International Circulation: Obviously you are the pioneer and lead investigator in the drug-eluting stent field， we’d greatly appreciate your sharing your perspectives today. Have we met our expectations on the safety and efficacy of drug-eluting stents that are on the market today?

Prof. Leon: It’s a very interesting question. When we began this work， about a decade ago， we had very higher expectations. What we would call a rosy prophecy， the drug-eluting stents will eliminate restenosis， and be as safe as bare metal stents. What we’ve learned is， with the first generation of drug-eluting stents， restenosis has been dramatically reduced， but not eliminated. In still some high risk groups of patients， we still see some restenosis. But also， they were not as safe as we have predicted， and some of the early drug-eluting stents did have a problem， with a small but definite increase of very late stent thrombosis. So the early expectations were not met by the first generation of devices. But now we have new devices， we have yet even newer devices on early stage of testing that we hope will be as safe as bare metal stent， and some may be even more effective in reducing restenosis. 

International Circulation: And you’ve mentioned late catchup. So we’ve talked about late catchup of restenosis， in addition to the worries about late stent thrombosis， so what is your view on this? Are there any differences in drug-eluting stents when it comes to the long-term performance?

Prof. Leon: It’s a very good question. We don’t have a definite answer. If we look at bare metal stents， we’ve generally seen in the first five years that there is a very little increase in the frequency of restenosis after one year， that it tends to peak at one year， and then it’s very flat， very intriquing advance between years one and five. With drug-eluting stents， at least the earlier drug-eluting stents that have been followed about five years， we found about doubling of the number of patients that have restenosis between years one and five. And that change is what some people call late catchup phenomenon. We are not certain of the newer drug-eluting stents with some suggestion with the Endeavor stent that there is greater durability recently with less late catchup after year one， but we really do need larger studies with longer follow-ups to make definitive conclusions.

International Circulation: When we talk about the trials for the drug-eluting stents， what will some of the newer trials for drug-eluting stents look like? Or perhaps what should they look like? And what kind of questions are remaining for us to figure out when it comes to drug-eluting stents?

Prof. Leon: Well， this is very important， because we are entering an era what we call “mega-trials”. It used to be that we can do a clinical trial of five hundred patients， through a thousand patients， with 1500 patients， and wind all of our answers. But now we have concerns about safety， which are generally low rate phenomena， we often have to do much larger studies; and since some of the events occur not only the first year， but after the first year， we have to have longer follow-up. So the new generations of randomized trials of drug-eluting stents have to be larger with longer follow-up. An example， the PROTECT trial， which is just completed in Rome， is an 8800-patient randomized trial looking at the Endeavor versus the Cypher stent， with an effort trying to see the right differences in very late stent thrombosis. So clearly the new studies that will provide important answers have to be much larger.

International Circulatin: And PROTECT study was really looking at safety， was it? I mean the safety issue there?

Prof. Leon: But also it would deal with the issue of durability. If we saw the late catchup， for instance， with the Cypher trial， which has been suggested in earlier studies， but now with the Endeavor， we would see a clearly express of the trials such as this. 

International Circulatin: And there were some differences you mentioned in trials， like between the SORT-OUT trial， and Endeavor III， Endeavor V. So， with these larger trials， does it really help us to get that answer to the durability question when we have a larger trial?

Prof. Leon: Certainly. There is no substitute for a larger， well-conducted， randomized trial. Unfortunately， we don’t have very many of them. But some devices now have been subjected to very large studies I think will have more conclusive evidence of differences between drug-eluting stents.

Internationl Circulation: Can you give us some predictions on what is the big picture， what’s coming up in the future with drug-eluting stents or stents like others? I knew you are going to be talking in CIT about that， can you give us some insights?

Prof. Leon: Well interventional cardiology is a very dynamic and rapidly changing field， so there are many many exciting things. With respect to drug-eluting stents， I think we are still very focused on trying to improve safety， because the concern of unlimited dual antiplatelet therapy becomes very problematic around the world， so many efforts on stent implant technology to improve safety， absorbing polymers， polymer-free systems， lower doses of drugs， many different things tried magically to technology to improve safety. So that’s one area. A second area is to change the platforms of the drug-eluting stents. There are many bifurcation stent designs. There are microstents， and there are some fancies being done completely nontalent by absorbable things. And another area in interventional cardiology， obviously， there is some pretty low dynamic change. One of the most interesting and has yet found its way to Asia-Pacific or China at this time， is the whole field of transcatheter effort. Many of the earlier principles we’ve applied to interventional cardiology are now being directed to treating patients with valvular heart disease， particularly patients with valvular stenosis. 

International Circulation: And when it comes to actually adopting some of those new technologies in treatment， when it comes to valves， what will it take to really get that applied on a large scale， and really get into a large-scale clinical use?
Prof. Leon: That’s a very important question. We are in the mid step on a primitive clinical trial in the United States， which is studying over 3000 patients that are randomized between new percutaneous transcatheter therapy compared to the standard treatment， which will be， for instance， many patients on surgery， surgical valve replacement. Studies such as this， which are larger， thousand patients， are very uncommon， evaluating a heart disease， and should provide some great insights.