DOLPH
HUTTER, MD: Hello, I'm Dolph Hutter. Welcome to the
American
Joining
me to discuss the topic are Dr. Deepak Bhatt, an interventional cardiologist at
the Cleveland Clinic Foundation; Dr. James Tcheng,
Associate Professor of Medicine at
DOLPH
HUTTER, MD: Listen, I think this is
going to be an exciting topic. Let's start out now, just to tell the audience
what we're going to do, I'm going to ask Jim to first of all define what we're
talking about in terms of a non-ST elevation MI, then I'm going to ask Deepak
to define how do we stratify patients.
Then I'm
going to ask Deepak to tell us how we risk-stratify these patients. And then
I'm going to ask Glenn to say, if we do have a PCI option, how do we decide who
needs to go to PCI?
So let's
start out. What is the definition of what we're talking about?
DOLPH
HUTTER, MD: So, Jim, let's start off
with a definition of NSTEMI.
JAMES
E. TCHENG, MD: Great. NSTEMI is the
acronym for non-ST elevation myocardial infarction, which also goes by a
perhaps larger term, the acute coronary syndromes. I think the first place to
start off with is that this is an enormous problem. If you look at just the
number of hospital admissions every year for patients with chest discomfort, I
think we realize that this is one of the leading problems in American health
care. If you take the million-plus emergency room visits and then divide those
patients out into who has an acute coronary syndrome, you're probably talking
at least about 20 to 30% of patients who present with the emergency room
admission diagnosis of chest discomfort.
And yet,
it's clearly not just everybody with chest discomfort.
DOLPH
HUTTER, MD: Right.
JAMES
E. TCHENG, MD: This is a high-risk
group of patients, patients who have a mortality of perhaps 5 to 10% over the
first 30 to 60 days. These are patients defined as new onset discomfort, as
existing…
DOLPH
HUTTER, MD: New onset of, say, chest
discomfort consistent with angina, right?
JAMES
E. TCHENG, MD: Absolutely.
DOLPH
HUTTER, MD: Okay.
JAMES
E. TCHENG, MD: New onset. It could
also be preexisting known coronary artery disease with a change in your
syndrome.
DOLPH
HUTTER, MD: A very important point.
So previous stable angina, but all of a sudden an exacerbation of it in the
absence of precipitating events.
JAMES
E. TCHENG, MD: Correct. It can also
be an expression that is perhaps misleading, for example, a worsening of heart
failure that is actually based on an anatomic basis worsening of coronary
artery disease.
The
underlying pathophysiology is really the key point
here, and that is our understanding that it represents an active lesion,
ruptured plaque and ulcerated vessel that has created some thrombus on top of
it that then leads to a new or altered presentation of typical coronary artery
disease.
DOLPH
HUTTER, MD: Okay. So this person
come into the EW. We should remind all of us, I guess, don't forget, women
often don't present with classical chest pain. They'll have other symptoms, and
you have to think of it.
Now, what
should we do once they're in the EW? Deepak, how do you evaluate these people,
and how do you risk-stratify them?
DEEPAK
BHATT, MD: Well, you know, that's
really a key question, risk stratification, and something that's been the focus
of a lot of research efforts. I think the biggest breakthrough in terms of
diagnosis of acute coronary syndromes in general, and NSTEMI in particular, has
been the development and widespread adoption of troponin.
So if a patient comes in with a chest pain syndrome, and as you rightly just
pointed out, it might even be somewhat atypical symptoms, especially in elderly
and/or female patients. But a syndrome where it is concerning for coronary
ischemia, measurement of troponin should be one of
the first things done, along with an ECG.
DOLPH
HUTTER, MD: Right.
DEEPAK
BHATT, MD: And those two, I think,
are the key risk stratification tools as far as objective evidence in terms of
determining how high risk an acute coronary syndrome this is. Presumable, just
with the history, we've already established that there's enough concern to
label it a type of acute coronary syndrome. But the question now…
DOLPH
HUTTER, MD: I'm sorry to interrupt,
but let me just…when you mentioned the EKG, I think it's very important that
everybody understand that an EKG during pain is extremely helpful. It tells you
if you do have ST segment changes, how extensive they are, where they are, and
if there are no changes during pain, it makes you think, "Well, maybe this
is not coronary."
