This is a transcript of an online program, which may be found at:

http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
PCI vs CABG in Multivessel
Disease
Chair
William E Boden MD
Clinical Chief, Division of
Cardiovascular Medicine;
Professor of Medicine and
Public Health,
University at Buffalo Schools of
Medicine & Biomedical Sciences;
Medical Director, Cardiovascular
Services, Kaleida Health;
Chief of Cardiology,
Buffalo General and
Millard Fillmore Hospitals,
Buffalo, NY
Panelists:
Friedrich W Mohr MD
Professor of Cardiac Surgery,
University of Leipzig Heart Center,
Leipzig, Germany
Patrick W Serruys MD PhD
Professor of Medicine
and Interventional Cardiology,
Thoraxcenter, Erasmus University,
Rotterdam, The Netherlands

Slide 1

William E Boden, MD: Hello. Im Bill Boden from the State University of New York at Buffalo,
United States. Id like to welcome you to our Spotlight, "PCI vs CABG Surgery in Multivessel
Disease," in which well discuss the late-breaking and important SYNTAX trial (Synergy
between PCI with TAXUS and Cardiac Surgery) that was presented at the 2008 European
Society of Cardiology Meeting in Munich. Im joined today by the two senior investigators and
study co-chairs of SYNTAX, Professor Patrick Serruys of the University of Erasmus in The
Netherlands, and Friedrich Mohr, Professor of Cardiac Surgery at the University of Leipzig
Heart Center in Germany. Patrick, Friedrich, welcome.







This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
Slide 2
PCI vs CABG Trial Results Summary
Mortality & MI Angina relief
Repeat
revascularization Stroke
GABI
No difference No difference CABG n/a
EAST No difference
CABG CABG No difference
RITA No difference
CABG CABG n/a
ERACI No difference
CABG CABG n/a
CABRI No difference
CABG CABG n/a
BARI No difference
No difference CABG n/a
MASS-II
CABG (MI) No difference CABG No difference
AWESOME No difference No difference
CABG No difference
ERACI-II
PCI n/a CABG n/a
SoS
CABG (mortality) CABG CABG n/a
ARTS-I
No difference n/a CABG No difference
ARTS-II
No difference n/a CABG No difference
MAIN-COMPARE
No difference n/a CABG No difference
LE MANS
No difference No difference CABG No difference
Superior treatment modality
N
o

s
t
e
n
t
s

u
s
e
d
B
M
S

s
t
e
n
t
s

u
s
e
d
CABG PCI No difference
D
E
S

s
t
e
n
t
s

u
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e
d


Obviously, there have been a whole host of randomized trials, at least 15 of them, dating back
to the late 1980s, which have evaluated the respective roles of coronary bypass graft surgery
(CABG) vs percutaneous coronary intervention (PCI). From the outset, I want to congratulate
both of you on the design and the execution of a pivotal trial, a critically important study that
will, I think, reshape the way that we manage patients with stable coronary artery disease
(CAD). In particular, I want to congratulate you on the unique features of this trial, which
involved both a real-world registry and the use of a heart team. I think it was novel in its design
in terms of coming to a consensus about whats best for patients, and thats ultimately what all
of us really desire.

Patrick, Im wondering if you might be so kind as to summarize from your perspective the
highlights of the SYNTAX trial, and perhaps discuss the main findings, and then well discuss
some of the important registry findings.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
71% enroll ed
(N = 3075)
Treatment preference (9.4%)
Referring MD or patients refused informed consent (7.0%)
Inclusion/exclusion (4.7%)
Withdrew before consent (4.3%)
Other (1.8%)
Medical treatment (1.2%)
No f/up
n = 428
5 yr f/up
n = 649
Total enrollment
N = 3075
Stratification: LM and diabetes
Two registry arms
N = 1275
Randomized arms
N = 1800
Heart team (surgeon & interventionalist)
PCI
N = 198
CABG
N = 1077
Amenable for onl y one treatment approach
TAXUS
*
N = 903
CABG
N = 897
vs
Amenable for both treatment options
LM
33.7%
3 VD
66.3%
LM
34.6%
3 VD
65.4%
DM
28.5%
Non DM
71.5%
Non DM
71.8%
DM
28.2%
23 US sites 62 EU sites
SYNTAX Trial Design
*
TAXUS Express Boston Scientific
vs

Slide 3

Patrick Serruys, MD: Youve given a very good introduction, and I think the first thing is to
show the structure of the trial. Its clear that it was run in the United States and in Europe. We
were screening a large number of patients. Up front, we had basically a minimum number of
exclusion criteria, specifically, no previous intervention, and no acute myocardial infarction
(MI), and thats about it. We screened a lot of patients, and we ended up with 71% of the
patients being enrolled. That represented a cohort of 3000 patients. As you said, what was
essential from the very beginning was the concept that the heart team, made up of a surgeon
and an interventional cardiologists, had to judge these cases one by one and decide if both
techniques of revascularization could be applied, or were they amenable only for PCI or only
for CABG. So, the spectrum was complete.

