November
2009 Archives:
November 25, 2009 -- 6:15pm EST
Fractional Flow Reserve (FFR) Recognized
in Guidelines, Not So Much In Reimbursement
When
I heard Dr. Nico Pijls first present data from the FAME study
during a press conference at the 2008 TCT, I was struck by
the similarity of the concept to what Andreas Gruentzig,
inventor of coronary angioplasty, was doing in the early
days of balloons: measuring intra-arterial pressures to discern
what exactly was going on inside the coronaries during these
procedures. I brought this up with Dr. Pijls and he agreed.
I've detailed this whole thread back in my January post titled, "FAME:
Back to the Future".
So FAME and the value of Fractional Flow Reserve
(FFR) have now found
their way into the official PCI guidelines. Last week, the ACC/AHA/SCAI
issued their first Focused Updates -- a way of responding more quickly
to recent and important clinical and research information (guidelines
normally are only issued every two to three years) -- and FFR was
included as "useful to determine whether PCI of a specific coronary
lesion is warranted."
The two manufacturers of FFR catheters, Volcano
and St. Jude, feel that functional measurement (FM) is going to be
a rapidly growing field. With the upgrade in the Focused Guidelines
this may be so. But, as usual, reimbursement is lagging behind. Interventional
cardiologists may see the scientific evidence that FFR improves outcomes
but, if there isn't sufficient reimbursement for its use, they will
be less inclined to use it.
Augusto Pichard, MD of Washington Hospital Center
told me he doesn't have this problem because he did an analysis of
how much money was saved by using this technology and his hospital "got
it".
And, as William F. Fearon, MD of Stanford University
Medical Center observed, "Use of FFR technology represents a rare
opportunity in medicine in which an innovative product not only improves
clinical outcomes but also saves money."
Lower costs and a third less heart attacks and
deaths. FFR should be in every cath lab, right? Yet currently
penetration of this technology in the U.S. is only 5%. Comments?
November 17, 2009 -- 11:30pm EST
PPIs and Plavix -- Confusion Reigns Supreme
Patients
taking Plavix (a.k.a. clopidogrel) -- and that would be all
stent patients -- sometimes experience a side effect of gastric
upset, heartburn or even bleeding. So they are given a Proton Pump
Inhibitor (PPI) with a brand name of Prilosec, Nexium, Prevacid
or Protonix to alleviate these symptoms.
In the past a number of observational studies
(namely from Medco and
the Veterans Administration) have shown that patients who take
PPIs and Plavix experience an increased risk of adverse events,
such as heart attacks. However, other studies have shown no clinical
effect. In fact it was only a short while ago that a panel of cardiologists, commented
during this year's TCT meeting on the COGENT trial (COGENT
examined the clinical results of taking Plavix with PPIs). The
panel exclaimed quite pointedly that the COGENT study, a randomized
clinical trial (not a retrospective observational study) was THE study
that revealed the truth -- and that truth was that there was NO
increase in adverse clinical events when PPIs were taken with Plavix.
They even did a Colbert-like "wag of the finger" to the
medical news outlets that published inflammatory headlines about
the non-existent danger.
So it was a bit of a shock to these and other cardiologists
assembled at the American Heart Association Annual Scientific Sessions
in Orlando to read today's warning
from the FDA:
The concomitant use of omeprazole [Prilosec]
and clopidogrel should be avoided because of the effect on
clopidogrel's active metabolite levels and anti-clotting activity.
Patients at risk for heart attacks or strokes, who are given
clopidogrel to prevent blood clots, may not get the full protective
anti-clotting effect if they also take prescription omeprazole
or the OTC form (Prilosec OTC)....
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This warning also mentioned other drugs to be avoided
when taking clopidogrel, such as esomeprazole (Nexium), cimetidine
(Tagamet) and so on.
In addition, yet another observational study about
PPIs and Plavix was presented yesterday at the AHA meeting. This
retrospective study, which looked at patient records from Mt. Sinai
in New York, showed an increase in adverse events. These two provided
a double whammy to the results of the COGENT trial.
So
earlier today I asked Dr. Christopher Cannon about this new study
(two months ago he stated in no uncertain terms that the COGENT study
proved that there was no increased risk for patients when taking
Plavix and PPIs). Dr. Cannon is the senior investigator of the Thrombolysis
in Myocardial Infarction (TIMI) Study Group, and has led some of
the most well-known practice-changing guidelines in the treatment
of heart disease He replied:
These new studies are observational ones
-- with exactly the same flaws as the prior Medco and VA database
studies -- [and] they get the same wrong answer...
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The difference between a randomized clinical trial
(RCT) and a retrospective observational study is an important one
here in understanding the different results. An RCT is a carefully-designed
scientific test of a hypothesis -- patients are randomized to two
different treatments in a way that negates differences in ages, states
of health, and other "confounding" data. An observational
study looks at patient data that already exists. Attempts can be
made to normalize the patient groups for comparison's sake, but the
results are not necessarily accurate when measuring two treatments,
for example. This is why the FDA normally requires that an RCT be
done before a new treatment is approved. Observational studies, however,
can point to possible problems, or can generate hypotheses for future
randomized scientific trials. They can show associations, but not
necessarily prove cause and effect.
This is, in effect, what happened with PPIs and
Plavix, and why the COGENT trial was done: to answer the questions
raised by the early observational studies.
Dr. Chet Rihal, director of the catheterization
lab at Mayo Clinic put it another way (as quoted in HealthDay):
All this shows is that people taking PPIs
have a worse outcome than those not taking PPIs. This does
not prove there's causation. That would be like saying that
carrying matches is associated with lung cancer. It is associated,
but it doesn't mean it causes lung cancer.
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Indeed, one explanation for these different results
is that patients who are having gastric distress and require Prilosec
may be sicker or older patients, thus skewing the results of any
observational study against the group taking PPIs -- they may have
worse outcomes because they started off sicker or older -- and the
worse outcomes are not "caused" by the PPIs.
As for the FDA warning, which involves a label
change to the drug clopidogrel, Dr. Cannon noted to me that it was
more carefully worded, and did not claim that PPIs caused more adverse
events, only that PPIs have been shown to reduce the antiplatelet
effect, something that was shown in a small study last year, titled OCLA
(Omeprazole CLopidogrel Aspirin) -- a study conducted by Dr.
Deepak L. Bhatt, Cannon's colleague at Brigham and Women's in Boston.
Dr. Cannon continues:
But, as we know from COGENT, there is not
a difference in clinical events when combining omeprazole [Prilosec]
and clopidogrel. Thus, as we have seen before, often small
changes in the level of platelet inhibition don't translate
into a clinical effect. The label is careful to stick to the
platelet data. It is reasonable to know of the platelet data,
but the FDA needs to see the COGENT data -- and, of course,
we all need to give much more weight to the randomized trials,
not the confounded observational studies.
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So should you stop taking your Prilosec or Nexium
with your clopidogrel? Most doctors say no -- in fact suddenly stopping
either medication could cause serious problems. However, you should
call or see your cardiologist and ask him or her about these studies.
Meanwhile the FDA has placed this issue on the
agenda for the November meeting of its Drug
Safety Oversight Board and HealthDay reports that new AHA/ACC
recommendations on the use of PPIs with Plavix will be announced
tomorrow (Wednesday) during the American Heart meeting.
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