DEEPAK
BHATT, MD: Absolutely. And the time
to getting that EKG is something that's pretty important, and increasingly
something which I think physicians and emergency departments will be graded by.
So a rapid ECG, measurement of troponin, perhaps
bedside point-of-care testing of troponin. And then
there's an immediate sort of risk stratification that's possible, just from
those two pieces of data.
Beyond
just a troponin and ECG, the TIMI risk score is something
that the TIMI group has developed that has been now validated as an independent
predictor of risk. And what this consists of, just to go through quickly, are
seven independent predictors in patients presenting with acute coronary
syndromes: age greater than or equal to 65 years, the presence of three or more
classic coronary artery disease risk factors, a known prior coronary stenosis greater than or equal to 50%, aspirin use in the
last seven days, two or more anginal events in the
past 24 hours, and then, as I'd already mentioned, ST changes or elevated
biomarkers.
So those
seven different factors are independent predictors, and if a TIMI risk score
adds up to about 0 to 2, that's considered lower risk;
DOLPH
HUTTER, MD: Okay, that's very
helpful. Thank you. So we have EKG changes, pretty objective, and very
important to get that right away. The fastest troponin
screen, you can get it right away. A clinical evaluation, as you just said,
with the TIMI risk factors. Anything else?
DEEPAK
BHATT, MD: Well, first of all, with
the risk, I tend to, in my mind, lump moderate and high-risk together. Most
doctors like to think in sort of in a binary fashion. So in my mind, I either
make them lower risk or higher risk.
And as
far as other factors that are important, even if the initial troponin is negative, it's important to realize that if a
clinician's gestalt is that this is the real thing, real chest pain, to still
treat it aggressively. And certain factors, such as prior revascularization,
congestive heart failure on presentation, patients with diabetes or renal
insufficiency, these often are markers that, even if that initial troponin is negative, if the story is good it probably is
the real deal.
DOLPH
HUTTER, MD: All right. You know, by
the way, when I'm dealing with my patients, I always try to remind them what
their angina felt like before, before surgery or whatever, so if they come in
the emergency ward and say, "Doctor, this is just like I had before my
open-heart surgery," if patients can tell us that, that does help the EW
personnel.
DEEPAK
BHATT, MD: Absolutely. That's a
terrific point.
DOLPH
HUTTER, MD: Glenn, let's say we got
this patient in here, and he's got ST changes, his troponin's
up. I mean, classical risk factors. If we had the option to go to PCI versus
intensive medical therapy, what would be the better option of those two, if you
had both of them available?
GLENN
N. LEVINE, MD: Well, I think Deepak
has made my job a lot easier by discussing those high-risk factors, and I think
most, if not all, cardiologists would agree that at this point in 2004 there's
good data that in patients who have the high-risk markers that he discussed,
namely, a positive troponin, ST depression or a high
TIMI risk score, we have fairly good data from now numerous trials that a
strategy of early catheterization and revascularization is superior to medical
therapy alone, most prominently in those with positive troponins.
In the
TACTICS study by Chris Cannon, there was a 10% absolute, not relative, but
absolute difference in adverse events between those who went to the cath lab early and those who were initially managed
medically.
DOLPH
HUTTER, MD: Yes, but that…
GLENN
N. LEVINE, MD: But clearly…
DOLPH
HUTTER, MD: I'm sorry. Go ahead.
GLENN
N. LEVINE, MD: So clearly, if
someone has both positive troponins and ST
depression, I don't think there would be much controversy that early cath and revascularization is a well-established superior strategy
in that particular patient.
DOLPH
HUTTER, MD: Yes, I would agree. And
I'm sorry for interrupting, but I think that that is just superb. Do you all
agree on this? Deepak and Jim, do you agree with that statement?
