不断更新技能与知识 介入心脏病学终身教育

    循证医学： Xience V相关临床试验与 PROSPECT进展

    Dr Stone具有丰富的临床试验经历，如新一代支架 XIENCE V的系列研究，在 CCHeart邮件采访中他提到， XIENCE V支架与前代支架相比改善显著，设计方面克服了既有支架的许多缺点。试验结果被 COMPARE单中心随机试验重复。

    PROSPECT试验是评价易损斑块自然病史的研究， 700例ACS患者罪犯病变成功置入支架后，对其他冠脉进行造影、灰阶 IVUS和虚拟组织学 IVUS分析。研究发现，非罪犯病变未接受支架置入的血管未来发生事件的预测因素包括： 1）严重狭窄——最小管腔面积小于 4mm²；2）斑块负荷大于 70%；3）虚拟组织学 IVUS发现薄帽纤维粥样硬化。

    左主干病变介入治疗的发展

    左主干血管成形术的发展是一个颇具波折的过程，最初的球囊成形术使患者经常发生再狭窄导致猝死，后来裸金属支架的应用效果稍好，但再狭窄率仍然高，现在药物洗脱支架似乎使大家看到了曙光。 SYNTAX试验的结果使得适应证有所放宽，允许医生进行相对简单类型的左主干病变置入药物洗脱支架，但我们觉得适应证的水平应高于外科，所以我们设计了 EXCEL随机试验，入选 2500例无保护左主干病变轻度和中度复杂冠脉解剖的患者。试验将于数月后开始，我们对此很期待。

    对中国临床试验事业发展的建议

    非常高兴地看到中国的发展，首先，中国冠心病病例非常多；其次，医生的技术以及政府的努力使得冠心病患者能够有效地得到治疗，尤其是通过冠脉介入治疗；第三，我们看到中国的高质量随机对照临床试验越来越多，我们与 CCRF的合作非常愉快， CCRF未来将开展高质量随机试验。总体上，我对于中国未来临床试验的发展非常乐观，中国受过训练的医生数量增加，介入水平也比 5年前有大幅提高，还将继续提高。我们对于未来与中国合作发展高质量医疗非常感兴趣。

    TCT2010亮点

    TCT2010将是我们历来最全面、最有创意的教育盛会，包括大量重要临床试验结果的发布，这些试验包括外周血管疾病、结构性心脏病、药物洗脱支架、急性心肌梗死和辅助药物治疗。 TCT前两天包括近 20场学术研讨会，涵盖介入心脏病学各个亚学科不同领域，进行深度、最新、全面的评述与讨论，后三天将在主会场、冠心病会场和结构与外周会场进行手术病例转播。口头和壁报交流将用一整个下午进行。此外， TCT期间还有 FDA市政厅会议、晚间讨论会、暮光专场、厂商早餐会和其他创新活动。这届会议将对全世界参会医生提供令人激动的、丰盛的学术盛宴！

    美国介入培训的启示

    介入医生的培训开始很早，在学习完基础内科和心脏病学之后，医生主要在导管室学习及工作。我们每年开展很多课程，从介入心脏病学 Fellow Course开始，它教授一些基层心脏病医生了解介入心脏病学科内容。有一个手把手教学的导师对于优秀介入医生的成长是至关重要的，我们的培训贯穿整年，顶峰是 TCT， TCT吸引全球介入学界的专家、学者共同分享经验，参会者在这里学习技术以处理复杂血管介入术、结构性心脏病、外周血管疾病介入治疗；如何避免和处理并发症；获悉最新临床试验结果，指导他们在临床中更好地治疗复杂心脏病患者。所以我们觉得 TCT是每年最重要的会议，大家共聚一堂，更新技术水平和知识储备、为介入心脏病学终身教育打下基础。

    Update Skills and Knowledge for Lifelong Education in Interventional Cardiology
                                                                   ——interview with Dr. Gregg Stone

