Riva Letizia, Di Pasquale Giuseppe, Casella Gianni, Calabrese Daniela, Zagnoni Silvia, Pallotti Maria Giovanna
Unità Operativa di Cardiologia, Ospedale Maggiore, Azienda USL di Bologna, Bologna.
G Ital Cardiol (Rome). 2010 Dec;11(12 Suppl 3):27S-33S.
Antiplatelet therapy plays a pivotal role in the treatment of patients with acute coronary syndromes (ACS), inducing a significant reduction of ischemic events. Aspirin treatment is associated with a substantial 50% reduction of death or myocardial infarction in patients with ACS, but it is usually combined with other antiplatelet agents in order to achieve a more profound inhibition of platelet aggregation. Ticlopidine was initially used in association with aspirin in patients treated with percutaneous coronary interventions (PCI), demonstrating a dramatic reduction of the risk of stent thrombosis. Later on it has been replaced by clopidogrel, which now represents in combination with aspirin the standard treatment of patients with ACS treated either medically or invasively, with a 20% risk reduction in comparison with aspirin alone. The limitation of clopidogrel resistance, documented in about 30% of patients because of genetic factors, clinical factors, and pharmacokinetic factors (i.e., poor absorption and drug-drug interactions), has promoted the development of third generation thienopiridines. Prasugrel, which is a more potent and faster inhibitor of platelet aggregation, in comparison with clopidogrel is associated with a further 20% reduction of ischemic events with an increase of major bleedings in patients with ACS undergoing PCI. It is therefore recommended for patients with ACS at high ischemic risk and at non-high hemorrhagic risk. Ticagrelor, a reversible antagonist of P2Y12 platelet receptor, in comparison with clopidogrel is associated with a 16% reduction of ischemic events, including a significant reduction of death from vascular causes, without increasing the rate of overall major bleeding. Intravenous cangrelor, which has been compared with clopidogrel in patients with ACS undergoing PCI, yielded negative results. The use of glycoproteins IIb/IIIa inhibitors (abciximab, eptifibatide, tirofiban) is no longer recommended as upstream therapy in patients with ACS undergoing PCI, but only in the periprocedural phase. New selective antagonists of thrombin receptor 1 (PAR-1), on top of the standard dual antiplatelet therapy, are now under investigation in patients with ACS and in the secondary prevention. In conclusion, an accurate evaluation is warranted of the balance between ischemic and hemorrhagic risk when deciding the choice of antiplatelet treatment in the individual patient. The hope for the future is the development of new selective platelet inhibitors with higher antischemic efficacy and better hemorrhagic profile.
抗血小板治疗在急性冠脉综合征（ACS）患者的治疗中起着关键作用，可显著减少缺血事件。阿司匹林治疗可使ACS患者的死亡或心肌梗死风险大幅降低50%，但通常需与其他抗血小板药物联合使用，以更有效地抑制血小板聚集。噻氯匹定最初与阿司匹林联合用于接受经皮冠状动脉介入治疗（PCI）的患者，可显著降低支架血栓形成风险。后来它被氯吡格雷取代，氯吡格雷与阿司匹林联合用药目前是ACS患者药物治疗或介入治疗的标准方案，与单用阿司匹林相比，风险降低20%。约30%的患者因遗传因素、临床因素和药代动力学因素（即吸收不良和药物相互作用）存在氯吡格雷抵抗现象，这促使了第三代噻吩并吡啶类药物的研发。普拉格雷是一种更强效、起效更快的血小板聚集抑制剂，与氯吡格雷相比，可使接受PCI的ACS患者的缺血事件进一步减少20%，但大出血风险增加。因此，推荐用于缺血风险高且出血风险不高的ACS患者。替格瑞洛是P2Y12血小板受体的可逆拮抗剂，与氯吡格雷相比，可使缺血事件减少16%，包括血管性死亡显著减少，且不增加总体大出血发生率。在接受PCI的ACS患者中，静脉注射坎格雷洛与氯吡格雷相比，结果为阴性。糖蛋白IIb/IIIa抑制剂（阿昔单抗、依替巴肽、替罗非班）不再推荐作为接受PCI的ACS患者的上游治疗药物，仅在围手术期使用。新型凝血酶受体1（PAR-1）选择性拮抗剂，在标准双联抗血小板治疗基础上，目前正在ACS患者及二级预防中进行研究。总之，在为个体患者选择抗血小板治疗时，有必要准确评估缺血和出血风险之间的平衡。未来的希望是研发出具有更高抗缺血疗效和更好出血特征的新型选择性血小板抑制剂。
