December
28,
2006 -- 10:30pm ET
DES'ed and Confused: What the FDA Stent Safety
Panel Means for Patients
If you had been worrying about that drug-eluting
stent (DES) implanted in your coronary artery, your concerns were
no doubt greatly reduced by the extensive news coverage following
the much-anticipated FDA stent safety panel held on December 7-8. Here's
a small sample:
Drug-Coated
Stents Don't Boost Death Risk, U.S. Advisers Say (HealthDay)
Panel says wide use of drug-coated stents risky (Reuters)
Panel:
Drug-Coated Stents Are Safe (CBS / AP)
Panel
Urges Caution on Coated Stents (New York Times)
Drug-Eluting
Stents Do Not Increase Risk of Heart Attack or Death, Benefits Outweigh
Increased Blood Clot Risk, FDA Advisory Panel States (Kaiser Network)
FDA
Advisory Panel Recommends More Warnings About Drug-Eluting Stents (Kaiser
Network - 3 days later)
Confused? Of course you are. And if you are the
recipient of a drug-eluting stent, you're probably confused
and scared -- because the stakes are high, and this device
can't
be taken out!
So, let's take a breath of fresh air: inhale...and now
slowly exhale.
The clinical trials for both the
Taxus (Boston Scientific) and the Cypher (Cordis / Johnson & Johnson)
drug-eluting stents were done in simple uncomplicated patients:
those with a previously untreated ("de
novo") blockage in a single vessel in a straight-forward location.
The stents were approved by the FDA for those situations, because they
showed a clear and significant benefit over bare metal stents: much
lower chance of reblockage.
In order to get their devices
approved, companies tend to design their clinical trials for this
straight-forward type of patient
population
(one that will show a clear benefit). But in the "real world", almost
two-thirds of the time, interventional cardiologists use these devices
outside
of these strict and limiting definitions. There
is nothing illegal about this.
Physicians have
studied these additional uses and shared this data with other doctors
at the major heart meetings. They use these devices in many "off-label"
indications (multiple stents, multiple vessels, in-stent restenosis)
because they feel that the patient is better served by the newer
device that shows less restenosis. More restenosis means more repeat
procedures and more complications; studies have shown that restenosis
is not benign -- it increases the incidence of heart attack and hospitalization.
Furthermore, prior to drug-eluting stents, physicians often used
bare metal stents in these same off-label indications -- they did
not perform as well as drug-eluting stents do.
But over the past year, concerns about the tendency of
drug-eluting stent patients to experience stent thrombosis (not
a reblockage, per se, but an acute gathering of platelets, a.k.a.
a blood clot) six months or more after implantation has prompted
a new look at the use of these devices. The incidence seems very
small, but the data about this population, as evidenced at the FDA
hearing, are incomplete, not very robust, in the words of one panelist
to
me, "We've got lots
of data -- it's
just that it's lousy data!"
The FDA panel clearly stated that, when used within
the confines of the approved uses of the original clinical trial population,
there is no increased risk with drug-eluting stents -- and there
is a considerable benefit: freedom from restenosis.
But the data for "off-label" uses is not clear:
these are more complex blockages, in sicker patients, with more Plavix
and aspirin -- in the words of panelist Dr. Eric Topol, there are "a
lot of moving parts -- it's a big grey area, and the risk may be
considerable".
And there lies the problem with "off-label" use
-- it's not that this use is dangerous; it's that the FDA doesn't
regulate
"off-label" use and therefore doesn't require long-term studies
of patients in these situations before approval. So the data is not
so clear. The FDA did require Cordis to do a followup post-market
study after approval of the Cypher
stent in 2003. But Cordis stopped collecting data after one year,
and they were taken to task by the panel chairman
Dr. William Maisel for not following up longer. However, the
FDA agreed with Cordis that they only requested a one-year
follow-up -- and added that in retrospect, it should have been longer,
and probably will be for future devices.
As to how this affects patients, we wrote a "Patient
Advisory" right after the European Congress of Cardiology four
months ago, and nothing discussed at the FDA panel has changed what's
in that Advisory. Most cardiologists have been recommending longer-term
Plavix and aspirin for quite a while now. I suggest patients with
questions read that Advisory and discuss it with your doctor.
For many patients drug-eluting stents work great; for some not necessarily,
especially those who
have a
risk of bleeding, making long-term Plavix therapy not a good option.
What has changed this month is something I discussed
in my
last entry: two days of panel discussions by the FDA have given
these problems a public airing, providing instant and
widespread "patient education". The message was that there
is something to be concerned about after all.
And this message prompted an all-out defense by the
two drug-eluting stent manufacturers: Boston Scientific immediately
ran full-page ads in all the
major U.S. newspapers, Cordis issued press releases about "educational
programs", and both manufacturers mass-emailed the professional
cardiology community with copies of the PowerPoint presentations
they made to the FDA.
And, of course, their stocks went down a bit as analysts
saw the extremely lucrative market for drug-eluting
stents begin to shrink. Can you say "a 20% reduction in a $6 billion
annual market equals $1.2 billion"?
However, all's good now....
Today's New York Times announced, "Street
Expresses New Confidence in Drug-Coated Stents". The
"Street", of
course, is not the one you live on, but where
stock analysts dwell, and where they now are feeling optimistic
that drug-coated devices will still account for 75-80%
of the stent
market.
What does this mean for patients? Well, the article
is not in the Health section, but in the Business section. Interestingly
enough, the article ends
with:
It seems farfetched that drug-coated stents could
fall that far [to 40%]. Unless, of course, there is more bad news about
clotting risks.
Perhaps not so farfetched if patients who are
about to have an intervention and have read the news today oboy and
don't particularly want to
risk a stent thrombosis in two years and don't like the idea of taking
Plavix for a year or two or life, if those patients spend a few
extra minutes in their cardiologist's office discussing this, and
their cardiologist determines that maybe after all this
patient is at low risk for
restenosis, or won't be compliant with the Plavix/aspirin combo,
so why not just go with a bare metal stent. Maybe that might have an
effect on "the Street".
After all, at its worst, the
restenosis rate with bare metal stents was 20%. The closer cardiologists
come to predicting who that 20% might be, the less important the
drug-coated stent will become. Dr. John Spertus of the Mid-America
Heart Institute in Kansas City told me a few weeks ago that probably
60% of patients would benefit from drug-eluting stents. Dr. Sanjay
Kaul of Cedars-Sinai in L.A. thinks it's more like 40%.
We welcome your opinion. After all, when the data
are lacking, your guess is as good as anyone's.
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