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Coated stents: a new eraUlrich Sigwart MD
Director, Cardiovascular InstituteRoyal Brompton HospitalLondon, United Kingdom
Cindy Grines MDDirector, Cardiac Catheterization LaboratoryWilliam Beaumont HospitalRoyal Oak, Michigan, USA
Patrick Serruys MDDirector, Interventional Cardiology LaboratoryThoraxcenterRotterdam, The Netherlands
Spencer King III MDClinical Professor of MedicineEmory University School of MedicineAtlanta, Georgia, USA
Coated stents A hot topic
Local drug delivery using stents is a hot topic
Morice M-C, et al. ESC 2001
Issues to be discussed
• thrombosis
• rapid initial endothelialization
• side effects
“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?
©2001Conceptis Technologies
Coated stents
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
Coated stents
Malapposition in RAVEL
We are talking about IVUS at late follow-up
Some incomplete apposition has been shown
We cannot expect positive remodelingSerruys
Group
IVUS results Control Treated
Malapposition 4% 20%
Coated stents
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
Coated stents
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
Coated stents
Questions remain
Is the coating protected once you have an endothelium on the cell?
Could another wave of proliferation be initiated once the drug has been “eaten up” from the stent surface?
Coated stents
Porcine models
Studies in pigs show reduction of in-stent neointimal hyperplasia with sirolimus-coated stents
Suzuki T, et al. Circulation2001;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 impressiveSerruys
Coated stents
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
Coated stents
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
Coated stents
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
Coated stents
Heparin
A recent trial did not show any difference between a heparin-coated Jostent and an uncoated Jostent
Wöhrle J, et al. Eur Heart J2001;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
Coated stents
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
Coated stents
ASPECT results
6-monthQCA results
Stent
High-dose Low-dose Bare p value
Mean luminal diameter (mm)
2.530.72 2.280.83
1.790.86
<0.001
Late loss (mm) 0.290.72 0.570.71
1.040.83
<0.001
Mean diameter stenosis
1421% 2325% 3927% <0.001
Binary restenosis 4% 12% 27% <0.001
Park S-J et al. TCT 2001
Coated stents
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
Coated stents
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
Coated stents
Treatment options
Several treatment options
•anti-inflammatory drugs
•antiproliferatives
•drugs blocking the extracellular matrix
Coated stents
The future
“It’s the beginning of an era. I think there will be a very long battle to find a good compound.”
Serruys
“[This is] the first glance of what the future will bring. There will be lots of work to be done.”
Sigwart
Coated stents
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
Coated stents
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
Coated stents
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
Coated stents
Stent pricing
“In the beginning ofa new era, everythingis probably overpriced.”
Competition will mostlikely lower the price
Sigwart
Coated stents
Potential problems
People might too easily put a powerful drug on a stent Serruys
There is always the danger of creating a new disease
Sigwart
Despite all problems, the enthusiasm about this technique is probably justified
The SIRIUS trial will show its effectiveness for more complex lesions
King
Bx-stent platformSource: Cordis
Coated stents