<International Circulation>： Are there any studies that we should keep an eye out for in the etiology and pathogenesis of stroke?

　　《国际循环网》：有是否有关于卒中病因和发病机制的研究需要我们特别关注？
Dr. Koroshetz: One is the genetic studies. There have been many studies of diseases with multiple genetic influences. We are currently funding one large study in stroke， with thousands of patients. The expectation is that the data will be related to specific stroke subtypes. That has been proved in previous work in Europe. They have seen genetic markers associated with large artery atherosclerotic stroke. We are hoping that these can be confirmed in the American studies and that also reveal genetic isoforms that can relate to the other genetic subtypes. The genetics it the biggest study now. In terms of other studies， the POINT (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke) study is currently operating in the USA and is studying DAP in TIA and minor stroke. The CREST (Carotid Revascularization Endarterectomy vs Stenting Trial) group is looking at follow-up of stenting versus endarterecomty for carotid disease. That is also an ongoing study. Some studies in hemorrhages are looking at genetic elements and risk factors that lead to intra cerebral hemorrhage in Hispanics and African Americans versus Caucasians， called the ERICH (Ethnic/Racial Variations of Intracerebral Hemorrhage) study. There are some therapeutic studies as well. One is called CLEAR (Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke)， which is looking at treating patients with intra-ventricular hemorrhage. They are being treated with catheter-removal of clot and insulation of rt-PA into the ventricles to help dissolve the clot. Another study， which reported its PhaseⅡresults at the ISC， is called MISTIE (Minimally Invasive Surgery plus Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation). This study looked at patients who bleed right into the brain itself， as opposed to the ventricles. In that study， patients are randomized to a laparoscopic catheter that is directed into a burr hole into the clot， and t-PA is instilled into the brain clot and the clot is sucked out. The PhaseⅡstudies looked incredibly promising and that group is looking to further to Phase Ⅲ study. The other big study of the meeting was for the intra-arterial stroke management. This is another acute treatment for cardioembolic stroke. Embolism usually causes the massive strokes. In the US， there has been the promulgation of catheter based therapies where a catheter is placed in the groin and guided up to the brain artery and the clot is removed with a device and t-PA. There were three studies at the stroke meeting. These three RCTs (Randomized Controlled Trials) all showed no benefit in intra-arterial therapy. That was a real shock and big disappointment. A study from Italy comparing intra-arterial therapy showed no difference; an NIH-funded study in the US took patients who failed to respond to t-PA were randomized to intra-arterial therapy versus no treatment and， in the end， showed no benefit; and another NIH study randomized patient with t-PA and intra-arterial therapy and again showed no benefit.

　　Dr. Koroshetz:说到需要关注的问题，不得不提遗传学研究。有许多关于遗传因素对疾病影响的研究。我们正资助一个大样本卒中研究，期望遗传学数据和特定卒中亚型有关。欧洲有试验证明了这一点，他们发现了与大动脉粥样硬化性卒中相关的遗传学标志物。我们希望在美国的研究也能得到证实，同时希望发现与其他卒中类型相关的遗传学方面的亚型。遗传学是目前研究热点。其他研究，POINT（Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke）研究正在美国进行，研究DAP在TIA和微小卒中中的作用。CREST（Carotid Revascularization Endarterectomy vs Stenting Trial）研究组正进行颈动脉疾病患者的支架置入和血管切开取栓后随访研究。另外还有ERICH（Ethnic/Racial Variations of Intracerebral Hemorrhage）研究，观察不同种族（西班牙人，非裔美国人和白种人）颅内出血的高危因素以及是否受遗传因素影响。当然，目前也有许多治疗性研究。其中CLEAR（Combined Approach to Lysis Utilizing Eptifibatide and rt-PA in Acute Ischemic Stroke）试验研究脑室内出血患者治疗，使用脑室内导管移除血栓，并注入rt-PA溶解血栓。MISTIE研究（Minimally Invasive Surgery plus Tissue Plasminogen Activator for Intracerebral Hemorrhage Evacuation）团队在ISC报告了第二阶段研究结果，研究选取大脑内部而非脑室出血的患者，随机分到腔镜导管组，导管通过圆孔直接插入血栓部位，沿导管灌注t-PA溶解血栓。试验结果不错，该团队正努力筹备第三阶段临床试验。会议上还有其他动脉内阻塞致卒中的大型临床研究，是颅内血管栓塞导致卒中的紧急处理方面研究。栓塞常导致大面积卒中。美国现有一种导管介入新疗法，从股动脉置入导管，到达脑动脉后通过t-PA及特定装置移除血栓。在ISC上有3项随机对照研究都表明血管内介入治疗没有明显优势。这些结果令我们非常震惊和失望。第一个来自意大利的研究结果表明介入治疗没有明显优势。第二个研究是美国NIH资助项目，研究者把t-PA治疗效果不好的患者随机分为动脉内介入治疗组和无治疗组，结果表明两组效果无明显差异。第三个试验也由NIH资助，将患者随机分为血管内介入治疗组和t-PA组，试验结果仍是两组无明显差异。

<International Circulation>：How will that change the standard of care?

　　《国际循环网》：这些试验结果会如何改变卒中医疗护理标准
Dr. Koroshetz: Most people in this field already believed this technique was going to work. These results were a surprise and emphasize the need for RCTs before generalizing to a large population. There were some clues from the studies that been performed earlier. In a large NIH trial called IMS Ⅲ (Interventional Management of Stroke Phase Ⅲ)， the earlier the patients received treatment， the better off they did. This is not surprising. It looks as though this technology has come too far along to help them. There is a need for much more trial with a much more rapid treatment for getting patients to the cath-lab. The other things we’re interested in are new generation catheters， which will remove clots more effectively and faster. These are called stent-retrievers and have come on market since these trials started.  The new studies would concentrate on these new devices with more rapid treatment.

　　Dr. Koroshetz:在卒中治疗领域许多人认为血管内介入治疗有效。这些试验结果让人吃惊，试验侧重于符合RCTs，而并没有大样本的更有说服力的试验来证明其结果的有效性。NIH资助的大型IMS（Interventional Management of Stroke Phase）Ⅲ试验发现，患者越早接受介入治疗，获益越多。这个结果并不奇怪。貌似此介入技术有点过度治疗而使患者获益较少。现在还需要更多的试验来研究如何把患者带到导管室接受更快速及时的治疗。我们还对能更快速有效移除血栓的新导管感兴趣。试验开始后，称为支架取栓器的导管就开始在医疗市场亮相。以后研究将会关注能更快治疗的新设备产生。