ASPIRIN RESISTANCE
Is your aspirin therapy working?
Welcome to the Clinician's Roundtable on ReachMD XM160, The
Channel for Medical Professionals. I am Dr. Larry Kaskel, your host and I was
recently at the Aspirin High-Tech Prevention summit and had a chance to sit
down with Dr. Wayne Peters, who is the Medical Director of HealthMark and
Assistant Clinical Professor of Medicine And Preventive Medicine and Biometrics
at the University of Colorado School of Medicine and we talked a little bit
about what aspirin resistance is and how to test it.
DR. LARRY KASKEL:
Dr. Peters, welcome to the Clinician's Roundtable.
DR. WAYNE PETERS:
Thank you very much.
DR. LARRY KASKEL:
Let's start with a little bit of history on aspirin, how long
it's been around, who started it, and how it has changed over the last 100
years?
DR. WAYNE PETERS:
Well aspirin was actually identified or code invented back
in 1900. It is a product of Germany and it was first available or marketed in
the early 1900s in the United States. Well aspirin has gone through many, many
decades of use and more recently many decades of sort of scientific examination
and I think it's safe to say that most Americans now and certainly most of the
medical community realize that aspirin has some definite values in the
prevention of cardiovascular events at least in intermediate and high-risk
patients.
DR. LARRY KASKEL:
Let's talk a little about the pathway and really where
aspirin exerts its primary effect.
DR. WAYNE PETERS:
Well since most vascular events, heart attacks and strokes,
are caused by blood clots. The whole idea has been how can we lessen someone’s
risk of having a blood clot, they don’t need. We do need blood clots if we cut
ourselves or have injuries, but the most part, many of us particularly have
blockages in our arteries or diseased arteries have unnecessary clots. So,
aspirin works on the platelet, which is responsible for the clotting of blood
and it reduces the ability of that platelet to form a clot, if you really don’t
need one.
DR. LARRY KASKEL:
All right, so let's get into aspirin resistance. How common
is it and what are the consequences thereof?
DR. WAYNE PETERS:
Since we recommend aspirin to people who are intermediate or
high risk of having heart attacks or strokes either because they've already had
one or because their cholesterol or blood pressure or either they have
diabetes. People have looked at the whole concept does one size fit all when
it comes to aspirin, and as they started looking at it through a variety of
blood tests or more recently a urine test, they realized that somewhere between
5 to 40% of the population is resistant to at least the low doses of aspirin
and a variety of reasons are present as to why that might occur. It has raised
the whole spectra then. If we are truly trying to prevent a heart attack or
stroke, may be we need to look and see, who might be aspirin resistant and who
isn't to maximize our prevention efforts.
DR. LARRY KASKEL:
So, that’s a pretty big numbers. So, potentially we are
giving our patients aspirin and thinking everything is fine and they subsequently
go on and have an event and we never even thought of checking to see if the
medicine we are giving them is actually doing something. So, in primary care,
what can I do to confirm that my patient is getting the benefit of the aspirin
and it is actually working?
DR. WAYNE PETERS:
I think the easiest thing in primary care is to order an
aspirin resistance test from the urine because all that patient has to do is
submit a sample in a cup, which is given to the laboratory, it is sent off for
an analysis and you get a quick reading on is the aspirin adequately
suppressing the platelet function in this patient. Now there are other kinds
of test that you can do where you draw blood and has to be in a very orderly
fashion and then send it to the laboratory. The problem with that is nobody
really likes to get their blood drawn if they don’t really have to and so with
the simplicity of the urine test, I can really tell someone with reassurance on
whether the current dose of aspirin you are taking is being sufficient to
lessen their platelet function and lessen their risk of blood clot.
DR. LARRY KASKEL:
Wayne, what screws up aspirin absorption or what messes with
it’s working well?
DR. WAYNE PETERS:
Well one of the most common things that happens when someone
takes anti-inflammatory medications for arthritis or headaches or whatever sort
of pain, more particularly ibuprofen, which is Motrin or Advil or other common
brands is that type of medication can compete with the aspirin on the platelet
and interfere with its benefit on reducing blood clot risk. So, if someone is
going to take ibuprofen and aspirin, they need to take the aspirin first thing
in the morning, wait 30 to 45 minutes, then take the ibuprofen through the rest
of the day as directed, but they need to give the aspirin a chance to do its
things before they potentially interfere with that effect by taking ibuprofen.
DR. LARRY KASKEL:
And besides the other nonsteroidals what else can create
aspirin resistance?
DR. WAYNE PETERS:
Well just having high cholesterol, high LDL-cholesterol in
and of itself can do that, can interfere with the benefits of aspirin and it
may have to do with reasons why that person has a high cholesterol in the first
place, some of those are genetic, many of them are lifestyle. Smoking
cigarettes can interfere with the effectiveness of aspirin as well as can
certain types of medication. Now lot of this is very preliminary and we don’t
have precise data and exactly, which medications and how much might interfere
for sure we know about the ibuprofen, smoking, and if you do have a high
cholesterol even more important to check for aspirin resistance.
DR. LARRY KASKEL:
If you have just tuned in, you are listening to the
Clinician’s Roundtable on ReachMD XM 160, The Channel for Medical
Professionals. I am Dr. Larry Kaskel, your host, and I was recently at the
Aspirin High-Tech Prevention summit and got to talk with Dr. Wayne Peters, who
is the Medical Director of HealthMark and we were talking a little bit about
aspirin resistance.