    CCheart:  You have led or participated in a lot of clinical trials that contributed to updates to guidelines and clinical practices of interventional cardiology. Can you tell us about the progress of the PROSPECT and XIENCE V study?
Dr. Gregg Stone:  Xience V refers to what we call a second-generation drug-eluting stent. It is an everolimus-eluting stent that is manufactured by Abbott and distributed by Abbott under the name Xience V and Boston Scientific under the name Promus. This stent has significant enhancements compared to earlier designs in that it is a very low-profile, flexible, cobalt chromium stent. And given that it is low profile, it tends to cause a very small amount of arterial injury and endothelializes relatively easily. It is also very conformable to the vessel wall, and it tends not to fracture. In fact, it hardly ever fractures. In addition, it is coated with a nonerodable fluoropolymer, which is very elastomeric. It is very inert and tends not to cause any excessive inflammation or hypersensitivity reaction. The polymer, of course, controls the dosing and the release kinetics of the drug, which is everolimus, and the dose of everolimus is about half that of any other limus on any other drug-eluting stent. So this stent has been designed to overcome a lot of the limitations of prior stents.

    We have investigated this stent in a series of trials called the SPIRIT trials—SPIRIT I, II, III, and now IV. Most recently we reported the results from SPIRIT IV—the largest completed head-to-head trial of 2 drug-eluting stents—in which the Xience V everolimus-eluting stent was compared to the Taxus Express paclitaxel-eluting stent in almost 3,700 randomized patients. And with follow-up now to 1 year, this trial showed reduced target lesion failure with Xience V compared to Taxus, target lesion failure being the composite endpoint of cardiac death, target vessel myocardial infarction, or ischemia-driven target lesion revascularization. There were also statistically significant reductions in both target lesion revascularization itself as well as stent thrombosis—about a 75% reduction in stent thrombosis. Myocardial infarction was also reduced with the Xience V stent.

    This very large trial, which was done without any angiographic follow-up to replicate clinical conditions in simple and moderately complex patients, showed significantly enhanced safety and efficacy with the Xience V stent compared to the paclitaxel-eluting stent. These results were duplicated in the COMPARE trial, which was a single-center, 1,800-patient randomized trial of all comers performed by Peter Smits and his colleagues in the Netherlands, which also showed that Xience V compared to Taxus—but in this instance the Taxus Liberté stent—the next-generation version of Taxus—also reduced myocardial infarction and stent thrombosis, and improved freedom from target lesion revascularization and target vessel revascularization. So in all studies now it appears as if this new-generation everolimus-eluting stent, the Xience V or Promus stent, has significantly better safety and efficacy than does the predecessor Taxus Express or Liberté stent. These results were found in all patients except for those with diabetes mellitus, in whom there were no significant differences between Taxus (either Express or Liberté) and the everolimus-eluting stent, whereas there was a marked difference in nondiabetics.

    Regarding PROSPECT, this was a natural history study in patients with acute coronary syndromes who underwent successful angioplasty, in which we performed angiography, gray-scale ultrasound, and virtual histology—that is, radiofrequency IVUS—of the remainder of the coronary tree to see if we could determine in which patients the lesions were at risk for future events. We followed about 700 so-treated patients who underwent imaging of the entire coronary tree for 3.4 years on average. And we found that in untreated coronary segments, future major adverse cardiovascular events (MACE) were predicted by, number one, severe stenoses. And that was a minimal lumen area of less than 4 mm². Now these were areas of the coronary tree that usually on angiography look normal or very mild. So grayscale ultrasound showed this, but angiography didn’t. The second predictive factor of future adverse cardiovascular events was a plaque burden of greater than 70%. Again, that’s something you can only appreciate by IVUS, not by angiography. And third, a virtual histology finding of a thin-cap fibroatheroma was also a powerful multivariable predictor of future adverse cardiovascular events, such that lesions that were thin-cap fibroatheromas had a much higher incidence of future MACE compared to lesions that did not have any sort of necrotic core, such as pathologic intimal thickening or fibrotic or fibrocalcific plaque, which were actually protected from future events.     

    CCheart:  What do you think about the development of coronary intervention for LM lesions, one of the more complex PCI procedures?

    Dr. Gregg Stone:  Left main angioplasty has had a checkered history, starting with balloon angioplasty, where patients would often restenose and have sudden cardiac death. Bare metal stents did somewhat better, although the restenosis rate was still too high. Now with drug-eluting stents, it seems as if we can see light at the end of the tunnel.

