Questions and Answers (May 14, 2002)

May 14, 2002 William O’Neill: There is a question for Dean Kereiakes. How will decreasing or eliminating restenosis impact surgical volume — obviously a major concern for surgeons and hospitals because coronary bypass surgery is a very profitable service line? What do you predict will happen to the surgery volume in Christ Hospital once either vascular brachytherapy or drug-eluting stents become more widely used? Dean Kereiakes: We make frequent use of vascular brachytherapy at Christ Hospital and our clinical TVR rate is close to what Greg presented. It is nice to see in real life, high-volume community hospital practice that we are able to achieve such low clinical TVR rates for drug-eluting stents.We have modeled the cost data out for three years and have assumed a 10% annual reduction in surgical volume. We have not yet determined how much of that volume will be attributable to restenosis business versus the diversion of cases that would have been referred to surgery. I showed the one-year data, but we have data for three years that assume incremental reimbursement at different time frames from both Medicare and private payors. I think a safe model is probably a 10% annual decrease in surgical volumes. William O’Neill: Those are some interesting assumptions. I spoke with one European site that was able to obtain a budget for coated stents by cutting surgical budgets 30%. There are ways to address this, but essentially, money will be going from one bucket to another. A $3 million cardiology budget increase will not just magically appear. Something will have to give in the budget — other reimbursements will decrease, programs will be cut, and so forth. I have a question for Greg Braden concerning Plavix. Would you comment on subacute thrombosis and the cost of using Plavix? Greg Braden: In most pharmacies, Plavix use will run close to $100 a month. The need for Plavix after that is going to be pretty well established for at least three months, especially in light of the data that was released. I think an increasing number of patients will be treated with Plavix. It is a type of chronic therapy anyway. That expense may not just be a unique experience related to vascular brachytherapy. It is an expensive drug and it would be nice if it were not so costly. Global cost-wise, it is probably an inexpensive drug, but it does pose problems for some individual patients. There is not third-party reimbursement with that. William O’Neill: Steve, there is a question about the use of drug-eluting stents and whether glycoprotein receptor therapy costs will change or decrease. Can you comment briefly on the trials you are conducting and how you will use glycoprotein receptor blockers with drug-eluting stents? Stephen Ramee: Our current practice is to use IIb/IIIa inhibitors in coronary interventions for roughly 20% of the cases which tend to be the acute unstable angina patients who are not preloaded with Plavix. We probably do things a little differently than most centers in the United States anyway, because we are not treating all of our patients with IIb/IIIa inhibitors. Drug-eluting stents will probably not alter that. Drug-eluting stents, like vascular brachytherapy, will probably mandate longer treatment with oral anti-platelet therapy, with a 3–6 month course as the likely treatment length. William O’Neill: Dean, at your hospital, I think you are at the true end of the spectrum. You have been a little more aggressive in using glycoprotein receptor blockers. Do you foresee that changing with this incremental cost of drug-eluting stents? Dean Kereiakes: We have prepared ourselves for that, Bill. We just had a paper accepted this week in the American Journal of Cardiology that analyzes the EPIC, EPILOG, and EPISTENT trials. We analyzed the clinical predictors of a survival advantage in favor of abciximab versus placebo for the 6,000 patients involved in these trials. As you may know, clinical variables have never been good at predicting the response to GP IIb/IIIa blockade with respect to reduction in triple endpoint events at 30 days (death, myocardial infarction, and urgent revascularization). You remember the original EPILOG paper published in 1997 (New England Journal of Medicine) which showed that high-risk patients had a very similar reduction in triple endpoint events as did low-risk patients at 30 days following enrollment. However, by using nine clinical variables, each of which was demonstrated by multivariate analysis to be associated with increased mortality to three-years follow-up, we were able to predict more accurately which patients will have a survival advantage following abciximab therapy. Those in the high tertile of risk actually had a 2.7% decrease in three-year mortality following abciximab therapy, whereas those in the lowest tertile of risk had no detectable