Transcript Coaated stents: a new era

Coated stents: a new era
Ulrich Sigwart MD
Director, Cardiovascular Institute
Royal Brompton Hospital
London, United Kingdom
Cindy Grines MD
Director, Cardiac Catheterization Laboratory
William Beaumont Hospital
Royal Oak, Michigan, USA
Patrick Serruys MD
Director, Interventional Cardiology Laboratory
Thoraxcenter
Rotterdam, The Netherlands
Spencer King III MD
Clinical Professor of Medicine
Emory University School of Medicine
Atlanta, 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
Coated stents
Could there be more late thrombosis
with drug-coated stents?
“There is some evidence that
we can run into trouble with
these drug-eluting stents.”
Serruys
©2001
Conceptis Technologies
Animal data suggest toxic levels with
implications for the endothelium around doses
of 70 g actinomycin
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
IVUS results
Malapposition
Group
Control
Treated
4%
20%
We are talking about IVUS at late follow-up
Some incomplete apposition has been
shown
We cannot expect positive remodeling
Serruys
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 sirolimuscoated 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
Coated stents
How long does the FDA intend
to 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 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
Coated stents
Could other coatings be effective?
ASPECT: 4% restenosis with paclitaxelcoated 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-month
QCA results
Stent
High-dose Low-dose
Bare
p value
Mean luminal
diameter (mm)
2.530.72 2.280.83 1.790.86 <0.001
Late loss (mm)
0.290.72 0.570.71 1.040.83 <0.001
Mean diameter
stenosis
Binary restenosis
1421%
2325%
3927%
<0.001
4%
12%
27%
<0.001
Park S-J et al. TCT 2001
Coated stents
Is the clinical importance
of 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 brachytherapytreated 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 of
a new era, everything
is probably overpriced.”
Competition will most
likely 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
Bx-stent platform
Source: Cordis
Despite all problems, the
enthusiasm about this technique
is probably justified
The SIRIUS trial will show its
effectiveness for more complex
lesions
King
Coated stents
Angiographic results
Angiographic results with sirolimus-eluting stent
post
pre
4 months
Source: Cordis
1 year