    The SYNTAX trial randomized 1,800 patients, 705 of whom had unprotected left main disease, to either Taxus drug-eluting stents or bypass surgery. And among the patients with left main coronary artery disease, there overall were similar rates of death and myocardial infarction, with somewhat lower rates of stroke with angioplasty but somewhat higher rates of target vessel revascularization. However, the results seemed to vary significantly with the Syntax Score, which is a measure of anatomic complexity on the baseline angiogram. Those patients who had either a low or intermediate Syntax Score had lower rates of death with PCI compared to CABG, similar rates of myocardial infarction, and a tendency toward lower rates of stroke with no significant increase in target vessel revascularization. On the other hand, patients who were the most complex with high Syntax Scores had significantly higher rates of mortality with Taxus drug-eluting stents and also markedly higher rates of target vessel revascularization.

    Now this is only subset data, and while the indications for left main stenting have been somewhat loosened by the results of this trial, such that they now have received a Class IIB recommendation to allow interventionalists to do left main stenting with drug-eluting stents for relatively simple types of lesions, we actually believe that the results might even be superior to surgery. So we have designed the EXCEL trial, which is going to be a 2,500-patient randomized study of unprotected left main disease in patients with simple and moderately complex coronary anatomy. And that trial will be started in several months. We’re very excited about that study.

    CCheart:  What are your recommendations on the future development of clinical trials in China?

    Dr. Gregg Stone:  We’re very excited about what we see going on in China. Number one, there is obviously a lot of coronary artery disease, as one would expect in any population as large as China’s. Number two, there is a growing commitment by physicians and by the government to be able to effectively treat coronary artery disease, especially with revascularization with percutaneous coronary intervention. With that commitment, we see an increasing number of clinical trials—high-quality, randomized, controlled trials—being done in China. We’re excited about our relationship with China Cardiovascular Research Foundation (CCRF), which will run high-quality randomized trials.

    So in summary, I’m very optimistic that there will continue to be increasing high-quality percutaneous coronary intervention done in China in an increasing number of patients. More physicians are being trained, the quality of the intervention that is being done is significantly improved now compared to 5 years ago, and it is going to continue to improve. China will very soon, within the next year if not already, be the population with the second most angioplasties performed per capita after the United States, and we’re very excited about our future partnership with China in developing high-quality care for its citizens.

    CCheart:  Could you tell us about the highlights of the TCT 2010 program?

    Dr. Gregg Stone:  TCT 2010 is going to be the most comprehensive, and ambitious program that we have yet organized and sponsored. We expect that there will be a tremendous number of very important late-breaking trials in the areas of peripheral vascular disease, structural heart disease, drug-eluting stents, acute myocardial infarction, and adjunct pharmacotherapy.

    On the first 2 days of TCT we will have approximately 20 scientific symposia, which will be in-depth, up-to-date, thorough reviews of every aspect of the multiple different facets of the subspecialty of interventional cardiology. The next 3 days will have live cases in 3 venues, that is, the main arena, the coronary theater, and the structural and endovascular theater. There will be a full afternoon dedicated to oral and poster abstract sessions. In addition, there will be FDA town hall meetings, evening symposia, special twilight sections, industry breakfasts, and multiple other new innovations that will make it very exciting and rewarding for interventionalists from all over the world to attend TCT 2010.

    CCheart:  A standardized training program for interventionalists is being implemented in China. Could you please give us an overview of your experience in interventional training in the U.S. and how the TCT program has contributed to this?

    Dr. Gregg Stone:  We believe that training as an interventional cardiologist starts very early, after the physician learns basic internal medicine and cardiology, and then continues in the cath lab for the rest of the physician’s life. We put on multiple courses throughout the year, starting with the Interventional Cardiology Fellows Course, which teaches basic cardiology fellows the science of interventional cardiology. Training hands-on with a mentor is critical to learning to become a good interventional cardiologist. And then we put on courses throughout the year, the pinnacle of which is TCT, or Transcatheter Cardiovascular Therapeutics, which brings the global interventional cardiology community together to be able to share their experiences. Attendees learn techniques to be able to deal with complex vascular interventions, structural heart disease, peripheral intervention; how to avoid and manage complications; and the latest science from clinical studies, which will allow us to take better care of our patients with complex cardiac disease. So we view TCT as an essential meeting every year where everyone gathers to update their skills and their knowledge base for lifelong education in interventional cardiology.