International Circulation: Recently， your research on patients with everolimus-eluting stents suggested there was no difference in myocardial infarction and stent thrombosis in DAPT for six months or more than twelve months. Does that suggest that the DAPT duration should be individualized according to different types of DES?
　　Dr Kandzari: That’s right. Increasingly our attention has been directed towards abbreviated dual antiplatelet therapy regimens. As a background， the concerns over the long-term adherence to dual antiplatelet therapy and societal guidelines that recommend one year for instance as a minimum of dual antiplatelet therapy and then physician perceptions for some who say it is a lifetime if you receive a drug-eluting stent. These are all of the dilemmas and barriers to the more widespread utilization of DES extending the benefits of drug-eluting stents to our patients. Yet increasingly we realize that there is nothing magical about twelve months of dual antiplatelet therapy. In fact longer durations as represented recently in the PRODIGY trial may be associated with a safety hazard of increased bleeding risk. Yet other studies， like PRODIGY， and many observational studies seem to suggest that at least beyond six months continuing long-term dual antiplatelet therapy may not necessarily reduce the risks of stent thrombosis. In some of the comparative trials specifically with Endeavour， we observed that with paclitaxel-eluting stents， for example， more than half of the patients who had very late stent thromboses were on dual antiplatelet therapy at the time of the event. Again it reminds us that not only do outcomes of stent thrombosis likely differ according to different types of drug-eluting stents， but whether dual antiplatelet therapy is altogether protective against very late stent thrombosis may also vary according to the stent type. That led us to perform this evaluation among the entire Endeavour clinical trial program that represented roughly 2100 patients treated with the Endeavour stent. When we retrospectively evaluated whether patients were taking dual antiplatelet therapy for only six months versus one year versus two years and evaluating these outcomes of death， myocardial infarction and of stent thrombosis through three years of follow-up， we found that there were no differences whatsoever across the different groups relative to the duration of dual antiplatelet therapy. By no means are these data conclusive either. This was an observational analysis， but it is very much in accord with the entire program with Endeavour that suggests a very favorable safety profile and a very low risk of stent thrombosis. We are seeing this now also with other emerging DES programs， with everolimus- and alternative zotarolimus-eluting stenting programs. What is really needed though is to finally put this hypothesis to a formal adequate test and conduct prospective studies of adequate power to determine whether there are potential differences in duration or advantages in even further abbreviating durations of dual antiplatelet therapies. Once we have this data which challenges our existing paradigms of one year or lifetime， I think this will again broaden the opportunity for drug-eluting stent treatment for many more patients.
　　《国际循环》：近期，您对置入依维莫司系统支架的患者的研究结果提示，接受双联抗血小板治疗（DAPT）6个月或超过12个月的患者，心肌梗死和支架内血栓形成的发生率无显著差异，这是否提示应根据DES的类型来决定患者接受DAPT的疗程？
　　Dr Kandzari：是的。我们的注意力越来越多地转向缩短双联抗血小板药物的用药时间。这种变化的背景是，学会指南建议患者服用双联抗血小板药物至少1年，一些医生甚至认为置入药物洗脱支架的患者应终生接受DAPT，人们对此逐渐产生了担忧。这些观念和建议已成为广泛推广药物洗脱支架以使更多患者获益的困境和障碍。我们越来越认识到，进行长达12个月的双联抗血小板治疗并无任何神奇的益处。实际上，正如近期公布的PRODIGY试验所表明的，延长DAPT疗程可能与出血风险的增加密切相关。PRODIGY和许多观察性研究还提示我们，至少超过6个月的双联抗血小板治疗可能不能降低支架内血栓形成的风险。在一些对比研究尤其是Endeavour的试验中，我们观察到置入紫杉醇洗脱支架后发生极晚期支架内血栓形成的患者，超过半数发生事件时正在服用双联抗血小板药物。这再次提醒我们，不仅支架内血栓形成的结果可能因DES类型不同而不同，而且双联抗血小板疗法能否共同预防极晚期支架内血栓形成也与DES的不同类型有关。这促使我们对Endeavour临床试验中接受Endeavour支架置入的2100例患者进行了这项评估。将接受DAPT仅6个月、1年、2年的患者进行回顾性分析，比较其3年随访期间死亡、心肌梗死和支架内血栓形成的发生率，我们发现3组间上述事件发生率并无差异。当然这些数据不能得出明确结论，这是一项观察性分析，但这些结果与Endeavour试验的总体结果高度一致，后者提示Endeavour支架安全性有优势，支架内血栓形成的发生率非常低。而现在，我们在依维莫司、佐他莫司等其他DES临床试验中看到了同样的结果。当前真正需要的是最终将这一假设进行正式的检验，实施前瞻性、有足够统计效能的研究，以确定DAPT疗程是否导致差异，甚至更短的疗程有无益处。一旦有了这些数据，将对现行的1年或终生服药的治疗模式提出挑战，我认为这将进一步拓展DES应用于更多患者的机遇。
　　International Circulation: What is it going to take to get that data?
　　Dr Kandzari: At present there are numerous trials comparing different durations of dual antiplatelet therapy. Unfortunately， while most of these studies are randomized trials which is a step in the right direction， most of them are statistically underpowered. In fact， the only large trial which exceeds well more than 20000 patients is a trial that is comparing twelve months versus thirty months but I think what the clinical community is asking for now is evaluating six months or maybe even shorter durations. In many ways too， the clinical question is not can we stop dual antiplatelet therapy for all patients at say six months， but is it safe for selected patients to do so. As in all medicine， there is variability across all individual patients so identifying those patients for whom we can abbreviate dual antiplatelet therapy which may be very specific to a selected type of drug-eluting stent rather than a class of drug-eluting stent， these are the issues that still remain in the realm of the art of medicine right now and not the science.
　　《国际循环》：为获得这些数据，我们正在做哪些努力？
　　Dr Kandzari：目前有多项试验比较双联抗血小板治疗不同疗程的结果。不幸的是，虽然这些试验中的多数是随机化试验，走上了正确的方向，但其中多数统计效能却不足。事实上，唯一的超过20 000例受试者的大型试验被设计用来比较12个月和30个月疗程的结果，但我认为广大社区医生最需要的是评价6个月和更短疗程的对比。最重要的临床问题不是能否停掉所有患者的双联抗血小板药物，而是对选择性的患者停药是否安全。由于所有药物均存在个体间变异性，而DAPT可能对特定类型的DES而非一类DES存在专一的疗效反应，因此识别出那些可缩短DAPT疗程的患者具有实际意义。这是当前医药领域仍然存在的问题。