<International Circulation>:  What do you think is next for Vorapaxar?

   《国际循环》：对于Vorapaxar，下一步要做什么？
 
    Prof. Mahaffey: There is a lot to think about right now.  Within the data there are a couple of key observations that would suggest that there is potential efficacy for Vorapaxar.  What we need to sort out is how exactly to attenuate the bleeding risk with Vorapaxar.  Specifically， we saw and absolute 1.4% reduction in myocardial infarction， with a hazard ration of 0.88.  We also saw a relative 21% risk reduction， not statistically significant， for non-hemorrhagic stroke.  This indicates a signal for efficacy for Vorapaxar in atherosclerotic disease but the challenge is the bleeding events.  In TRACER， unlike the phase II trials， there was a lot of dual anti-platelet therapy.  Thienopyridine and aspirin use in nearly 90% of patients with over 90% on aspirin.  They stayed on these dual anti-platelet therapies for a long time; almost an entire year was the median duration of dual anti-platelet therapy.  Suddenly we were studying the effects of Vorapaxar on top of dual anti-platelet therapy for a very long period of time.  If we look at patients who were not on thienopyridine at baseline and who got Vorapaxar as their randomization assignment， it seemed as though there was less bleeding compared to those patients who were on thienopyridine at baseline， suggesting that with less anti-platelet therapy of aspirin and thienopyridines Vorapaxar may be safer.  I am speculating about this and we have a lot of work to do still on the blood samples we collected for these patients and we also have a wonderful opportunity with the TRA2P TIMI 50 trial that is ongoing.  This is a trial of over 25000 patients being randomized for Vorapaxar and placebo who have chronic coronary artery disease.  Those patients typically have less dual anti-platelet therapy.  I don’t know the data from that trial yet but the study may provide us with a lot of insights about the level of bleeding you may see with or without dual anti-platelet therapy， so we are very eager to see those data.  

     Mahaffey教授：目前有许多需要考虑的。数据中有几个关键的现象，提示Vorapaxar有潜在疗效。我们需要搞清的是，如何削弱Vorapaxar引起的出血风险。尤其是，我们看到心肌梗死相对风险减少1.4％，风险比0.88。我们也看到了非出血性中风相对风险减少21％，但没有统计学意义。这表明，在动脉粥样硬化性疾病中Vorapaxar有效，但面临的挑战是出血事件。在TRACER研究中，有很多双重抗血小板治疗，这与II期临床试验不同。接近90%的患者同时服用噻吩并吡啶和阿司匹林。他们进行双重抗血小板治疗很长一段时间，双重抗血小板治疗的中位数时间几乎为一整年。突然，我们开始研究在很长一段时间的双重抗血小板治疗基础上Vorapaxar的影响。如果我们研究一下那些在基线水平没有服用噻吩并吡啶并被随机分配到Vorapaxar组的患者，似乎出血要少于基线水平服用噻吩并吡啶的患者，提示少与噻吩并吡啶和阿司匹林的抗血小板治疗联用，Vorapaxar可能会更安全。我只是我的猜测，对于我们收集的这些患者的血液样本我们还有很多工作要做，我们也有一个极好的机会做进一步研究，TRA2P TIMI 50研究正在进行。这是一个纳入超过25000名慢性冠状动脉疾病患者的随机Vorapaxar和安慰剂对照研究。这些患者通常较少接受双重抗血小板治疗。我还不知道该研究的数据，但这项研究可能提供更多数据，您可能会看到伴有或不伴有双抗血小板治疗引起的出血情况，所以我们非常渴望看到这些数据。