DEEPAK
BHATT, MD: Oh, absolutely. 100%.
DOLPH
HUTTER, MD: Yes.
DEEPAK
BHATT, MD: I think at this point in
time the data are really overwhelming favoring an early invasive strategy in
high-risk patients.
DOLPH
HUTTER, MD: And Jim, what do you
think?
JAMES
E. TCHENG, MD: Yes, I agree.
DOLPH
HUTTER, MD: Oh, okay.
JAMES
E. TCHENG, MD: There are additional
data, for example, the ISAR-COOL study, which demonstrated that a period of
pretreatment with, for example, a glycoprotein IIb/III
antagonist, although it helps suppress events, really does not supplant or is
not bettered by an early invasive strategy. So we have TACTICS. We have
ISAR-COOL. Every piece of data we have speaks to early intervention.
DOLPH
HUTTER, MD: So pretty strong
information that we really should move to the cath
lab.
Now,
Glenn, I'm going to come back to you, because I'm in your hospital and I've got
the cath lab right there. That's wonderful. That's
great. Suppose I'm not in your hospital, but I'm in a hospital close by.
There's a certain -- How do you make the decision whether or not to move this
patient into the cath lab, even if you're going to
have to put him in an ambulance?
GLENN
N. LEVINE, MD: Well, I think first,
as Jimmy pointed out, non-ST elevation is a distinct entity. The decision is a
little bit different than ST elevation MI, where we're talking about immediate
transfer for primary angioplasty. In our situation of non-ST elevation acute
coronary syndrome, there's certainly less data that we need to immediately
package this patient and rush him emergently into our cath
lab.
In such a
patient, I think it would be reasonable to initially treat with the medications
that are used in high-risk patients, such as the IIb/III's.
DOLPH
HUTTER, MD: Yes, we'll discuss that
next. Yes, right.
GLENN
N. LEVINE, MD: But in a patient who
has positive troponins an ST depression, it would be
very reasonable and probably appropriate to transfer this patient to a facility
that does do angioplasty.
DOLPH
HUTTER, MD: Assuming that, let's
say, you can get there within an hour or two hours, or is there a time limit,
do you think? Or you're going to start the medical therapy anyhow, but what
would you say about that?
GLENN
N. LEVINE, MD: Well, I would say, as
far as your medical therapies, and I'm sure Jimmy would agree, since there's
good data on IIb/IIIa's, both in ACS and in patients
going to the cath lab for angioplasty, particularly
high-risk patients. It would be very reasonable to start the IIb/IIIa on presentation in the emergency room, regardless
of whether it'll be one hour or two hours or three hours before the patient
hits the catheterization lab.
DOLPH
HUTTER, MD: And then would you call
your referral hospital and say, "I've got this guy. I want to send him
in."
GLENN
N. LEVINE, MD: I would. Again, I
don't think that, unless the patient is having active chest pain with dynamic
ST depressions in front of your eyes, in which case I would emergently take the
person to the lab, I don't think we have data that this person needs to be
emergently taken to the lab.
DOLPH HUTTER,
MD: Well, that's a good point.
GLENN
N. LEVINE, MD: Versus, say, urgently
taken to the lab.
DOLPH
HUTTER, MD: All right. That's a good
point. So if a guy comes in at
GLENN
N. LEVINE, MD: I think that's
appropriate, and I don't think we have any data at this point that for a non-ST
elevation ACS patient who is not having active chest pain, that he needs to be
emergently taken to the cath lab.
DOLPH
HUTTER, MD: Okay. Now, Jim and
Deepak, let me ask you this. We've got this guy. He's at an outside hospital.
He's got ST changes, ST depression, positive troponin.
He's quieting right down. We're going to put him on all the medicines that
we're going to talk about. Let's say he quiets down beautifully. His EKG
normalizes. Would you still want to send him to a center and have a cath at some time, or would you do an exercise test? What
do you think in that situation? How do you make that decision? Jim, do you want
to start?
