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[Eurothrombosis2013]抗击ACS的发展历程及挑战——Lars Wallentin教授专访

作者:  L.Wallentin   日期:2013/10/29 19:10:56

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这是一个非常重要话题,也是一个棘手的问题。我认为目前稳定斑块的最佳策略可能还是降低LDL-C浓度。因为脂质浸润会启动炎性反应,使斑块软化从而增加斑块破裂风险,降低LDL-C浓度则有助于减少斑块中的脂质浸润。因此,目前来说,我认为他汀治疗是稳定斑块的最佳选择。在本届大会上,我还将讨论采用抗炎治疗降低斑块破裂风险的可能性。我将在大会的第1天,也就是周四,做这个讲座,就葛兰素史克研发的名为Darapladib、能抑制脂蛋白相关磷脂酶A2(LpPLA2)活性的新型抗炎药物进行讨论。

  <International Circulation>:  As a follow up, what do you see coming next with regards to the development of treatment with ACS?

  Prof. Lars Wallentin: That is a rather challenging question.  I will touch on that in my lecture. We have been so successful in reducing thrombotic events by the combination of antithrombotic agents and also by stenting the lesion that it is difficult to further improve outcomes, especially in the acute phase. We have tried by adding additional antithrombotic agents with new or anticoagulants for long term and even the addition of a third antiplatelet agent but, although event rates might be slightly further reduced, you get unfortunate consequences with bleeding. Therefore it seems that to further inhibition of the thrombotic process might be hazardous and associated with too much bleeding. Therefore, currently, I think the focus now should be on trying to stabilize the lesion probably eventually with more effective lipid lowering or eventually by testing anti-inflammatory agents.

  《国际循环》:您如何看待未来ACS治疗的发展方向?

  Lars Wallentin教授:这是一个非常具有挑战性的问题。在我的讲座中,我也将提到这一点。通过联用抗栓药物及在病变处放置支架我们已经成功地降低了血栓事件的发生率,因此进一步改善患者的临床结局,尤其是急性期结局具有一定的难度。我们曾试图通过长期加用抗凝剂及其他新型抗血栓药物甚至加用第三种抗血小板药物来进一步降低事件的发生率。尽管这样做之后,事件发生率能进一步小幅降低,但却会增加出血风险。因此,进一步抑制血栓形成过程可能对患者不利,会使出血风险增加。因此,我认为,目前的重点还是要通过更有效的降脂治疗或抗炎药物来积极稳定病灶。

  <International Circulation>: In your opinion, you just spoke towards how to draw a balance between the treatment of ACS and reducing the occurrence of bleeding events. What do you believe would be a very efficacious way with anticoagulation and risk of bleeding in order to have the best outcome benefit for the patients?

  Prof. Lars Wallentin: The future challenge will be to balance between the different options for antiplatelet agents like aspirin or platelet inhibition with ticagrelor and the new oral anticoagulants like rivaroxaban. I think we might need to identify which 2 of those 3 will be most effective and in which setting. Of course one hypothesis is that you might not need aspirin. But no one knows until such new strategies have been prospectively tested in new randomized trials. In addition it will be difficult to compete with aspirin because it is such a cheap and effective agent and all the new agents will be considerably more expensive while the incremental benefit in relation to the incremental cost might still be too small to replace aspirin. So I think there is an ongoing discussion within many pharmaceutical companies which direction to take. There are now several antiplatelet agents and thrombin inceptor inhibitors. Obviously we cannot use all of them in every patient so we have to identify which patients that could be tailored to the best response to a specific combination. However to come up with evidence for such a treatment approach will be a very costly undertaking. The main problem for long term treatment will be that no more than 2 antithrombic agents will be tolerated neither because of safety or based on costs.

  《国际循环》:您刚才提到了如何维持ACS治疗与降低出血事件之间的平衡。要想为患者带来最大程度的临床获益,您认为应采取怎样有效的方式来实现抗凝治疗与出血风险之间的平衡?

  Lars Wallentin教授:未来的挑战将是如何在阿司匹林、血小板抑制剂替格瑞洛及新型口服抗凝剂如利伐沙班之间进行选择。我认为,我们可能需要确定这三种药物中哪两种药物在哪种情况下最有效。当然有一种假说认为,可能我们将不再需要阿司匹林。但是,到目前为止,在得到前瞻性随机试验的验证前,没有人能肯定这一点。此外,其他药物要想与阿司匹林进行竞争还是非常困难的,因为阿司匹林既经济又有效,而其他新型制剂则相当昂贵、成本效益比较小,故而仍无法替代阿司匹林。因此,很多制药公司都在探讨未来的发展方向。目前有很多抗血小板药物及凝血酶受体抑制剂。很显然,我们不能在每位患者中都应用它们。这就需要我们来确定哪些患者对某一特定的药物联合治疗具有更好的反应性。但是,要想获得上述治疗方法的循证依据是需要投入大量资本的。长期治疗的主要问题鉴于安全性及成本考虑,可能患者无法承受两种以上的抗血栓药物。

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