Dacid E. kandzari， MD.：美国加利福尼亚斯克里普斯临床中心介入心脏病学研究所所长。
International Circulation: What is the effect of drug-eluting balloons in preventing events in long-term follow-up? Is there a necessity for high-risk patients to use drug-eluting balloons?
Dr Kandzari: Today in the United States we do not have drug-eluting balloons approved for use in either coronary or peripheral interventions. But more widely speaking， it is important to recognize that drug-eluting balloons have been principally studied for lower extremity revascularization and we have (albeit emerging) still less data for their use in coronary interventions. Plausibly there are a number of opportunities for drug-eluting balloons particularly in high-risk patients – patients with very extensive， diffuse multivessel disease in which stent implantation could result in extensive stent length – and the other opportunity would be in bifurcations especially in instant restenosis situations. One of the considerations for the use of drug-eluting balloons in these high-risk patients however would also be the potential for drug-drug interactions. Most drug-eluting balloons to date， but not all， utilize the drug paclitaxel. Many of our drug-eluting stents utilize everolimus， sirolimus， and zotarolimus alternative drugs. The potential for drug-drug interaction or the potential for using a paclitaxel-eluting balloon， for example， for the treatment of a drug-eluting stent with a permanent polymer， are safety issues that still remain outstanding. All together we have very limited data with regard to the late-term use of drug-eluting balloons， their late-term efficacy and sustainability for avoiding adverse events. I think， to be sure， there is a great deal of promise and opportunity for them.
《国际循环》：药物洗脱球囊预防不良事件的远期效果如何？对高危患者是否有必要使用药物洗脱球囊？
Dr Kandzari：目前在美国，药物洗脱球囊尚未获得批准用于冠状动脉和外周血管的介入治疗。从更广泛的角度来说，我们必须认识到，药物洗脱球囊最初是在下肢血运重建领域进行研究的，（尽管已经开始）在冠状动脉介入中的应用资料还非常少。但我们相信在高危患者中有许多机会用到药物洗脱球囊——如非常广泛、弥散的多支血管病变，如全部置入支架将导致支架过长——其他如分叉病变、尤其是再狭窄的情况下。在使用药物洗脱球囊时必须考虑的问题之一是，这些高危患者存在发生药物-药物相互作用的潜在可能。截至目前，多数药物洗脱球囊使用的是紫杉醇。我们使用的许多药物洗脱球囊携载了依维莫司、西罗莫司和佐他莫司等替代药物。例如，在治疗永久性聚合物药物洗脱支架置入后再狭窄的病例时，就存在药物间相互作用的可能性，这是目前仍然十分突出的安全性问题。总之，对于药物洗脱球囊的晚期使用，以及其预防不良事件的晚期有效性和可持续性，我们目前的资料还很少。但我确信，药物洗脱球囊有很好的应用前景和机会。
International Circulation: There is still a concern of thrombosis risk with DES in STEMI patients. Do you think DES should be the first choice for STEMI patients?
Dr Kandzari: We should recognize that no matter what type of stent we use， whether it be a drug-eluting stent or a bare-metal stent， ST-elevation myocardial infarction， and probably only paralleled by chronic kidney disease and to a lesser extent diabetes， are the three biggest risk factors for stent thrombosis. As we have seen in trials like HORIZONS through long-term follow-up comparing a bare-metal stent versus a paclitaxel-eluting stent， not only do the outcomes of stent thrombosis not statistically differ between the two stent types， but the event rates are high again no matter what type of stent we use. With that background， I think the use of a drug-eluting stent has not only proven efficacious in avoiding repeat revascularization but relative to bare metal stents， it has proven fairly safe. There are even more recent contemporary data that are a little more hypothesis-generating rather than conclusive， but they seem to suggest that drug-eluting stents， at least for selective DES， have a potential advantage and even a safety outcome as well. For the broader use of drug-eluting stents however， one of the challenges of treating patients with STEMI is that there is little opportunity for discussion between the doctor and the patient regarding other comorbidities， regarding the need for forthcoming unplanned surgeries， regarding the adherence or opportunity for compliance or adherence to dual antiplatelet therapy. These are some of the challenges in a broad blanket conclusion to using drug-eluting stents in all ST-elevation myocardial infarction patients. Maybe our best step forward is from the HORIZONS trial， which applies a very simple model or scoring system for lesion length， for the vessel diameter and for the presence or absence of diabetes， and if the patients score especially with all three of these variables (i.e. they have a small vessel， a long lesion and they are diabetic) clearly the relative advantage of a drug-eluting stent and avoiding repeat revascularization is going to be even greater. There is a still a bit of individualized therapy for the selection of drug-eluting stents. As a general standard of care， I think the data is fairly sufficient to support that.
《国际循环》：对于DES治疗STEMI患者，仍有很多学者担心起血栓形成的风险。您认为应将DES视为STEMI患者的第一选择吗？
Dr Kandzari：我们应认识到，不论使用哪种支架，不论是药物洗脱支架还是裸金属支架，ST段抬高心肌梗死和慢性肾脏疾病以及糖尿病，是支架内血栓形成的3个最主要的危险因素。正如我们在HORIZONS等临床试验中所看到的，裸金属支架和紫杉醇洗脱支架的长期随访结果对比显示，不仅支架内血栓形成的发生率没有统计学差异，而且其他事件发生率也与所使用的支架类型无关。鉴于这种背景，我认为药物洗脱支架并未被证明比裸金属支架能够更有效地预防再次血运重建；并且与裸金属支架相比，其安全性也是相同的。近期研究的一些短期数据与其说是结论，不如说是更偏向于来自理论上的推断：这些数据似乎提示药物洗脱支架，尤其是特定类型的DES，安全性与裸金属支架相似，而疗效似乎更有优势。至于更广泛地使用DES治疗STEMI或者，主要的挑战在于医生和患者很少有机会去充分讨论关于患者的其他合并症、未来不确定的外科手术、治疗依从性或对双联抗血小板治疗的坚持程度等问题。这些是对所有STEMI患者均使用DES的问题作出结论前存在的一些挑战。我们向前迈进的最好依据可能是来自HORIZONS试验的启示，该研究使用了一种非常简单的模型或评分系统，该系统包含病变长度、血管直径和有无糖尿病，如果1例患者的评分涵盖了所有3项参数（即血管细小、长病变、合并糖尿病），那么显然置入DES及其预防再次血运重建的相对优势可能更大。还有一些支持选择DES的个体化疗法。作为总的治疗原则，我认为目前的数据足以支持上述观点。
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。
[下一页] [1] [2]