JAMES
E. TCHENG, MD: Yes. I think we have
a fair amount of clinical trials data that have at least indirectly addressed
this question, and it's remarkable how consistent the information is. If you
look at, for example, CURE, which is a trial in clopidogrel;
PURSUIT, which is a trial of eptifibatide; ISAR-COOL,
which is a trial of tirofiban. All of these trials
show that the longer that you wait for diagnostic catheterization and
definitive revascularization, the only thing that occurs is continued accrual
of event, including mortality events.
So I
would argue that in this patient, even if it cooled down, the standards of
therapy, in fact, the ACC/AHA guidelines suggest that early catheterization is
clearly indicated. It does not necessarily need to be on an emergency basis, as
Glenn has mentioned, but this patient does need to have their anatomy defined and
the intent for revascularization at least embraced.
DOLPH
HUTTER, MD: Okay, very good. So,
Deepak, do you agree with this? Okay.
DEEPAK
BHATT, MD: Yes, I think Glenn and
Jimmy are right on the mark. Really, the bulk of data support an early invasive
strategy. Exactly how early, there is some ongoing investigation to see whether
even earlier is better. But for right now, I'd say in a stabilized patient
within 48 hours or so is an appropriate time frame.
DOLPH
HUTTER, MD: Super. And just for my
own two cents, I totally agree. If you've got objective evidence, you never
know when they're going to heat up again. I would stabilize them. If they're
stable, get them into a setting where they can get an angiogram at the
appropriate time. And of course, if they're having ongoing point, then I think
it does become an emergent situation.
Okay, now..I'm sorry. Go ahead.
JAMES
E. TCHENG, MD: This actually reminds
me of a quote from Yogi Berra. I hope I get the quote
right. But if I remember, it goes something like this. "If you don't know
where you are going, chances are you will end up somewhere else." In that
inimitable way.
DOLPH
HUTTER, MD: That's great. God bless
Yogi Berra. That's super.
Okay,
now, listen. I'm in the hospital now. I just can't get a patient there to the,
well, I'll tell you what. Let me back up. I'm going to say, either one of these
settings, I'm going to start medical therapy. Now, who wants to start? What are
the basic principles of medical therapy? Jim, do you want to start?
JAMES
E. TCHENG, MD: Yes. I think that the
work that's been done over the past decade has been quite remarkable in
identifying antithrombotic therapies as really the
mainstay of early treatment, that although we like to believe that symptomatic
treatment, for example, nitrates, morphine, beta-blockers, actually reduce
mortality and improve outcomes. It turns out that the antithrombotic
environment has really been the best…
DOLPH
HUTTER, MD: Is critical.
JAMES
E. TCHENG, MD: …provided the best
evidence.
DOLPH
HUTTER, MD: Okay. Now, antithrombotic. Heparin or low molecular weight heparin? If
low molecular weight heparin, which one?
JAMES
E. TCHENG, MD: Well, until the
recent SYNERGY trial, I would have said low molecular weight heparin clearly
has the advantage, and particular enoxaparin over unfractionated heparin. SYNERGY does not say that it
doesn't. It just, in all honesty, I believe that SYNERGY clearly demonstrates
that you shouldn't cross over, that you should decide what you're trying to
treat that patient with, that is, low molecular weight heparin versus an unfractionated heparin, and stick with it.
If you go
by the metaanalysis route, it still favors, at least
weakly favors, a low molecular weight heparin approach.
DOLPH
HUTTER, MD: Okay.
JAMES
E. TCHENG, MD: What has to be
considered, though, is the referral, early referral to the cath
lab and the downstream effects of upstream low molecular weight heparin have.
DOLPH
HUTTER, MD: Okay. Glenn and Deepak,
heparin? Low molecular weight heparin? Quickly.
GLENN
N. LEVINE, MD: I agree with Jimmy
that SYNERGY is a little less impressive than previous studies. I think it also
is going to depend on the interventionalist who the
patient is being referred to. If it's an interventionalist
comfortable with using enoxaparin in the lab, then I
would lean towards enoxaparin unless the patient is
going to the lab within several hours of presentation.
