Abbott Heart
Stent Better at Keeping Coronary Arteries Open and Reducing
Adverse Events
XIENCE Stent --
Part of a New Generation of "DES 2.0"
|
|
May 13, 2008 -- Two-year
outcomes from the
SPIRIT III trial,
studying the XIENCE™ V
Everolimus Eluting Coronary Stent System, were presented today
at the EuroPCR 2008 meeting in Barcelona -- and the results showed
Abbott's second generation stent to be superior to Boston
Scientific's market-leading TAXUS paclitaxel-eluting stent in
several important criteria.
- Major Adverse Cardiac Events
(MACE) -- a 45% reduction for XIENCE V compared to TAXUS
(7.3% vs. 12.8%, p-value=0.004)*. MACE is an important composite
clinical measure of safety and efficacy outcomes for patients,
defined as
cardiac death, heart attack (MI), or ischemia-driven target lesion
revascularization;
- Target Vessel Failure (TVF) -- a
32% reduction in the risk of cardiac
events
related
to
the treated vessel compared
to TAXUS
(10.7% vs. 15.4%, p-value=0.04)*. TVF is a composite clinical
measure of safety and efficacy outcomes
defined as cardiac death, heart attack or target vessel revascularization
(TVR);
- Target Lesion Revascularization (TLR) --
a 40% percent reduction in the risk of ischemia-driven target lesion
revascularization
as compared to TAXUS (4.6% vs. 7.5%,
p-value=0.07)*;
- Very Late Stent Thrombosis --
stent thrombosis, occurring between one and two years, as per
the Academic Research Consortium (ARC) definition of definite/probable
stent
thrombosis was 0.3% XIENCE V and 1.0% for TAXUS; using the
the SPIRIT III protocol definition (which pre-dated ARC) the
rate was 0.2% vs. 1.0%.
The SPIRIT III two-year results were presented
by Gregg W. Stone, M.D., principal investigator of the SPIRIT III
trial, during the
late-breaking clinical trials session at EuroPCR 2008. Dr. Stone has
a unique perspective on the XIENCE vs. TAXUS comparison, since
he was also the principal investigator for the first generation
TAXUS stent
which
was approved
by the FDA four years
ago.
Gregg W.
Stone, MD |
|
When the one-year results
for the SPIRIT III XIENCE trial were published three weeks
ago
in JAMA, Dr. Stone commented:
"This
large-scale, prospective, randomized, single-blind, controlled
study demonstrates that
an everolimus-eluting stent, compared with a widely used paclitaxel-eluting
stent, results in a significant reduction in angiographic in-segment
late loss at 8 months, with non-inferior 9-month rates of ischemia-driven
target vessel failure. Thus, the 2 prespecified FDA regulatory
requirements required for the trial to be considered successful
were met.
"The reduction in late loss was confirmed by the findings
from intravascular ultrasound, which demonstrated an approximate
50% reduction in volumetric neointimal hyperplasia."
|
Today Dr. Stone added: "Not only did XIENCE
V clearly differentiate itself from the TAXUS stent in the first
year after
treatment, it has now demonstrated even more positive effects at
two years in the SPIRIT III trial. As measured by clinically significant
reductions in target vessel failure and MACE, XIENCE V demonstrated
an even greater
improvement in patient outcomes compared to TAXUS at two years
than at one year, driven by numerically lower rates of heart attacks
and lower observed rates of re-intervention of the target lesion.
We also saw encouraging trends for lower observed rates of late
and very late stent thrombosis in XIENCE V-treated patients, especially
in those who discontinued dual antiplatelet therapy."
Utilizing a different drug, a more flexible
stent with thinner struts and a thinner polymeric-coating, Abbott's
XIENCE
stent represents another major potential addition to the interventional
cardiologist's armamentarium -- a package of second generation
devices, drugs, diagnostics and techniques which Angioplasty.Org
has dubbed, "DES
2.0".
The XIENCE™ V everolimus-eluting stent, available
since October 2006 in Europe, has not yet been approved
for use in the United States, although the FDA's own Circulatory
System Devices Advisory Panel recommended approval five months ago.
Publication
of the SPIRIT III trial findings in JAMA and the longer-term safety
results, shown in today's presentation, may move that approval forward,
although the FDA is certain
to require
long-term
follow-up of a large patient cohort as part of the approval, much
as it did for Medtronic's Endeavor stent, approved
in February 2008.
Anatomy of the XIENCE V Stent
As
described in Angioplasty.Org's Drug-Eluting
Stent Overview, there
are three major components to a drug-eluting stent (DES):
- The
type of metal stent that carries the drug coating;
- The stent coating (polymeric or other) which contains the
drug and delivers it to the arterial wall;
- The drug itself -- how it acts in the body to prevent restenosis.
