[CIT2015]生物可降解支架的由来和现状--荷兰Erasmus大学Patrick W. Serruys教授专访
编者按:曾有专家描述,最理想的新一代支架的设计理念是:在介入术后的一段时间内,支架使血管得到机械性支撑,并借助洗脱出的药物,防治再狭窄。之后支架即缓慢降解,并完全被组织吸收,血管结构以及舒缩功能完全恢复自然状态,由此避免相关的潜在风险。生物可降解支架的出现实现了这一设想,堪称介入领域的第四次革命。在CIT 2015现场,《国际循环》采访到荷兰Erasmus大学Patrick W. Serruys教授,请他介绍这类新型支架的由来和现状。
International Circulation: Bioabsorbable stents can be called as the new milestone in the history of PCI, but it is at the beginning of development. How large is the gap between BRS data and it’s theory building in your opinion?
《国际循环》:生物可吸收支架堪称介入史上的新里程碑,但仍处于起步阶段。目前已有少数支架在临床使用,您认为当前生物可吸收支架数据与理论构建还有多少差距?
Dr. Serruys: This is a very long story. The first metallic stent was implanted in 1986 and of course we had no choice. If you want to scaffold something that has been disrupted by the balloon, the only medical device that we had was the stent made from steel. Of course, I do not believe that we need so much force to treat and heal a dissection. Since that time, in 1988 we were thinking about something less solid and less powerful than metal. We were thinking that polymer would disappear after the job has been done and it took a long time. In 1992 we had a biostable scaffold, then came along research for the polymer in 1996 to 1997 and then came the first Igaki Tamai, the first Japanese biodegradable scaffold but it was far from being perfect so it was only in 2006 that we have seen the new developments, initially with Absorb from Abbott in their first generation and the second generation. The idea is the whole phenomenon of restenosis is a short phenomenon. It only takes 6 months, the negative remodeling and the neointimal hyperplasia, so we do not see why we should put the permanent endoluminal proteases for something that is transient. Now the second point when you have put that cage of metal in the coronary arteries, it is forever. For that reason the vessel cannot bend, it cannot be expanded, there is no more cyclic strains so the whole biology of the vessel is permanently disturbed by this cage of metal. That is the reason why we want to have polymer or something which disappear. Now in 2014 and 2015, you have to think how we are still working on the first generation, where the profile is too high, the thickness of the struts is too high, but knowing what is in the pipeline I can guarantee that by the end of the decade, a great deal of metal will have been replaced by the biodegradable scaffold.
Serruys教授:这是一个很长的故事。1986年首个金属支架被置入使用,那时候没有别的选择只能使用金属支架。当时,要想支撑起被球囊破坏的血管结构唯一可用的医疗设备就是钢支架。当然,我认为治疗和治愈夹层时并不需要太大的力量。1988年我们开始思索有没有与金属相比坚硬度及强度相对更低的支架。鉴于聚合物在发挥其作用后需要很长时间才能消失,1992年我们开始拥有了生物稳定型支架,1996~1997年对支架聚合物进行了研究,研发了日本首个生物可降解支架Igaki-Tamai支架。不过该支架并不是非常完美,后来2006年生物可降解支架领域有了新的发展,雅培公司研发了其第一代及第二代生物可降解支架。其理念源于我们认为再狭窄这个现象是一个短期现象,支架只需要应用六个月即可预防负性重构及内膜增生。因此,为预防短暂的问题,我们没有理由应用永久腔内治疗用蛋白酶。其次,将金属支架置入冠状动脉后,其会永久存在。这样血管就无法弯曲,无法扩张,不能进行更多周期性应变,因而血管的整个生物学功能就被金属支架永久性地打乱了。正是因为如此,我们希望能够研发可消失的聚合物或是其他东西。2014~2015年,我们一直努力在对第一代生物可降解支架进行完善,因为其支架截面尺寸太大、支架过厚。我相信十年后,生物可降解支架将替代现有的大量金属支架。
International Circulation: According to recent clinical trials and practices, who are the indications of BRS, and is there any relative contraindications?
《国际循环》:以目前的临床试验和实践来看,哪些是生物可吸收支架的适宜人群,目前存在哪些应用上的相对禁忌?
Dr. Serruys: Yeah there is an indication and opposition. It is clear that today we still do not know the exact indication for that therapy. There are individuals saying that we should use in young patients, to avoid as long as possible, the metal in their coronaries. That is quite a small niche. There are excellent results in total chronic occlusion. This is a surprise. There are pretty good results in acute myocardial infarction, that was also unexpected. Clearly some of us use the device to reconstruct a vessel, which has been completely devastated by the disease. It is very difficult to say what are the correct indications, that will take years and then long term follow up to see if that device in these different indications can resist the test of time.
Serruys教授:生物可降解支架的应用既有适应证也有禁忌证。很显然,直到今天,我们仍然不知道其确切的适应证有哪些。有一小部分人认为,我们应在年轻患者中应用生物可降解支架,从而尽可能长时间地避免金属在其冠状动脉的存留。就慢性闭塞病变而言,应用生物可降解支架能获得较好的结局,这一点是非常令人惊喜的。此外,出乎我们的意料,生物可降解支架在急性心肌梗死患者中应用也能获得相当不错的结果。当然,也有人会应用生物可降解支架对已经被完全摧毁的血管进行重建。目前,我们很难说清生物可降解支架的正确适应证有哪些。真正要想明确这一问题,我们可能需要花费数年甚至更长时间来进行随访以确定生物可降解支架的上述适应证能否经得起时间的考验。