DOLPH
HUTTER, MD: Very, very good point.
Glenn. Glenn, what do you think?
DEEPAK
BHATT, MD: Well, actually, Deepak. I
think that, you know, the points Jimmy and Glenn raised about SYNERGY and enoxaparin are all accurate. I think if it's, though, a
hospital, especially one where the patient might be sitting around for a day or
two, probably still the older data, TIMI-11B, ESSENCE, enoxaparin
specifically as a low molecular weight over unfractionated
heparin.
DOLPH
HUTTER, MD: Okay. So you all make a
good point. You know, antithrombotic, important. Work
it out locally in terms of what's the best way to go with your situation there.
Now, what
about antiplatelet therapy? I assume we would all
give these people aspirin. Is that correct?
JAMES
E. TCHENG, MD: Yes, I think that's a
given situation but would not give the patient aspirin, antiplatelet
aspirin.
DOLPH
HUTTER, MD: All right. So we're
going to give, not talking about 100, about 81(mg). Now we're talking about at
least 162, probably 325(mg). What dose do you guys use?
DEEPAK
BHATT, MD: Well, I, myself, go with,
for the acute setting, 325, chew and swallow.
DOLPH
HUTTER, MD: Yes.
DEEPAK
BHATT, MD: And I do that even if the
patient says they took aspirin. Unless it's clearly documented that they've
been given aspirin by medical personnel, I give 325.
DOLPH
HUTTER, MD: Do you all agree? 325 or
162?
GLENN
N. LEVINE, MD: We typically use 325.
DOLPH
HUTTER, MD: Okay.
GLENN
N. LEVINE, MD: And in fact, we've
empowered our nurses in the emergency room to go ahead and give it without a
doctor's order.
DOLPH
HUTTER, MD: Now I want to get to clopidogrel, and also IIb/IIIa.
What about IIb/IIIa? Everybody should get it if they
have those risk factors? Who? Anybody.
JAMES
E. TCHENG, MD: I think it's a, this
is Jimmy, I think the place to start off with is to return to Deepak's comments
about risk stratification. The remarkable thing about the IIb/IIIa
trials is that the benefit of the IIb/IIIa's really
appear to be most pronounced in patients who have either positive markers,
particularly troponin, and/or ECG changes, obviously
in the right setting.
DOLPH
HUTTER, MD: Right. Now, if they have
them, they have those two markers, would everybody say start a IIb/IIIa?
GLENN
N. LEVINE, MD: Yes.
DEEPAK
BHATT, MD: I think if they have both
markers then they're quite appropriate. And you have a good data set to support
that.
DOLPH
HUTTER, MD: Okay. And that's kind of
a unanimous feeling, then, amongst our guests here, and I think pretty well
around the community, you ought to start that.
What
about clopidogrel? Now, let's say you give 300 mg a
load. You know, you go to the cath lab. That's great
if you can do PCI, but if you say, "Oh, my heavens, we've got to go to the
OR," is that a problem? Should we start clopidogrel
in addition to a IIb/IIIa? If so, should we load them
before the cath, et cetera? What do you guys think?
JAMES
E. TCHENG, MD: Well, Dolph, this is the area where there is the least clarity of
all of the antithrombotics.
DOLPH
HUTTER, MD: That's why I'm asking
you guys.
JAMES
E. TCHENG, MD: This is a tough one.
I think we have to reflect upon the available clinical trials data,
particularly the CURE study. But we also have to keep in mind that in CURE
there were substantial delays to cardiac catheterization.
DOLPH
HUTTER, MD: Yes.
JAMES
E. TCHENG, MD: And even after that,
when the patient had surgical anatomy, there were additional substantial
delays.
