[ACC2013]ACS个体化治疗及最新临床试验——英国爱丁堡大学Keith A. A. Fox教授采访
Keith A. A. Fox教授 英国爱丁堡大学
<International Circulation>: What were your opinions of the TRILOGY ACS trial?
《国际循环》:您对TRILOGY ACS试验有什么看法?
Prof. Fox: The TRIOLOGY trail was previously presented and published. What was being presented at this ACC13 were the two further analyses which were based on the Proton Pump Inhibitor drugs and also smoking status. The interesting finding is that there did seem to be an interaction with PPI usage and the results of the trial. Any analysis is a subsidiary analysis and has to be seen as exploratory rather than definitive.
Fox教授:TRILOGY试验的结果已经公布并且发表。ACC 13的报告是关于这个研究的两个进一步分析。这两个分析基于质子泵抑制剂(PPI)和吸烟状态。有意思的发现是PPI使用和试验结果之间似乎的确存在相互作用。任何事后分析都是探索性的而非确切的。
<International Circulation>: Did this have any clinical implications?
《国际循环》:这个分析有临床意义吗?
Prof. Fox: These results were interesting, but we could not call them definitive.
Fox教授:这些结果很有意思,但是我们并不能把他们称为确切依据。
<International Circulation>: What are some controversies when it comes to the personalization of therapy for ACS?
《国际循环》:关于ACS的个体化治疗方面有哪些争议?
Prof. Fox: The main controversies are how to personalize therapy. The majority of clinicians are not personalizing therapy with regard to risk status. Many of us would advocate the need to risk stratify patients. In AF, we accept the importance of the CHADS2 score, the CHADS-Vas score and by doing that and analyzing bleeding risk, we have a much better idea of those that are likely to benefit versus those for whom it might be hazardous. In ACS, the score with the most international validation is the GRACE RISK score and that has shown a very powerful risk prediction, all the way out to five years. It has served to identify those who benefit from more intensive, long-term treatment. This is quite a valuable addition. At much more specific level, the question is whether to personalize therapy based on other biomarkers. Obviously we do that with makers like troponin, like in HF with BNP or NT-proBNP, but we don’t yet stratify based on platelet function assays. The studies the studies that have been done to-date, like GAVITAS and ARTIC don’t provide evidence to support that. The long term impact of the TIROLOGY study, the impact on platelet function measure as platelet reactivity unit with fine measurements. Although prasidgrel was more effective in changing platelet function, there wasn’t a significant impact on outcome. There has been a disconnect between platelet reactivity units and the hard measures of outcome. That contrast with other areas where there is connection, like toponin or BPN. The next stage is the genetic assays, where there is evidence that there is an association between for example, the way in which different populations metabolized warfarin. While those assays are available, they are not widely used. Although there is the potential and we will have more information form the large trials. For example looking at P2Y-12 metabolism and platelet function and outcome, as yet, I don’t think it is at the edge of applying this in practice.
Fox教授:主要争议在于如何个体化治疗。大部分临床医生不会根据患者危险状态进行个体化治疗。我们提倡需对患者危险分层。在房颤中,我们认同CHADS2和CHADS2-VASC评分的重要性,通过进行评分,分析出血风险,我们对高危患者的治疗有更好想法。对ACS,国际上认可度最高的评分是GRACE危险评分,这个评分5年内危险预测能力一直很强。评分可以识别哪些患者能够从长期强化治疗中获益。这个评分非常有价值。在更特异的水平上,是否应当进行个体化治疗基于其他的生物标志物。很显然,我们根据(例如肌钙蛋白)一些标志物进行个体化治疗,就像心衰中使用BNP和NT-proBNP一样。但我们还没能够根据血小板功能检查进行危险分层。目前已经完成的研究如GAVITAS和ARTIC并没有提供支持血小板功能检查的证据。TRILOGY研究的长期影响是血小板功能检查。尽管普拉格雷在改善血小板功能方面效果更好,但并没有显示对结局有显著影响。血小板功能和结局硬终点之间存在断层。与其他生物标志物,如肌钙蛋白或BNP和硬终点的联系形成对比。下一步是基因学检查。有证据证实不同人群华法林代谢存在差异。尽管这些检查可以进行,但并没有广泛使用。这些检查有潜在价值,我们会从大型试验中得到更多信息。例如我们在观察P2Y-12代谢与血小板功能和结局之间的关系。我认为这些检查方法还没到即将可以应用地步。
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