In the randomized arm we had 1800 patients. There was prestratification for left main and
three-vessel disease. In the registry, we had 1275 patients, about 1000 patients for surgery,
and the rest a small cohort for PCI, who were basically inoperable.

What is important to point out is that it was the interventional cardiologist and the surgeon who
together determined which were the surgical cases and these patients were put in the registry.
Patients in the randomized trial were amenable to both revascularization techniques. So, thats
an important point in the structure. We had 28% of diabetic patients in this cohort, and that was
another prestratification.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
Patient Profiling
Local heart team
assessed each patient
regarding:
Patients operative risk
(EuroSCORE & Parsonnet
score)
Coronary lesion complexity
(Newly developed SYNTAX
score)
Goal: SYNTAX score to
provide guidance on optimal
revascularization strategies
for patients with high risk
lesions
Sianos, et al. EuroIntervention. 2005;1:219-227.
Valgimigli, et al. Am J Cardiol. 2007;99:1072-1081.
Serruys, et al. EuroIntervention. 2007;3:450-459.
BARI classification of coronary segments
Leaman score. Circulation. 1981;63:285-299.
Lesions classification ACC/AHA. Circulation. 2001;103:3019-3041.
Bifurcation classification. Catheter Cardiovasc Interv. 2000;49:274-283.
CTO classification. J Am Coll Cardiol. 1997;30:649-656.
Dominance
Serruys P, et al. ESC 2008.

Slide 4

We then developed for the trial, together with Friedrich and many others, the so-called
SYNTAX score because we were concerned about the fact that you have two- and three-
vessel disease. We used different scores, taking into account the dominance of the vessel; the
number and location of lesions; whether it was a left main, three-vessel; the number of total
chronic occlusions, the tortuosity, bifurcation, and the thrombus. It was an amalgam of four or
five different previous scores and classifications so that both of us were forced to look at the
anatomy and foresee the complications -- at least for us interventional cardiologists. That was
part of the work of local heart team, to use the SYNTAX score and to look at the risk in terms
of EuroSCORE and Parsonnet, and then decide if an individual was a candidate for
randomization.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
Patient 1
Patient 1
Patient 2
Patient 2
SYNTAX SCORE 21 SYNTAX SCORE 52
LCx 70%-90%
LAD 70%-90%
RCA2 70%-90%
RCA3 70%-90%
LM 99%
LCx 100%
LAD 99%
RCA 100%
Not All 3-Vessel Disease Is the Same
Serruys P, et al. ESC 2008.

Slide 5

This is an example on the left-hand side. You see a coronary artery with four discreet
stenoses, no involvement of bifurcation, and you have a score of 21. The patient on the right-
hand side has a pinpoint main stem lesion followed by a napkin stenosis in the proximal LED,
the circumflex is totally occluded, and the right is totally occluded, it gives a score of 52. I will
not take this patient. It is a surgical candidate.

Dr Boden: Right.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
SYNTAX Primary Endpoint
Primary clinical endpoint is the 12-month Major
Cardiovascular or Cerebrovascular Event Rate
(MACCE
*
)
MACCE is defined as:
All-cause death
Cerebrovascular accident (CVA/stroke)
Documented myocardial infarction (ARC definition)
Any repeat revascularization (PCI and/or CABG)
All events CEC adjudicated
*
ARC MACCE definition. Circulation. 2007;115:2344-2351.

Slide 6

Dr Serruys: In terms of the trial, the endpoints reflect the patients perspective. We measured
major adverse events, all-cause death, stroke as adjudicated by the neurologist on the critical
events committee, any MI using the new ARC definition, and any repeat revascularization,
regardless if it was for progression of the disease, etc.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
Patient Characteristics (RCT)
Patient-based
CABG
N = 897
DES
N = 903
P value
Total SYNTAX score 29.1 11.4 28.4 11.5 0.19
Diffuse disease or small vessels, % 10.7 11.3 0.69
No. lesions, mean SD 4.4 1.8 4.3 1.8 0.44
3 VD only, % 66.3 65.4 0.70
Left main, any, % 33.7 34.6 0.70
Left main only 3.1 3.8 0.46
Left main + 1 vessel 5.1 5.4 0.78
Left main + 2 vessel 12.0 11.5 0.72
Left main + 3 vessel 13.5 13.9 0.78
Total occlusion, % 22.2 24.2 0.33
Bifurcation, % 73.3 72.4 0.67
Trifurcation, % 10.6 10.7 0.92
Serruys P, et al. ESC 2008.

