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February
19,
2010 -- 6:35pm EST
Plavix After Stents: How Long?
I
recently interviewed
Dr. Eric Topol for Angioplasty.Org about
current efforts to determine the optimal duration of dual antiplatelet
therapy (a.k.a. DAPT or clopidogrel plus aspirin) after drug-eluting
stent placement. My first question was what had we learned about
this issue since the 2006 FDA stent safety hearings? And his
answer was "Unfortunately, we don't know anything more...".
Sort of shocking. A major study was supposed to
come out of those hearings, but the
DAPT study just began recruiting last summer and won't be completed
for four years. This massive study, sponsored by all the major
stent makers, as well as the manufacturers of antiplatelet meds,
will enroll 20,000 patients and test them at 12 and 30 months to
determine the rates of MACCE (death, heart attack and stroke)
stent thrombosis and major bleeding complications. It will be performed
with all
drug-eluting stent brands and will not compare one to another.
What will this teach us? Dr. Topol has an opinion about the DAPT
study:
"The notion that we should treat all patients
for X duration is totally crazy. It completely goes against
all the evidence that every patient is an individual with a
separate biologic story, and a risk of bleeding. And then there
is obviously a big expense. The drug companies would love it
to be 30 months or 30 years. But to try to generalize from
a trial like that, I'm amazed that it's going forward."
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Dr. Topol (who, by the way, was an invited panel
member at those 2006 FDA hearings) is currently Director of the
Scripps Translational Science Institute (STSI) where he is conducting
research on the genomics of coronary artery disease. The bottom
line is that all patients are not the same -- and they respond
to antiplatelet therapy differently. So Dr. Topol believes that the
"one-size-fits-all" concept of thrombosis prevention just doesn't
apply.
Another concept is that all drug-eluting stents aren't
the same. Because of the metal structure, polymer coating or drug
itself, each device
has different characteristics and different healing properties. This
was seen clearly in the ODESSA
trial, where Dr.
Giulio Guagliumi used OCT intravascular imaging to measure stent
coverage at six months. He found significant incomplete coverage
in the CYPHER and
TAXUS stents, but complete healing in the ENDEAVOR.
As a result of these findings and other clinical data,
two trials, involving only Medtronic's ENDEAVOR stent, are currently
starting up: SEASIDE, which Dr. Topol is involved in, will measure
the outcomes of patients
who receive and only get six months of DAPT;
and OPTIMIZE,
being
conducted in Brazil by Dr. Fausto Feres, which is stopping DAPT
at
three months.
Rather than testing if DAPT is more effective at longer
durations, such as 12 and 30 months, these studies are testing to
see if it is just as
effective at shorter periods, when used with a DES that has a greater
healing profile, like the ENDEAVOR. The advantages of a shorter DAPT
duration are several:
- less risk of bleeding complications (inherent
in the use of antiplatelet drugs);
- less cost (Plavix costs $4/day
-- the difference of a year or two is significant -- newer
antiplatelet drugs like prasugrel cost even more);
- less problems deferring surgery (in order to perform
surgery of any sort, for example knee replacement, etc., antiplatelet
therapy
must be stopped).
The short back story here is that when drug-eluting
stents first came on the market
in 2003-2004, the FDA recommended six months of
DAPT to
keep the
blood
from
clotting in and around the stent (a.k.a. stent thrombosis).
Within a couple of years, reports
surfaced about a small number
of patients who suffered late stent thrombosis (six months
or more after stenting). A flurry of concern
arose and the 2006 FDA stent safety hearings resulted in recommendations
to extend DAPT to 12 months or more -- the current guidelines.
But, as Dr. David
Kandzari, co-principal investigator for the SEASIDE trial told
Angioplasty.Org:
"Current treatment guidelines are
based principally on consensus opinion and intuition rather
than
hard evidence that extending DAPT reduces the risk of late
and very late ST. In fact, in more recent trials, patients
experiencing very late ST are more commonly on DAPT than off."
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Dr. Kandzari explores this issue in detail in his Viewpoint article in
December's JACC: Interventions, "Identifying
the 'Optimal' Duration of Dual Antiplatelet Therapy After Drug-Eluting
Stent Revascularization"
For more information, read my interview
with Dr. Topol and keep up with the latest news in our StentCenter.
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