Gregg W. Stone教授专访:从临床实践看COURAGE研究和SYNTAX研究
Gregg W. Stone教授:低分子量肝素对预防原发性或继发性,优于一次性肝素。对需要强化治疗的静脉血栓栓塞疾病患者,Fondaparinux是个理想选择。 George Dangas教授:在易出血体质患者,若需抗凝治疗数天,每天1次皮下注射制剂Fondaparinux是个不错的选择。同时,若需紧急行冠状动脉造影或者冠状动脉血运重建或置入支架,比伐卢定是个很好的选择;达成平衡很关键,把患者分层为出血高风险组、心脏病高发人群、卒中高发人群有利于临床决策。
International Circulation: The first thing I’d like to ask you today is, PCI can reduce the mortality and incidence for ACS patients but there is still no evidence in patients with stable coronary artery disease. The COURAGE Trial suggests that clinicians are perhaps a bit overly optimistic about potential outcome benefits of PCI and maybe a little over pessimistic about medical management. First perhaps you agree or don’t agree with that statement? What do you think about the results of the COURAGE Trial?
《国际循环》: PCI可以减少ACS患者的死亡率和发病率,但是在稳定性冠心病PCI使用无证据。COURAGE研究表明,临床医师对PCI带来的益处有所高估,而对传统药物疗效有所贬低。您同意还是反对COURAGE研究的这种说法?您怎么解读COURAGE研究的结论?
Prof. Stone: I think it is a very important study and one of the first that has looked at stable coronary artery disease. The important thing to realize about COURAGE is that they enrolled a relatively low-risk patient population with very stable coronary disease after screening with coronary angiography. So all the high-risk patients, the ones who really needed revascularization, pretty much got filtered out.
That being said, I think COURAGE was revealing because it showed no difference in death from myocardial infarction between very good medical therapy and medical therapy plus PCI. That is pretty much what we actually expected to find. But I think COURAGE is even more revealing when you start looking at the sub-studies of COURAGE, in particular the nuclear cardiology sub-study that looked at the amount of ischemia that patients had. In the patients that had a lot of ischemia, ischemia was very strongly related to subsequent death of MI, and PCI did a significantly better job than medical therapy at reducing ischemia. Suggesting those patients would benefit by revascularization. All the patients benefited in terms of less angina, less need for anti-anginal medication for at least a three-year period, and a better quality of life.
Although, again, with the low-risk patients they enrolled, the differences were somewhat less than had been noted previously. I think if we select our patients right, those with a significant amount of ischemia and/or a significant amount of anginal symptoms, than PCI will be of significant benefit. For patients without much ischemia or are asymptomatic, or have good quality of life with minimal angina, then I fully support medical therapy as a first approach.
Gregg W. Stone教授:COURAGE研究是一项很重要的研究,也是首个关注稳定性冠心病的研究之一。但是有一个关键点要指出,COURAGE研究纳入的人群经冠状动脉造影证实为稳定性冠心病,总体人群风险偏低。所有需要行血管再通治疗的患者大都被排除在外了。
COURAGE研究结果表明,严格药物治疗组与药物治疗和PCI联合治疗组相比,心肌梗死死亡率相同;也是我们预料之内的。但同时COURAGE亚组研究核医学方法使得心肌显象,计算患者心绞痛次数。心绞痛频繁患者其发作次数与死于心梗明显相关;PCI比传统药物治疗更好得减少了心绞痛发作;提示这些患者可从PCI血管重建中受益:心绞痛次数减少;至少3年内抗心绞痛药物需要量减少;生活质量提高。
但是,在低风险患者,两组间差别不象原来认为的那么大。若纳入患者更正确些,那些心绞痛发作频繁和/或心绞痛症状明显的患者,会大大从PCI治疗中受益。而对那些心绞痛发作不频繁或无症状或不影响生活质量的患者,药物治疗是第一选择。
International Circulation: So it was really, partially, the selection of patients for the trial that somewhat influenced medical therapy. Had it been a more high-risk group, then maybe it would have favored PCI a bit more?
《国际循环》:真的是,患者选择部分影响了研究结论。若在一组高风险人群中分析,结论会更有利于PCI治疗组?
Prof. Stone: That’s exactly right.
Greg W. Stone教授:绝对是这样的。
International Circulation: Do you think those results will or will not affect clinical practice?
《国际循环》:您认为,这些结论会不会影响到临床实践?
Prof. Stone: I think they do and they have. A lot of physicians, generalists, internists, and even some general cardiologists who haven’t read the data carefully have extrapolated COURAGE to mean you can treat patients with stable coronary artery disease without even doing an angiogram.
The have seen some anecdotal disasters by even doing that. Some patients who clearly had a lot of ischemia that they tried to manage who ended up with large heart attacks or even worse. They are also finding that you can’t manage patients with a lot of angina just with medical therapy.
It is worth pointing out in the COURAGE Trail that by having frequent follow-up visits and giving free medical care, the adherence to medical therapy was better than we had seen in any other medical study. I don’t know if that is always achievable in the real world. So we ought to strive for that. I also think that the PCI rates have now crept up again and have begun to increase. Where they took a little dip after COURAGE, and now they have increased again, appropriately so, because physicians are saying patients who have significant angina or ischemia need to have angiography to delineate the coronary arteries and revascularization when appropriate.
Gregg W. Stone教授::会的,而且已经影响到了。许多内科医生、全科医生、实习生和一些心内科医生虽没有看过这些研究的结果,已经把COURAGE所提倡的治疗方法应用于临床了:治疗稳定性心绞痛,甚至无需行冠状动脉造影。
单纯药物治疗冠心病,亦有些悲剧发生。一些患者反复心绞痛发作,虽经全力抢救,最后还是发生大面积心梗或者更糟的情况。他们逐渐意识到单纯靠药物无法治愈频发心绞痛的患者。
值得指出的是,COURAGE研究不断的随访和免费提供药品,使得其研究中药物治疗依从性好过任何以往的其他研究。不知道在临床治疗中能否达到这样的效果;我们应该朝这个方向努力。PCI手术率现在重新开始攀升,大概因为医生重新开始提倡:必要时,应对明显心绞痛患者行冠脉造影并行血管再通。
International Circulation: I think there could be a danger with some of these trials where people get a bit dogmatic perhaps, and say; ‘I’m an interventionalist,’ ‘I’m a surgeon,’ or ‘I favor medical therapy.’ Like with SYNTAX, you have people who say CABG versus PCI, and some of those other results. So, how do you think we can look at these trials fairly even handedly, without being influenced by the ‘you’re an interventionalist and I’m a surgeon,’ and work together for a team approach?
《国际循环》:本人以为若医生自身比较教条,可能会说:“我是介入手术者;”“我是外科医生;”或“我喜欢内科药物治疗;”。象SYNTAX研究中那样,CABG和PCI治疗效果的比较。您怎么看,人们如何能比较公正得看待这些研究结论;不受“你是介入手术者,我是外科医生”想法的影响。
Prof. Stone: It’s a great question. Number one we are patient caregivers. When you look at these strategy trials, it is too naïve or simple to think that you are going to get good with good therapies today that are going to clearly say that everyone should get strategy number one, or everyone should get strategy number two. SYNTAX has been misinterpreted in that way, COURAGE has been misinterpreted in that way, and frankly, these trials are going to do more harm than good if that is the take-home message. What we have to do is get the overall picture of a study and do a more nuanced look so as to point in which direction patients should get medical therapy. I also think that COURAGE also shows which patients should get PCI.
Similarly, SYNTAX identifies new patients who should get intervention, get, with relatively simple left main coronary disease which we haven’t touched in the