Improvements in each of these components may be one reason
that the XIENCE has outperformed the first generation TAXUS.
|
|
Artist Rendition
of XIENCE V Coronary Stent (an investigational
device in the United States) |
The bare-metal foundation stent of the XIENCE system
is the Multi-Link Vision stent,
originally developed by Guidant (before the company was split up
and acquired by Abbott and Boston Scientific). The Multi-Link was
one of the most
popular bare metal stents and was made not of stainless steel, like
first generation stents, but of a cobalt-chromium
alloy -- allowing greater strength with thinner metal struts -- 40%
thinner than the TAXUS struts (89
vs 148 µm). Thinner metal surfaces may translate to a lower
tendency for cell growth which can reblock a stent; thinner struts can make
the stent more flexible or "deliverable" as
well.
Like the TAXUS, the polymer
(plastic) coating of the XIENCE is a permanent durable coating
(biocompatible, but
not biodegradable). However, the coating is much thinner, less
than half the thickness of the TAXUS (7.8 µm
vs 16.0 µm). What effect this may have is not proven, but some
cardiologists feel that a thinner polymer allows the stent to be more
easily expanded. Additionally, Angioplasty.Org has been working
with cardiologists at the University of Texas, San Antonio, who believe
that the polymers of first generation DES may be associated with
long-term
hypersensitivity reactions. Whether a thinner or different polymer
will have any effect is yet to be seen.
Finally, the drug itself -- everolimus is a derivative
of rapamycin (sirolimus) which is used in the CYPHER
stent. However, in preclinical studies, everolimus-eluting stents
are reported to have shown more
rapid
endothelialization
(covering
of the stent by the body's endothelial cells) than either paclitaxel
or sirolimus-based devices. Delayed endothelialization has been posited
as one of the causes of increased late stent thrombosis in DES. Although
at one year, there was no measured difference in
late stent thrombosis
between the XIENCE and TAXUS stents, during the period between
one and two years, the TAXUS cohort experienced three times the stent
thrombosis.
DES 2.0
Devices -- The interventional cardiology community is clearly looking
forward to this new generation of devices. Already the sales of drug-eluting
stents are beginning to pick up, having dropped from 90% penetration
down to the low 60% ranges, due to the fears about stent thrombosis.
But the new devices are only a part of the story.
Drugs -- Many lessons have now been learned about
the required and concomitant antiplatelet therapy. Originally prescribed
for six
months, that regimen has now been extended to a year or more. Cardiologists
and related medical personnel are also much more aware of the dangers
of premature cessation and protocols are being developed for those
patients who are in need of surgery and must stop.
Additionally, a very
recent study has identified a possible "rebound" effect with clopidogrel
(Plavix) -- a spiking of increased platelet activation right after
stopping -- something that carries double the risk of heart
attack, something that may turn out to be of much greater concern
than the stent
thrombosis issue. If a safer method for stopping Plavix, such as
a tapering off of the dosage, can be found, the benefits for patients
will be extensive.
Diagnostics -- A final component of "DES
2.0", as Angioplasty.Org defines it, is the much more advanced process
of diagnosing coronary artery disease, of determining whether or
not a blockage needs intervention or can be treated with medical
therapy and lifestyle changes, of deciding on the best strategy for
revascularization, if the blockage does need an intervention. The
new imaging technologies of multislice or multidetector CT angiography,
CT perfusion imaging, intravascular ultrasound (IVUS), the futuristic
Optical Coherence Tomography (OCT),
cardiac Magnetic Resonance, as well as new types of functional measurement
such as FFR -- all these recent technologies are creating a new paradigm
for the way cardiologists look at the coronary circulation and the
patient.
The "dawning" of this new age differs
considerably from the rushed enthusiasm of the first generation of
drug-eluting
stents, where many believed that the two decade-old battle against
restenosis had finally been won. The "DES 2.0" world is
more cautious, more complex, yet more precise and ultimately will
push the treatment
of heart disease forward, benefiting tens of thousands of patients.
In
the same issue of JAMA as the XIENCE one-year results,
angioplasty pioneer
Dr. David
Holmes
of
the Mayo
Clinic
and Dr. Manesh R. Patel of Duke used these words to conclude their
editorial, "Next-Generation
DES: A Spirited
Step Forward or More of the Same?":
"These outcomes measured over time will
provide both efficacy and safety measures for currently available
and future
interventional devices. Patients will not distinguish between
target lesion and target vessel failure, even if clinicians
do not think
the device is plausibly related. Indeed, these are the outcomes
that practicing interventional cardiologists must demand prior
to widespread
use of a new device. Physicians must continue to be judicious
stewards of the interventional toolbox so that patients continue
to allow
them the privilege of performing procedures intended to improve
their health."
reported by Burt Cohen, Angioplasty,Org, May 13, 2008
|