syndromes undergoing percutaneous coronary interventions (PCI), complex coronary lesions increase the peri-procedural risk of thrombotic complications. Regardless of the agonist responsible for platelet activation and aggregation, platelet glycoprotein (GP) IIb/IIIa receptor activation is the key factor in thrombosis formation. Several clinical trials in the past few years have documented the beneficial value of GP IIb/IIIa inhibitors in patients treated with aspirin and heparin, with a significant reduction in the cumulative end-point of death and/or myocardial infarction at 48-96 hours (odds ratio--OR 0.81, 95% confidence interval--CI 0.71-0.92, p < 0.01). Such therapeutical benefit is still present at 30 days (OR 0.88, 95% CI 0.81-0.97, p < 0.001) and 6 months (OR 0.88, 95% CI 0.79-0.97, p < 0.001). In patients treated with abciximab, eptifibatide or tirofiban, undergoing early PCI, a remarkable relative reduction in the risk of death and non-fatal acute myocardial infarction was shown before PCI (-34%, p < 0.001). The pre-PCI administration of GP IIb/IIIa inhibitors is associated with a significant reduction in peri-procedural complications (-41% relative reduction of death or acute myocardial infarction in the 48 hours after PCI, p < 0.001). In this subset of patients the benefit correlates with abnormal pre-PCI values of troponin, a reliable surrogate marker of active thrombosis. The greatest clinical benefit from GP IIb/IIIa inhibitors is expected in patients presenting high-risk features (early post-infarction angina; older age with a history of left ventricular dysfunction or diabetes; heart failure symptoms, ST-segment depression, abnormal troponin, creatine kinase, and C-reactive protein values at admission) as well as in patients with recurrent ischemic attacks and those undergoing early PCI. Although the combination of GP IIb/IIIa inhibition and standard doses of unfractionated heparin is associated with an increased risk of major bleeding, such risk can be remarkably reduced adopting simple technical suggestions.
非ST段抬高型急性冠状动脉综合征,即不稳定型心绞痛和非Q波心肌梗死,是一组临床病症,具有相似的发病机制、临床表现和治疗方法。当前指南建议对这些患者尽早进行抗血栓和抗缺血治疗,并根据易于获取的临床和检查数据对其进行快速风险评估,以识别那些需要更积极治疗的高风险患者。尽管使用了阿司匹林、肝素和抗缺血药物,但高风险患者(即Braunwald III级、ST段压低、肌酸激酶或肌钙蛋白值异常)的30天死亡或心肌梗死发生率仍然很高(9%-15%)。此外,在接受经皮冠状动脉介入治疗(PCI)的急性冠状动脉综合征患者中,复杂冠状动脉病变会增加围手术期血栓形成并发症的风险。无论引起血小板激活和聚集的激动剂是什么,血小板糖蛋白(GP)IIb/IIIa受体激活都是血栓形成的关键因素。过去几年的多项临床试验证明了GP IIb/IIIa抑制剂在接受阿司匹林和肝素治疗的患者中的有益作用,48-96小时内死亡和/或心肌梗死的累积终点显著降低(优势比——OR 0.81,95%置信区间——CI 0.71-0.92,p<0.01)。这种治疗益处在30天时仍然存在(OR 0.88,95%CI 0.81-0.97,p<0.001),在6个月时也是如此(OR 0.88,95%CI 0.79-0.97,p<0.001)。在接受阿昔单抗、依替巴肽或替罗非班治疗并进行早期PCI的患者中,PCI前死亡和非致命性急性心肌梗死风险显著相对降低(-34%,p<0.001)。PCI前给予GP IIb/IIIa抑制剂与围手术期并发症显著减少相关(PCI后48小时内死亡或急性心肌梗死相对减少41%,p<0.001)。在这部分患者中,益处与PCI前肌钙蛋白异常值相关,肌钙蛋白是活动性血栓形成的可靠替代标志物。预计GP IIb/IIIa抑制剂在具有高风险特征的患者(梗死后早期心绞痛;有左心室功能障碍或糖尿病病史的老年患者;心力衰竭症状、入院时ST段压低、肌钙蛋白、肌酸激酶和C反应蛋白值异常)以及复发性缺血发作患者和接受早期PCI的患者中临床获益最大。尽管GP IIb/IIIa抑制与标准剂量普通肝素联合使用会增加大出血风险,但采用简单的技术建议可显著降低这种风险。