reduction in mortality. Rather than arbitrarily and empirically rationing down the use of abciximab, we would like to use an algorithm to appropriately select patients who are likely to benefit most from this therapy. William O’Neill: That will sort of outweigh some of these? Dean Kereiakes: At least one-third — perhaps more — of the utilization of abciximab will be reduced. However, use of abciximab should still remain between 33 and 66% of cases. William O’Neill: Here is a good question that came in for the panel and which Dean alluded to briefly. In March 2003, the Cypher stents will be available for sale in Cincinnati. Do you plan to stock them, and if so, are you going to limit their use? Dean Kereiakes: Ron Waksman and I had this discussion recently at the Washington Hospital Center which held the annual meeting for the JP Morgan analysts. We are both using drug-eluting stents in clinical trials. In fact, we have five different drug-eluting stents that we have either used or will be testing at the Christ Hospital through the Lindner Research Center. Both Ron and I said that we favor not putting the drug-eluting stent on the shelf in the absence of adequate reimbursement. William O’Neill: The idea is that there may be decent short-term results and you won’t have a competitive disadvantage. Dean Kereiakes: Yes, that’s what we both believe. Campbell Rogers attended that meeting as well and felt that in Boston the competitive disadvantage might be greater. They appear to be more intimidated by it and may be more likely to offer drug-eluting stents without reimbursement. Frankly, if you lose $1 million a month in the absence of any reimbursement, you might not have a shelf to put the stents on. If you analyze your data at Beaumont Hospital, Bill, and you place more stents than we do, and you will lose at least $7 million by year-one, probably more. William O’Neill: You’re exactly right about that. Greg, in March 2003, what are you going to do — at least as of today — in terms of the availability or rationing of drug-eluting stents? Greg Braden: We will probably place these stents early on. I don’t foresee a wholesale switchover to drug-eluting stents at our institution once they become available. They will probably end up being used for high-risk applications for which they really have not yet been tested for. However, I think in this class-conscious world, we forget that restenosis is a relatively benign process and we actually have a good treatment for it. Also, I think judicious placement of them in higher-risk cases is probably the most cost-effective way to use them. We should use them early if there is not widespread reimbursement. If these stents are reimbursed, then we could talk about the overall health economic benefit of drug-coated stents for everyone. Clearly, when you have clinical restenosis rates of less than 10% and larger vessels with shorter stents, I am not certain that we need a drug-coated stent in those scenarios. If patients do return, we have a very effective treatment for those who are not going to die from in-stent restenosis. Dean Kereiakes: I would like to comment on that. I appreciate Greg’s point, but I would like to offer the following: If one truly applies evidence-based medicine, you will not treat those “high-risk” cases that Greg just mentioned. Instead, you will treat the same types of cases that were studied in the clinical trials that proved efficacy for this technology. That does not include multi-vessel disease, vein grafts, etc., and applies largely to single vessel, single lesion disease. William O’Neill: That’s exactly what our approach will be. We will apply strict scientific evidence-based medicine and will treat the lesions that are RAVEL-like or SIRIUS-like or DELIVER-like for which the therapy has been proven. However, there is really no good safety and efficacy data for procedures using a full-metal jacket on a right coronary of the ostium using t-PA. Let’s not forget the efficacy and safety data that you have gathered on > 40 mm length applications of drug-eluting stents. What happens downstream to the drug and the artery is still unknown in terms of what is appropriate to use. We will probably ration use of the stents, but in an ethical fashion. Stephen Ramee: At Ochsner, we will probably use these stents more for single-vessel single-stent applications rather than for multi-vessel applications — that’s one thing you did not mention. We have a lot of patients who have multi-vessel interventions and as you know, the more stents you place, the higher the cost will be. Those are the patients whom we will triage to bare-metal stents plus vascular brachytherapy for restenosis. William O’Neill: This has been a wonderfully informative discussion and I want to thank all of you for your participation. I also want to thank Novoste for sponsoring this meeting.