International Circulation: The drug eluting stent was designed to attenuate the complication of in-stent restenosis but it didn’t eliminate this problem. What are the main reasons for in-stent restenosis after DES implantation?
　　Dr. Waksman: Yes it is true that restenosis has been significantly reduced by the use of drug eluting stents but we still see about 5% of target lesion revascularization with simple lesions and with complex lesions we see them up to 10%. It is multi-factorial; there is not one single cause. For example， it could be mechanical as we have seen some stent fractures. When the stent fractures， the polymer also fractures and the drug is released and this， in itself， can induce restenosis， usually focal restenosis. There are some biological reasons. Sometimes the drug is not effective and that is also seen in oncology that not everyone is responsive to the drugs or there is some resistance to the drugs. We also see some inflammation from the polymer. Primarily in the first generation stents， we have seen that the polymer induces neointimal inflammation and this can lead to restenosis. We are also seeing recently very late restenosis which is basically complete healing which was initially delayed but there is a price to pay for that with very late restenosis. We have seen in some of the trials， a TLR rate of 24% up to 5 years. That is pretty high when you consider 25% restenosis rate is what we used to see after 6 months， but with the drug eluting stents we can see it at 4 or 5 years.