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[AHA2011]AHA执行主席Elliott Antman教授谈大会亮点与解析最新临床试验
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 编辑:国际循环网 时间:2011/11/21 11:32:32 关键字:AHA2011 Elliott Antman SATURN试验 PCI TRITON-TIMI 38 

    Elliott Antman   美国哈佛医学院

    <International Circulation>: As Chairman of the 2011 AHA Meeting, what has been the most exciting part of this meeting and what have proven to be the most successful points?

  《国际循环》:作为2011年AHA会议的主席,本次会议最让人振奋的是什么?已被证明最成功的观点是什么?
    Prof Antman: This was a very exciting five day meeting. We had attendees from over one hundred countries including China, and we had five late-breaking clinical trials sessions with twenty-one late-breaking clinical trials dealing with a range of topics: new drugs for preventing clotting disorders in the coronary arteries and venous circulation; some of the new anti-platelet agents, vorapaxar for example but unfortunately without a successful result in that trial; others were more successful, a very low dose of the anticoagulant rivaroxaban turned out to be helpful in preventing ischemic events in patients with an acute coronary syndrome and actually also even reduced mortality. We had an interesting report that if you eliminated the copay from medications, you can actually improve patient compliance with prescribed regimens after a myocardial infarction and there appeared to be a reduction in events depending on how you looked at it. If you had a composite endpoint that was both ischemic events and revascularization there was a trend in favor of the group who had their medications for free. If you took revascularization out, there was a statistically significant reduction favoring the no copay group. We have just learned that the insurance company that sponsored that study in the United States is going to offer post-infarction medications free on the basis of that study’s results as published in the New England Journal of Medicine, the Post-MI FREEE study. We had other reports about antiarrhythmic drugs such as the PALLAS trial looking at the powerful antiarrhythmic drug dronedarone. There was some controversy when dronedarone was approved by the FDA. Here it was reported that in patients with permanent atrial fibrillation in the PALLAS study, that dronedarone did almost everything wrong; there was increased heart failure, increased hospitalization for heart failure, increased mortality. There was a very serious consideration about dronedarone, in fact there were some powerful statements saying it should not be used anymore in patients with permanent atrial fibrillation. Then we had a clinical trial session that looked at prevention of ischemic heart disease. I was very impressed with the report on how to help patients lose weight and maintain their weight loss; this was the POWER study. This was sponsored by our National Heart Lung and Blood Institute and what I learned from that study was that you don’t have to have face-to-face interaction with the patient who is trying to lose weight. They were able to build a system of behavioral modification that utilized the available digital technology such as the internet. We did hear the SATURN trial report which was not an outcome study but provided information from an IVUS analysis of the plaque volume in patients who were treated with powerful doses of rosuvastatin and atorvastatin. The bottom line of that study was that both of those drugs showed that there was some regression of atherosclerosis and did it to about the same degree. It was not an outcomes study so we can’t really say if one drug is better than the other in terms of preventing events but at least it says to us that when atorvastatin goes generic in a couple of weeks in the United States, clinicians are unlikely to be withholding something potentially helpful for their patients by not offering the prescription drug rosuvastatin sold in the United States as Crestor. We also heard from the AIM-HIGH investigators that it is a little bit unclear as to whether raising HDL is something that can be accomplished or should be accomplished. Their study was stopped on the basis of futility; they had patients on statins who were given either extended release niacin or placebo and there was really no obvious benefit seen in giving extended release niacin. It’s a little unclear as to whether that is because the trial was underpowered, whether extended release niacin itself doesn’t work or raising HDL is just not an important thing for us to do. The whole question about raising HDL is not answered and we heard a new interesting report about a CETP inhibitor, evacetrapib, a dose ranging study which told us that it is very powerful for raising HDL. Things that we are going to have to keep our eye on about HDL include mechanistic information: should we be focusing on the number of HDL particles, HDL particle size or the functionality of HDL particles. We are actually awaiting long-term outcome studies for these CETP inhibitors and we would expect to see those in a couple of years. Then we had a very interesting report on how you would manage a patient who has genetic variation in their ability to respond to clopidogrel. This was the ELEVATE-TIMI 56 study that genotyped patients receiving the standard maintenance dose of clopidogrel of 75mg/day. Those individuals who had one copy of the CYP2C19*2 allele required three times the usual maintenance dose of clopidogrel to achieve the same level of inhibition of platelet aggregation as the wild-type patients and it was not possible to accomplish that even with a many-fold increase in the maintenance dose in patients who were homozygous for CYP2C19*2 . We had a number of other interesting sessions throughout the five days aside from the late-breaking trials sessions. What will the coronary care unit look like in fifty years? How should we think about developing cardiovascular therapeutics for the 21st century? There were very interesting discussions in that regard, thinking about systems biology not just the simple lock-and-key concept that we are so familiar with where you have a receptor and a drug that sits inside that receptor. We had a great Distinguished Scientist Lecture from Dr Roberto Bolli who also incidentally had a paper published on his SCIPIO trial results which looked at individuals who had had a myocardial infarction and he gave them cardiac stem cells several weeks after they had bypass surgery and there was a dramatic increase in ejection fraction and decrease in scar size and shrinkage of left ventricular volume compared to the group who did not get cardiac stem cells. It’s a small report, only twenty patients or less, but a very exciting result. 

