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Stent News from the
ACC.10: Monday
New Studies Presented
at American College of Cardiology 59th Annual Scientific Sessions:
SORT-OUT III (Cypher vs. Endeavor)
Taxus PERSEUS (Element vs.
Express)
ISAR-TEST-2 (Polymer-Free Dual Drug-Eluting Stent)
Abbott's ABSORB Bioabsorbable Stent Program -- Phase Two
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A Sea of
Poster Presentations |
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March 15, 2010 --
All four U.S. stent manufacturers were represented in various
studies
presented at today's 59th Annual Scientific Sessions of the American
College of Cardiology in Atlanta, GA, an event attended by an
estimated 16,000 cardiology professionals. The studies revealed
data about old vs. new devices, and the results ranged
from unsurprising to controversial to unparalleled.
First, the controversial....
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SORT-OUT III 18-month Data: Cypher
vs. Endeavor
When
the 9-month data of this trial were presented at TCT 2008, the results were disappointing
for Medtronic's new Endeavor zotarolimus-eluting stent -- there were
more major adverse events and a higher stent thrombosis rate than
with the older first generation sirolimus-eluting Cypher. The study,
conducted in Denmark, came under some criticism, but many were surprised
by the data, especially since the Endeavor had shown
a superior safety profile: one of its main advantages.
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time, Dr. David Kandzari, lead investigator for several of
the Medtronic-sponsored Endeavor trials, opined to theheart.org that
these data "'throw a wrench in the mechanics of the ENDEAVOR
program,' because the findings are not in line with earlier
tests of the zotarolimus-eluting stent." In fact, these
findings have not been in line with most trials
involving the
Cypher
stent, leading Dr. Kandzari to tell Angioplasty.Org that, "It's
not that...Endeavor performed unusually poorly; it's that Cypher
actually did very well," better than in any other trial. And
Dr. Kandzari is very familiar with the Cypher stent, having served
as Chief Medical Officer for Cordis (maker of the Cypher) from 2006-2008. |
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Dr. David
E. Kandzari |
So today the 18-month data were presented (and
simultaneously published in The
Lancet) and they showed no change: Cypher still bested
Endeavor on all fronts, although
both
stents
showed very good results. Medtronic, a co-sponsor of the trial, was,
of course, not pleased with these results and issued a
strong statement criticizing the "unconventional
methodology" of
SORT-OUT III and a laundry list of complaints. Some of their key
points included the fact that patient records from a government database
were used instead of the traditional one-on-one patient
follow-up, and that nearly 60% (over 3,300) of eligible patients
were excluded (the study authors' odd statement about this was only
that "...the
all-comer principle was not used by all investigators, so some eligible
patients
were
not
randomly
assigned
to treatment". Another "anomaly" was that periprocedural
MIs were excluded as an adverse event. These are small "heart
attacks" that
can occur during the angioplasty and several studies have linked
periprocedural MIs with late mortality. Since the Endeavor
stent has consistently
shown much lower rates of periprocedural MIs than Cypher or Taxus,
Medtronic claims that this skewed the data against
Endeavor.
The Medtronic critique continued by quoting statistics
from a number of other independent studies conducted
over the years, showing consistently higher event rates
for the Cypher than those shown in SORT-OUT III. In fact, as Angioplasty.Org
reported yesterday regarding the ENDEAVOR
III 5-Year Results, while the Cypher stent initially
showed lower adverse events, at two years Cypher crossed
over and by five years these events were 60% higher than
the Endeavor. This two year cross-over, or late "catch-up" phenomenon
with the Cypher,
has been seen in other trials as well, most notably, the SIRTAX-LATE.
Medtronic's
detailed critique can be read in full here ("Medtronic
Responds to SORT-OUT III Stent Study"). Perhaps
at the next reporting of SORT-OUT III, the late "catch-up" will alter
the bottom line. However, it is possible that these questions of
Cypher vs. Endeavor may finally be
resolved by the very
large 8,800
patient PROTECT study currently in process, although
the results will not be available for two years down the line.
Taxus PERSEUS
(Element vs. Express)
Although Boston Scientific has been doing very well selling its version
of Abbott's Xience everolimus-eluting stent, called Promus, its agreement
with Abbott runs out in 2012, so the company has been putting together
the
various
components of a brand-new stent. One of these is the stent platform.
