<International Circulation>: And also is it possible the reduction of the dose to the elderly persons and those with low body weight resulted in less or similar safety profile between these two drugs because from TRITON the bleeding risk is higher with prasugrel.
Prof.  De Caterina: This was indeed demonstrated， because there was no significant excess risk of bleeding in patients over 75 or below 60 kg when they received the adjusted dose treatment compared with the clopidogrel treatment. That part of the study was successful in choosing the right dose for those patients， and now also invasively treated patients will have a regimen that is proven  to be effective and safer.  We have to say however that the primary endpoint of the study was to see whether efficacy was improved with this more intensified， antiplatelet treatment; and the hypothesis of superiority was not reached by the trial.  So by the standard criteria， the study was a negative study.
《国际循环》：而且也有可能的是对老年人和低体重人群降低药物剂量会使氯吡格雷和普拉格雷获得更低或相似的安全性，因此为TRITON试验中显示普拉格雷的出血风险更大。
　De Caterina教授：这个是此项试验中确实的结果，因为超过75岁的老年人或按照体重矫正剂量的60岁以下的人在接受矫正后治疗剂量的时候并没有发生出血风险的增加。因此我认为这部分试验在为这些患者选用合适的药物剂量的时候做的是非常成功的，而且这一结果同样可以适用于侵入性治疗的患者群，这样的治疗方案会同样有效但是更安全。我们要说的是，此项试验的首要终点是为了明确这种强化抗血小板治疗是否被证实更有效，而且这种优越性的假设并没有被试验所证实。因此对于标准而言，这项试验是一项阴性结果的研究。
<International Circulation>: We see a change after one year， there is a change of favorably effect of prasugrel versus clopidogrel.  Can you talk about that?
　De Caterina: What do we do with this trend towards late separation of the survival curves after one year?  We have to say that the trial was unique in lasting for a long time， with the meidan treatment duration of more than 14 months. This was more than any other previous trial with antiplatelet agents in this setting.  However， I have to give caution in over-interpreting this separation， because a golden rule in clinical trials is that you can do sub-group analysis when you have a positive result.  When you have a negative result， you should be extremely cautious in drawing conclusions from sub-group analysis. In that case， you commit the so-called “double sin”: first， one did not choose the right setting for demonstrating the superiority of the new treatment according to the main hypothesis; second， one tries to rescue some findings and tires to emphasize their relevance.  Certainly this is an interesting finding that requires additional thought，is worthy of speculation: and it is possible that prolonging intensified antiplatelet therapy intensified for a long period of time may lead to some survival benefits， or survival without disease benefit， but we have to remember that this is a finding relegated to a sub-group analysis.
《国际循环》：我们看到在1年以后情况发生了改变，普拉格雷的有效性要优于氯吡格雷。您能谈谈这个问题吗？
De Caterina教授：我们发现这种趋势是因为在1年以后生存曲线发生了晚期分离。我们要说的是此项试验是唯一一个持续时间超过14个月的研究，因此它比以前针对此人群进行的任何抗血小板治疗研究的时间都长。然而，我在解释这一分类的时候必须非常谨慎，因此临床试验的金标准是当得到阳性结果时你能进行亚组分析。当你获得阴性结果时就必须在对亚组分析进行结论时非常谨慎，因为你必须承认得到的结果是有两面性的。首先，没有选择正确的临床情况来选择假设的优越性，然后是试图发现一些细微的结果来放大他们的相关性。当然这是一个很有趣的发现，需要我们进行更深入的思考，可能延长强化抗血小板的治疗时间会出现生存获益或者没有疾病的生存获益，但是我们必须谨记的是这个发现只来自于低级别的亚组分析。

上一页  [1]  [2]  [3]  [4]  下一页