Wayne can you talk a little bit about some clinical trials
that have been done that actually look at how urinary thromboxane may actually
predict events like MI, stroke, or death.
DR. WAYNE PETERS:
The whole trial was a very large trial. Thousands of
patients they were looking at a variety of things including using certain types
of blood pressure medications and ACE inhibitors to lessen risk of vascular
events. They did a subset of the whole trial where they actually looked at the
urinary levels of thromboxane, which is what we test for to see if you are
aspirin resistant and it turns out that those people, who had the least
inhibition of thromboxane B2, which is in the clotting cascade, had the highest
risk for MI, stroke, or death from cardiovascular events. It was increased
2-fold over the people who had the greatest response to the aspirin and a
2-fold increase in risk is not insignificant. Many of the risk factors we look
for like high blood pressure, high cholesterol, smoking, etc., are in the 2 to
4-fold increase risk range.
DR. LARRY KASKEL:
Dr. Peters, when we look at high-risk patients, what do we
do with dosing? Do we give him all the same dose to start with, do we give him
a higher dose? How do we going to make that decision?
DR. WAYNE PETERS:
This is recently emerged into a very interesting
discussion. For a long time it was stated that if you take a baby aspirin,
which is 81 mg in this country that, that would probably suffice for most
people. What we now realize is that 81 mg while it works in significant
percent of population, simply isn't enough for many people because of this
whole aspirin resistance story and so is there an ideal dose of aspirin that we
could just say, lets give this to everybody and not worry about it, some people
say well 2 baby aspirin, which is 162 mg or half of the regular aspirin tablet
might be the ideal dose, but I think in a person, who has already had a
cardiovascular event or in a person, who is at high-risk for one, but hasn't
had the heart attack or stroke yet, then we really need to start with 81 and
then check them a couple weeks later and see if in fact we have suppressed
their platelet function to a significant degree or whether we need to then
gradually move up the dose range to appropriately make sure that the aspirin is
doing the job that it is supposed to do. Another thing that can affect
absorption is the whole process of enterically coating the aspirin, therefore
having less potential to cause GI side effects because if someone is going to
have a major effect from aspirin, it is in their intestinal tract and
occasionally people get bleeding from their stomach, which rarely can be
life-threatening and so I think being thoughtful about how much you need and
only using as much as you need is the important way to go here and that if it
is an enteric-coated preparation, which may be easier on the stomach along with
taking the aspirin at the time of a meal, then again we can gradually titrate
the dose up, use the exact dose if they need for the prevention and hopefully
minimize the risk of having any problems with bleeding in the stomach.
DR. LARRY KASKEL:
Wayne, tell me a little bit about the test what it's called,
how we go about ordering it in our patients?
DR. WAYNE PETERS:
Well, this urinary test has got an easy name for it. It is
called AspirinWorks and it's through a company called Corgenix. It should be
available at your local laboratory either lab core or quest. All the doctor
would really need to do is ask the person, who is drawing the blood or getting
the urine specimen to order an AspirinWorks that company provides small plastic
tubes that the urine needs to be put into transmit to the laboratory and then
it is coated for prevention of vascular events and usually it's my experience
that we've not had any difficulty in having it reimbursed. So, the key thing
here is if the lab that the physician isn't really familiar with the
AspirinWorks test, just to make sure that a representative has dropped off to
the draw station or the doctor’s office the tubes that have AspirinWorks label
on them so that it will preserve the urine in such a way that it can be
analyzed and give a correct answer.
DR. LARRY KASKEL:
We talk a lot about the risk reduction of taking an aspirin
being about 33%. We also hear the risk reduction of taking the statin is about
33% and it seems that everyone's on a statin and an aspirin, but yet we are not
getting a 66% reduction. Can you comment on that?
DR. WAYNE PETERS:
Well your question really has to do with what's called
residual risk. It is that no matter what sort of therapy we have used, it
almost always reduces the risk of a heart attack or stroke or cardiovascular
death by about 33% and what that has made us realize is that he don’t just give
somebody a statin cholesterol medicine and say you are fine, your LDL
cholesterol is under 70, you have no more risk for heart disease. What we have
to do is a thoughtful combined approach. They need to be on a statin. They
need to be on aspirin for sure, probably some fish oil. They need to have
their blood pressure well controlled. They need to have their HDL cholesterol
at least 45 or 50 in a man and 55 or 60 in a woman. They probably need to have
their triglycerides lower. They need to lose weight. They need to quit
smoking and you put all of those things together and may be some day we really
can reduce the risk of having heart attack by 80% to 90% and so it's a
combination effort not just take this pill and you will be free. So, I think
Tim Russert was a classic example of that. He was taking a statin medication.
His LDL cholesterol was under 70. People thought well may be he is at lower
risk, but many of the other things were probably still present and may be not
maximally treated and so it’s a combination approach not just a single-issue
approach for this.
DR. LARRY KASKEL:
Dr. Wayne Peters, thank you very much for talking with me
today.
DR. WAYNE PETERS:
Thank you very much.
DR. LARRY KASKEL:
I am Dr. Larry Kaskel and you have been listening to the
Clinician’s Roundtable on ReachMD XM 160, The Channel for Medical
Professionals. Please visit our website at reachmd.com, which now features our
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