Coated stents: a new era

1. Coated stents: a new era

2. A hot topic

3. �There is some evidence that we can run into trouble with these drug-eluting stents.�  Serruys Animal data suggest toxic levels with implications for the endothelium around doses of 70 ?g actinomycin Could there be more late thrombosiswith drug-coated stents?

4. Occlusions RAVEL no subacute occlusions despite 2 months of clopidogrel treatment Liistro and Colombo 1 case of late occlusion with paclitaxel-eluting stent  Liistro F, Colombo A.  Heart 2001;86(3):262-264 ASPECT subacute occlusion with cilostazol and aspirin �We have to read case by case.�  Serruys

5. Malapposition in RAVEL We are talking about IVUS at late follow-up Some incomplete apposition has been shown We cannot expect positive remodeling Serruys

6. Remodeling hypotheses Any thrombotic material in an unstable patient will not be colonized by smooth muscle cells migrating in the direction of the lumen Positive remodeling might occur, detaching the wall from the stent �It�s clear that it�s a very powerful biomechanical technology.� Serruys

7. Self-expanding stents Self-expanding stents go with the development of the artery Sigwart Artery walls could become thinner if tissue behind the stent regresses There is the possibility of late aneurysm with self-expanding stents �I�d be a little concerned.� Grines

8. Questions remain

9. Porcine models Studies in pigs show reduction of in-stent neointimal hyperplasia with sirolimus-coated stents Suzuki T, et al. Circulation 2001;104(10):1188-1193 There might be discrepancies between what the porcine model is showing and what is happening in humans 18-month follow-up looks very impressive Serruys

10. How long does the FDA intendto follow these patients? Brachytherapy was approved despite incidents of late thrombosis; the benefit outweighed the potential downside �There�s no way that you can follow up patients as long as there are questions.� King

11. Does the FDA require a 5-year follow-up? The FDA does not wait 5 years for approval, but is interested in postmarket surveillance King Analysts on Wall Street have estimated the incremental value of the drug-coated stent in 2005 to be $4 billion �If the FDA then unravels the problem again and�says �we missed some very important aspect in the long-term follow-up,� that would be a catastrophe, wouldn�t it?� Sigwart

12. RAVEL trial design 15/26 control patients had clinically driven target-lesion revascularizations �Probably 1/3 of the patients were treated for oculo-stenotic reflex.� Oculo-stenotic reflex prevented either with stringent intervention criteria or by double randomization, with an angiographic arm and a clinical arm  Serruys

13. Heparin A recent trial did not show any difference between a heparin-coated Jostent and an uncoated Jostent  W�hrle J, et al. Eur Heart J 2001;22(19):1808-1816 Should we forget about the focus on antithrombotic mechanisms? heparin in animal studies required high doses to reduce the proliferative response heparin on the stent was at a lower dose and was not eluted into the surrounding tissues Grines

14. Could other coatings be effective? ASPECT: 4% restenosis with paclitaxel-coated stent Park S-J, et al. TCT 2001 Inclusion criteria differed from RAVEL diabetics included longer lesion lengths �It�s probably going to end up being comparable to the RAVEL results.�  Grines

15. ASPECT results

16. Is the clinical importanceof therapies overestimated? A therapy reducing the late loss index by 100% might be equally effective as one reducing it by 50% in terms of clinical outcomes �When we have a very powerful agent�that can really block the proliferation, when we examine it with things like IVUS, it exaggerates the benefit.�  King

17. Softer coating Would you rather coat your stent with softer medication that has an anticipated 5% restenosis rate than with a harder but more effective material? �I would.�  Grines �Yes, I think that all of us have felt that, if you ever got down really into single digits with interventions� there would not be an inhibition to doing it anymore.�  King

18. Treatment options Several treatment options anti-inflammatory drugs antiproliferatives drugs blocking the extracellular matrix

19. The future

20. Stent pricing Stents will be priced at about $3000, similar to the cost of brachytherapy Stents are user-friendly and are going to be much more widely adapted �We are going to have a lot of pressure from our patients to use a stent like this. Virtually every day a patient brings up a drug-coated stent to me.� Grines

21. Stent pricing Cost of coated stents is a critical issue Because of the high cost of stents only highly culprit lesions are treated With 0% restenosis there will be increasing interest in �plaque sealing� �The cost could be quite exorbitant. It�s an important issue but I don�t think it ought to get in the way of the science and the therapy becoming available.�  King

22. Stent pricing Higher cost of eluting stents would be offset by the savings related to fewer cutting balloon and brachytherapy-treated patients returning with restenosis Stent costs should not exceed $1000 in Europe because beyond this, surgery could be more cost-effective �If the cost is too high, society will lose the benefit of having created something that is less invasive.�  Serruys

23. Stent pricing �In the beginning ofa new era, everythingis probably overpriced.� Competition will mostlikely lower the price Sigwart

24. Potential problems

25. Angiographic results