International Circulation:  You have spoken today on the topic of which recommendations can we give in 2009 with respect to drug-eluting stents.  What are the recommendations with regard to the application of drug-eluting stents?

David Holmes:  I think that it’s a complicated subject and field.  It takes into account the balancing of re-stentosis versus the balancing of late events.  Clearly re-stenosis is not a benign event.  If those patients who were treated with a bare metal stent get re-stenosis and about a third of them have an acute coronary syndrome.  Sometimes including a stemi as part of the manifestation.  So we could say that clinical restenosis is not benign.  The initial impetus to develop drug-eluting stents was to decrease re-stenosis， both clinical and angiographic rest enosis.  There is no question that that has worked.  All the studies have shown that drug-eluting stents decrease rest enosis.  The second part of that equation is the issue of stent thrombosis， which can occur with both bare metal and drug-eluting stents.  It looks like that issue has shifted a little over time with drug-eluting stents and when it occurs it is an awful problem， irrespective if it is with bare metal or drug-eluting stents.  What we know now is that there are strategies being studied to optimize the long-term outcome.  The long-term outcome with medical therapy is often now dual anti-platelet therapy.  So， it comes as no surprise， that with the implantation of stents that is also part of the process.  What we try to decide now， and is still yet being explored， is how long do you have to keep it up for?  The data would suggest that most of the events occur early on.  The second piece of information， however， is to say there are new drugs and new approaches， such as prasugrel， which will over the long-term， further decrease stent thrombosis.  But these studies and approaches are still works-in-progress as we develop better， more healing stents that combine the advantages of decreasing rest enosis while mitigating the disadvantage that is seen.  The disadvantage being small but for the patient who gets it is an awful thing.