So the
question in the American environment, where the whole mantra is to get the
patient to the cath lab as quickly as possible, you
know, the title of our presentation this morning is "Emergency
Angioplasty," I think that there are those who would believe, in fact, in
our institution, where clopidogrel is typically not
given until the anatomy is defined, mainly because of the 5 to 10% of patients
who are going to undergo bypass surgery…
DOLPH
HUTTER, MD: Yes.
JAMES
E. TCHENG, MD: …perhaps the day
after that.
DOLPH
HUTTER, MD: We tend to do the same
thing at the Mass General Hospital. We kind of hold off on that until we make
sure what the anatomy is going to be. What about the other two institutions?
What do you do locally?
DEEPAK
BHATT, MD: Well, you know, my own
feeling is that the CURE data are pretty strong and show a benefit across TIMI
risk score.
DOLPH
HUTTER, MD: That's true. Yes.
DEEPAK
BHATT, MD: Unlike the IIb/IIIa inhibitors, which only shine in higher-risk
patients.
DOLPH
HUTTER, MD: Right.
DEEPAK
BHATT, MD: So, you know, I think
perhaps from the patient perspective, in terms of reducing ischemic events,
getting that clopidogrel loading dose in the ED is
the right way to go.
Having
said that, you know, at the Cleveland Clinic we've always been an institution
with a rich surgical history, and our surgeons get upset when we pre-treat,
when those patients end up showing up on their operating room table.
DOLPH
HUTTER, MD: What do you do then?
DEEPAK
BHATT, MD: So it's a tough issue.
DOLPH
HUTTER, MD: What do you do?
DEEPAK
BHATT, MD: Well, you know…
DOLPH
HUTTER, MD: Do you give 300, or just
bring them right to the cath lab and then decide?
DEEPAK
BHATT, MD: In part, it'll depend on
timing to the cath lab, so I think it's got to be
individualized. I think, much like the enoxaparin
question, if the patient is in a health care system where there's going to be
perhaps a substantial delay to catheterization and even though all of us on the
call here today work at institutions where pretty rapid catheterization and
revascularization occurs, that's really not the reality in the United States,
and certainly the rest of the world.
DOLPH
HUTTER, MD: Good point.
DEEPAK
BHATT, MD: Patients end up sitting
around in the hospital for quite a while, so I think the value of medical
therapy, especially in those situations, where rapid revascularization is not
going to occur, I think medical therapy is even more important.
DOLPH
HUTTER, MD: Okay, so good point. If
you're going to go right to the cath lab, you know,
you might hold off. But if it's going to be a delay, you might want to get it
started. And who hasn't commented on this?
GLENN
N. LEVINE, MD: Yes, this… I would
first…
DOLPH
HUTTER, MD: Glenn, yes. Do you agree?
GLENN
N. LEVINE, MD: Yes, I'd first agree
with Deepak. I think it's important to emphasize to people who will be viewing
this program that clearly this is the area where there's least agreement among
cardiologists, particularly in the academic community. I would just address a
couple things.
DOLPH
HUTTER, MD: We're going to have to
wrap up.
GLENN
N. LEVINE, MD: People have already
talked about CURE, but you mentioned, would you add Plavix
in addition to a IIb/IIIa? And in CURE, the main
study where we quote the benefits of Plavix, very few
people receive IIb/IIIa's. In fact it was…
DOLPH
HUTTER, MD: Very good point. It's a
good point.
GLENN
N. LEVINE, MD: Are not, not utilized
at all. So there really is no randomized data. If you give a IIb/IIIa, it's of clinical benefit to additionally give Plavix.
DOLPH
HUTTER, MD: All right. And you
handle it pretty much the same way. You make an individual decision, depending
on the timing of the cath, et cetera?
GLENN
N. LEVINE, MD: Yes, we do. We
usually, again, wait until the anatomy is defined.
DOLPH
HUTTER, MD: Yes.
GLENN
N. LEVINE, MD: And I actually looked
at the amount of patients with ACS who go to CABG during their index
hospitalization over the last decade. We looked at every randomized trial and
every registry, and it turns out it's about 13% of patients.