    Antman教授: 这是一个为期五天的令人振奋的会议。我们 的与会者来自一百多个国家,其中包括来自中国的参会者。我们有5个最新的临床试验峰会,涉及21个最新的临床试验,解决了一系列的议题:预防冠脉和静脉循环凝血障碍的新药物;一些新的抗血小板药物,比如vorapaxar,但是它在试验中并未得到成功的结果;还有其他更成功的例子,比如利伐沙班,很低剂量就可以有助于预防急性冠脉综合征患者的缺血性事件,实际上也可以降低死亡率。我们有一个很有趣的报道,即如果取消药物的医保费用,你就能提高心梗后患者对处方的依从性,并且似乎存在事件发生的减少,后者依赖于你如何看待它。如果你有一个复合终点即缺血性事件和血运重建,就存在一个赞成免费药物的趋势。如果不考虑血运重建,非医保人群的支持率存在一个统计学意义的降低。我们刚刚得知发起该研究的美国保险公司打算提供心梗后的药物治疗,后者是基于发表在新英格兰医学杂志上的Post-MI FREEE的研究数据。我们还有其他有关抗心律失常药物的报告,例如观察研究决奈达隆的PALLAS试验。当决奈达隆被FDA批准时存在一些争议。据PALLAS研究中持续性房颤患者的报告,决奈达隆结果不佳,它能增加心衰发生率、增加心衰患者的住院率,增加死亡率。人们开始慎重考虑决奈达隆的应用,事实上有强有力的言论指出决奈达隆不应该再用于永久性房颤的治疗。我们还有一个观察预防缺血性心脏病的峰会。我对于如何帮助患者减肥或者减肥后体重的维持这方面的报告印象深刻,即POWER研究。该项研究由国家心肺和血液研究所倡议发起,我从该研究中了解到你不必与试图减肥的患者进行面对面的互动。他们能利用有效的数字技术如互联网以建立一个行为矫正系统。我们听了SATURN试验研究的报告,它不是一个结局研究,对于接受强化剂量的瑞伐他汀和阿托伐他汀的患者提供了其斑块体积的IVUS(血管内超声)信息。研究的基线是上述药物都显示有动脉硬化的减轻而且其程度几乎一样。这不是一个结局研究,因此我们并能说在预防事件发生方面一种药物优于另一种药物,但是至少它告诉我们当阿托伐他汀在未来几周内在美国应用越来越普遍时,临床医生不可能拒绝在他们的病人中应用具有潜在效用的药物,即不提供在美国以Cresor形式出售的处方药瑞伐他汀。我们还听取了AIM-HIGH研究人员的报告,有关是否提高HDL是能完成的或者应该完成的仍然有一点不清楚。他们的研究因徒劳无功而停止;他们给予接受他汀类药物的患者服用缓释类烟酸或安慰剂,结果证实服用缓释类烟酸事实上并没有明显的获益。有一点也不明确,即是否是因为该试验动力不足,是否缓释类烟酸本身并没有起作用或升高HDL对我们来说并不是一件重要的事情。关于提高高密度脂蛋白的整个问题没有得到回答,我们听到了一个新的有趣的报告,它是有关CETP抑制剂即 evacetrapib的 ,一个剂量范围研究告诉我们,它有很强大的提高高密度脂蛋白的作用。将来我们需要关注的HDL的内容包括机制方面的信息:我应该关注HDL颗粒,HDL颗粒的大小或HDL颗粒的功能。实际上,我们在等待这些CETP抑制剂的长期的研究结果,希望在未来几年内我们能看到该结果。然后我们还有一个有趣的报告,即如何处理拥有对氯吡格雷反应性相关的变异基因的病人。这也就是ELEVATE-TIMI 56研究。该研究内容是不同基因型的患者服用氯吡格雷的标准维持剂量75mg/天。那些拥有CYP2C19*2等位基因的患者需要3倍于平时的氯吡格雷的维持剂量以达到与野生型患者相同水平的抑制血小板聚集的作用,而且对于纯合子的CYP2C19*2患者来说,即使是维持剂量的许多倍,也不能达到上述效果。这5天中除了最新的试验峰会之外,我们有许多其他的峰会,五十多年后冠心病监护病房将会成为什么样子?我们应该思考如何发展21世纪的心血管疾病的治疗?在这方面有许多有趣的讨论,思考系统生物学决不仅仅是简单的锁与钥匙的理念,正如我们熟悉的哪里有受体,以及受体对药物的作用部位。我们听取了来自Dr Roberto Bolli的一个伟大的杰出的科学家讲座,顺便说一句,他发表了一篇有关SCIPIO试验结果的论文,该研究是观察研究曾经有过心肌梗死的患者,在其冠脉搭桥术后几周给予心脏干细胞治疗,与未接受干细胞治疗的患者相比,接受干细胞治疗的患者的射血分数显著升高,疤痕面积缩小,左室容积缩小。这是一个小的报告,只有20例患者或者更少,但是结果却非常令人兴奋。



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