Taxus Express, its first generation DES, was built on a stent with
relatively thick struts and with a polymer that some clinicians found
"sticky". The newly-designed Element stent is made of a platinum
chromium alloy, with thinner and stronger struts, making the stent
more deliverable
and durable. The Taxus Element is this stent platform coated with the
current Taxus paclitaxel-eluting polymer, but Boston is currently selling
its Promus Element in Europe, coated with everolimus like the Promus/Xience,
and is hoping that the FDA will approve it in the next 18 months or
so.
The Taxus PERSEUS study presented today showed
similar safety and efficacy between the older Taxus Express and the
newer platform Taxus Element. Even though Reuters headlined this
story, "Boston
Scientific's new stent good as the old one", the company
is hoping for approval of the Taxus Element in 2011 and then a move
towards Boston's ultimate goal
of gaining approval for
its
everolimus-eluting
Promus
Element, giving it two new stents with two different-acting drugs
on a newly designed second generation platform. More details about
the PERSEUS study can be found in the company's press release, "PERSEUS
Trial Results Demonstrate Positive Safety and Efficacy Outcomes for
Boston Scientific's Novel Platinum Chromium TAXUS® Element™ Stent
System".
ISAR-TEST-2 (Polymer-Free Dual Drug-Eluting Stent)
Drug-eluting stents are coated with polymers which allow the drug
of choice to "elute" over weeks or months to keep excess
tissue growth in check. But some polymers have been called into
question
as possibly causing a hypersensitivity reaction over time -- one
that may cause late stent malapposition, where the arterial wall
almost
aneurysmally expands away from the stent, resulting in an opening
or "pocket" which can be the nexus for a thrombus --
thus late stent thrombosis. The Endeavor stent uses a biocompatible
polymer
that seems to avoid this problem. Another solution is to eliminate
the polymer altogether. That's what the cardiologists at Deutsches
Herzzentrum of Munich, Germany did and additionally they added
two different drugs: sirolimus (used on the Cypher stent) and probucol,
an antihyperlipidemic drug. ISAR-TEST-2 compared this novel polymer-free
stent with both the Endeavor and the Cypher in a total of 1,007
patients. The results were presented today by presented by Dr Robert
Byrne: after
two
years
the dual DES and Endeavor stent maintained their antiproliferative
properties, with little change between one and two years, while
the Cypher stent had
significantly more TLR and restenosis -- the existence of this
late "catch-up" phenomenon with the Cypher was most
interesting, given
the controversy
earlier in the day about
the
SORT-OUT
III study. The one to two year rates of TLR were: 6.8% to 7.7%
for the Dual DES (change of 0.9%); 13.6% to 14.3% for the Endeavor
(change of 0.7%); and 7.2% to 10.7% for the Cypher (change of 3.5%).
Although the initial TLR of the Endeavor was greater, the dual
DES and Endeavor both proved to be consistent, with little change,
through year two.
ABSORB Bioabsorbable Stent -- Phase Two
Abbott's initial foray into the bioabsorbable or biodegradable stent
concept was a small feasibility trial of just 30 patients. The
company's phase two trial presented today by lead investigator
Prof. Patrick
Serruys of Rotterdam showed results from 101 patients at 30 days
and the results were very favorable: no cases of stent thrombosis,
no need for repeat procedures (TLR) and a MACE rate of 2%. Follow
up of these patients will be presented at future meetings, but
the
potential for a device that does the work it is supposed to do
and then disappears is great. Not having permanent metal implants
in the coronary arteries avoids any vasomotor restrictions that
can sometimes occur, and also might make future bypass
surgeries or catheter-based revascularizations more successful
since the artery would return to an almost pre-intervention state.
One interesting point made by Dr. David Kandzari
to Angioplasty.Org has to do with future randomized clinical trials,
testing such a stent against the current crop of DES. Because the
safety profile of second generation DES is already so good, he stated:
"...to design a trial to demonstrate superior
safety...your trial size would be astronomically high to prove the
benefit of statistical
significance. And you may not achieve
that goal.
I think that most newer drug-eluting stents with bioresorbable
polymers or bioresorbable stents will be adopted more on intuition
and clinical
perception rather than on actual demonstration of superiority compared
with some of the existing DES we have today."
Reported by Burt Cohen, March 15, 2010
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