口服抗血小板药治疗ACS:需牢记的十点
2015/3/27 医学论坛网

     导读

     血小板调节的血栓形成是急性冠脉综合征(ACS)的主要病理生理机制,在防治ACS方面,抗血小板治疗是重要的组成部分。

     1、 血小板调节的血栓形成是急性冠脉综合征(ACS)的主要病理生理机制,在防治ACS方面,抗血小板治疗是重要的组成部分。

     2、 追溯历史,对急性心肌梗死有益的第一个抗血小板药为阿司匹林,该药可阻断血栓素A2的形成。

     3、 CURE研究确立了阿司匹林联用P2Y12受体抑制剂氯吡格雷对非ST段抬高型ACS(NSTE-ACS)患者的益处,该研究显示,与安慰剂相比,二者联合应用可减少20%的复合终点事件,包括心血管死亡、心肌梗死和卒中。

     4、 然而,用氯吡格雷治疗ACS确实有其局限性,如发挥作用较慢,抗血小板作用不那么强。

     5、 普拉格雷是第二代噻吩并吡啶类药物,与氯吡格雷相同的是,需经细胞色素酶系从无活性形式转化为有活性的代谢产物;但与氯吡格雷不同的是,普拉格雷起效迅速且代谢为有活性成分更完全(生物利用度高)。

     6、 替格瑞洛直接作用于P2Y12受体,无需代谢激活,因此该药独立于细胞色素P450酶系。与氯吡格雷相比,替格瑞洛可快速且强效并持久地发挥作用。

     7、 鉴于在重要研究中,普拉格雷和替格瑞洛均优于氯吡格雷,因此欧洲和美国指南均支持对大多数ACS患者首选这些新型抗血小板药物联合阿司匹林作为抗血小板的一线治疗方法。值得注意的是,普拉格雷仅适用于经皮冠状动脉介入治疗(PCI)的患者。

     8、 对于大多数患者,尽管新型P2Y12抑制剂比氯吡格雷更有效,但他们也有局限性:增加出血风险,并不消除剩余缺血性风险,比氯吡格雷的价格更加昂贵,虽然比氯吡格雷起效迅速,但在一些情况下抗血小板作用可能不够充分(如ST段抬高型心肌梗死)。

     9、 当前数据显示,允许在一些第一年尚无并发症且无高出血风险的ACS患者中进行持续或长期的抗血小板治疗。

     10、 一些关于新型药物、治疗策略和药物联合治疗以及治疗持续时间的更多实验数据持续涌现,并将有助于明确未来的治疗规范。

     参考文献:

     Wiviott SD, Steg PG. Clinical Evidence for Oral Antiplatelet Therapy in Acute Coronary Syndromes. Lancet 2015;Mar 11:[Epub ahead of print].

     原文:

     The following are 10 points to remember about oral antiplatelet therapy in acute coronary syndromes (ACS):

     1. Platelet-mediated thrombosis is a major pathophysiological mechanism for ACS, and antiplatelet therapy is an important component in the treatment and prevention of ACS.

     2. Historically, the first antiplatelet agent to show benefit in acute myocardial infarction was aspirin, which blocks the production of thromboxane A2.

     3. The CURE trial established the benefits of addition of the P2Y12 receptor blocker, clopidogrel, to aspirin in patients with non-ST-segment elevation ACS, showing a 20% reduction in the composite outcome of cardiovascular death, myocardial infarction, and stroke, compared with placebo.

     4. However, clopidogrel has substantial limitations in the management of ACS with a modest inhibition of platelet aggregation and a delayed onset and offset of action.

     5. Prasugrel is a second-generation thienopyridine that, similarly to clopidogrel, needs conversion from an inactive form to an active metabolite by use of cytochromes. Unlike clopidogrel, however, prasugrel is rapidly and more wholly metabolized to its active components.

     6. Ticagrelor is a direct-acting P2Y12 antagonist that does not need metabolic activation and is therefore not dependent on cytochrome P450 enzymes. The drug acts rapidly and has more potent and consistent antiplatelet effects than clopidogrel.

     7. Since both prasugrel and ticagrelor have shown superior outcomes to clopidogrel in pivotal trials, these novel agents are now preferred to clopidogrel as a first-line therapy in conjunction with aspirin, for most patients with ACS, as endorsed by both European and US guidelines. It should be noted that prasugrel is only indicated for patients undergoing percutaneous coronary intervention.

     8. Although the novel P2Y12 blockers are more effective than clopidogrel for most patients, they also have limitations: they increase the risk of bleeding; they do not abolish the residual ischemic risk; their cost is substantially higher than clopidogrel (which is now available as a generic drug); and the rapidity of onset, although quicker than clopidogrel, could be insufficient in some settings such as ST-segment elevation myocardial infarction.

     9. Current data suggest that persistent or longer-duration antiplatelet therapy might be warranted in some patients with ACS who have not had complications in the first year and who are not at high risk of bleeding.

     10. Additional data from trials of novel agents, strategies, combinations of drugs, and for duration of therapy continue to emerge and will help define future recommendations.

     来源:医学论坛网 作者:小田 译

    

    http://www.duyihua.cn
返回 医学论坛网 返回首页 返回百拇医药