International Circulation: The topic of one of your lectures at CIT will be， “Evidence-Based Medicine: The Most Impactful Late-Breaking Clinical Trials from TCT08. Can you give us an introduction to those late-breaking trials and their results?

Prof. Kirtane: There are two trials that I talked about the most. The first one is the HORIZONS AMI trial， which was basically the stent randomization. The backdrop to that is that there has been a lot of use of drug-eluting stents and there is controversy surrounding whether they should be used for patients with acute ST-elevation myocardial infarction (STEMI). The HORIZONS AMI trial is the largest randomized trial in that patient population， randomizing patients to the Taxus stent vs. its bare-metal comparators. The HORIZONS AMI trial was also a pharma trial and those 30 day endpoint results were presented at the prior TCT. This time， the stent randomization was the issue at hand. In that randomization， the use of the Taxus drug-eluting stent was associated with lower rates of restenosis related endpoints compared to a bare-metal stent. What is interesting is the absolute difference was not as great as some might have thought and in fact some people would argue that because that absolute difference was not that great， that many patients could be treated fine with a bare-metal stent and we can reserve the drug-eluting stent for the most complex lesions， but that is all exploratory. The main results that were presented were the presented were the rates of restenosis and hard clinical endpoints. There was no difference at one year between the two stents in terms of the overall mortality.

The second trial is the SYNTAX trial， which was initially presented at ESC， but there was a lot of additional data presented at TCT; in particular， involving the left main subgroup， the multivessel subgroup， and so on. Essentially， what the results showed is that in appropriately selected patients you can get similar rates of death and myocardial infarction with drug-eluting stenting compared to coronary artery bypass surgery. There is actually a slight decrease in stroke with bypass surgery compared to stents and there is an improvement in terms of rates of repeat revascularizations with surgery compared to drug-eluting stents. You have to treat 14 patients to prevent a repeat revascularization. Overall， the trade-off is one that many patients would take in terms of preferring stents over surgery.

The other thing about SYNTAX that we saw was the use of the SYNTAX score， which is a good way to risk stratify patients. Patients with high SYNTAX scores would benefit more from surgery than those with low scores who would probably do well with either approach. Those are two of the biggest trials I will talk about.

International Circulation: How do you think the results of SYNTAX will translate into clinical practice?

Prof. Kirtane: I think that we need to first look at longer term data because to look at a combined endpoint of death and M.I. at one year is reassuring for stenting but you want to see that it is maintained through longer follow-up. Most of the prior data in surgery vs. stenting shows that the overall rates over time are similar， but we need to make sure that is the case with SYNTAX. Otherwise， I think it just reinforces the fact that when you have patients with complex multivessel disease and/or left main disease there are a variety of options and it seems that either option is reasonable based on the results of SYNTAX and either option has risks and benefits. For surgery the upfront risk is slightly greater—greater stroke. I personally believe， although the SYNTAX results didn’t show it， that there is an upfront greater mortality risk with surgery compared to angioplasty. That is the conventional thinking that if you go for an open CABG procedure you are going to have higher mortality. Why that wasn’t seen in SYNTAX I don’t know， but that is the tradeoff with surgery. The tradeoff with stents are clearly repeat revascularization procedures， but most of my patients， if they would have to trade a repeat revascularization vs. a surgery， they would prefer a repeat revascularization.

International Circulation: What is the principle of management of PCI procedures for CAD patients with recurrent heart failure? For those patients who have a history of old myocardial infarction how should they be handled?

Prof. Kirtane: I think there is limited data in terms of the management of patients with low ejection fraction or heart failure and concurrent coronary disease. That having been said， the patients with low ejection fraction are some of the highest risk patients that we see and therefore it goes without saying that they would probably benefit the most if they have significant ischemia and revascularization of ischemic territories is paramount. I think is true for revascularization in general. The role of PCI vs. surgery is dependent on the patient and I would use clinical judgment for one vs. the other.

In terms of patients with old myocardial infarction， the same thing applies. If you have M.I. your ejection fraction is not going to be normal and so we try to maximize perfusion of other territories to prevent further bad things from happening to the patient.

Some people have tried to apply the data from the COURAGE study to these two patient populations. In general， I think it is difficult because the average ejection fraction in the COURAGE trial was 60% or greater. I think this just reinforces the fact that we have limited data to inform our decision making in these patient populations. It seems to me that if you have ischemia these people will benefit even more than patients with normal ejection fractions or no prior myocardial infarctions.

International Circulation: What do you think the future of DES will be?

Prof. Kirtane: I there is obviously a lot of excitement about polymer-free systems or ways to get rid of the polymer because there is some thought that the polymer is causing some of the inflammatory response that may result in the adverse effects of DES. There has also been some interest in bioabsorbable drug-eluting stents， but the problem with those is that typically the entire stent is a polymer so the questions of if they have more inflammatory reactions and if they have enough radial strength remain unanswered at this time.

International Circulation: You have spoken about balancing safety and efficacy of drug-eluting stents. Where will we see the greatest advances coming up in the future? Will it be in safety or efficacy?

Prof. Kirtane: I think efficacy at this point is going to be difficult to improve on because such strides were made between the introduction of drug-eluting stents， but that doesn’t mean there can’t be further improvement. There are certainly patients who restenose so that is something to work upon. I think a lot of the focus now， appropriately so， is looking at the safety side. We don’t want patients to thrombose and there are things that we can do when we do the procedure itself to make sure the stent is well apposed， to make sure it is well expanded， and make sure the antiplatelet regimen is ok， but I think there is still the issue of late stent thrombosis and further modifications of drug-eluting stents will hopefully focus on that. The overall safety of drug-eluting stents is pretty good and in terms of relative risk improvement in terms of the safety it is going to be hard to improve because you can get a small relative risk improvement but absolute risk is hard to improve upon because rates of adverse safety endpoints are relatively low. These stents are not perfect， they are a lot better than