Slide 7

We can talk a long time about the patient characteristics. I think the only important point is that
two thirds were three-vessel disease, one third left main. The left main is a heterogeneous
group. You could have left main and one-vessel disease in 5%, left main and two-vessel in
12%, left main and three-vessel in 13%. Thats important. 20% to 24% of all patients had at
least one occlusion, and you can see that bifurcation was involved in the revascularization
process in about 70% of cases, with 10% having a trifurcation.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
All-Cause Death/CVA/MI to 12 Months
P = 0.98
*
0 6 12
10
20
0
Months since allocation
C
u
m
u
l
a
t
i
v
e

e
v
e
n
t

r
a
t
e

(
%
)
ITT population
7.7%
7.6%
Event rate 1.5 SE.
*
Fishers exact test.
TAXUS (N = 903) CABG (N = 897)
Serruys P, et al. ESC 2008.

Slide 8

Now, as clinicians, what counts for Friedrich and me is the hard event, the irreversible event:
you die, you have a stroke, or you have an MI, and in both disciplines there was some balance
and imbalance of these three things. But, the bottom line is that if you look at the composite
endpoint of these three irreversible hard events, the incidence for surgery was 7.7% and the
incidence for the PCI was 7.6%. You can read the P value at the top.

Dr Boden: This was a prespecified secondary outcome.

Dr Serruys: Secondary endpoint.

Dr Boden: Let me ask you, when you were designing SYNTAX was some consideration given
to making this the primary endpoint as opposed to the secondary endpoint? What went into the
decision to include myocardial revascularization as part of the primary endpoint? Because that
is something that many individuals may be a bit confused by?

Friedrich Mohr, MD: I think one reason is that if you compare it with previous trials, like the
ARTS trial (The Arterial Revascularization Therapies), where we looked at five-year outcomes
you can see that repeat revascularization had a major impact on how they were valued.
Repeat revascularization was always much higher, and there was a big difference between
rates after CABG and after PCI. In this trial, we knew that survival might be impacted in three-
vessel disease and left main disease. We knew that complete revascularization does have an
impact on patient survival in the long-term and so if repeat revascularization is necessary, it
may have a negative impact too. So, that is why we added it on.





This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease

Dr Boden: Good. The reason I make this point is that many trial purists will look at a study
where the primary endpoint is not met and they will say that everything else is irrelevant, even
if the secondary endpoint is positive. Of course, I do not agree with that interpretation, and I
would agree with you too, Patrick, that what we as clinicians pay the most attention to is the
hard outcomes in terms of death, MI, and stroke reduction. I think to see that the two groups
were essentially superimposable in terms of their event rate over one year speaks volumes
about how PCI fared at least over the short-term. Now for the primary endpoint, which I
assume will be on your next slide.

Staged procedure, % 14.1
Lesions treated/patient, mean SD 3.6 1.6
No. stents implanted, mean SD 4.6 2.3
Total length implanted, mm SD 86.1 47.9
Range, mm 8 324
Long stenting (>100 mm), % 33.2
Procedural Characteristics
PCI Randomized Cohort
TAXUS
N = 903 Patient-based
Serruys P, et al. ESC 2008.

Slide 9

Dr Serruys: Yes, its coming. There is one slide in between. We didnt show the slide with all
of the technical characteristics of these patients, but you must realize that it was 3.6 lesions
treated, 4.6 stents implanted, 86 mm stenting on average, one third of the patients with more
than 100 mm stenting. So, there was somewhere the fear that death, stroke, and MI may have
been influenced by stent thrombosis or graft thrombosis.

Dr Boden: Right.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
Symptomatic Graft Occlusion and
Stent Thrombosis to 12 Months
3.3
3.4
CABG TAXUS
P
a
t
i
e
n
t
s

(
%
)
n = 27
n = 28
ITT population
Serruys P, et al. ESC 2008.
P = 0.89

Slide 10

Dr Serruys: The next slide shows that over a period of one year, documented by angiography
in symptomatic patients, that is patients who end up on the table for a coronary angiography,
we see very similar numbers of stent thromboses. Thats maybe a small detail.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
MACCE to 12 Months
P = 0.0015
*
0 6 12
10
20
0
Months since allocation
C
u
m
u
l
a
t
i
v
e

e
v
e
n
t

r
a
t
e

(
%
)
ITT population
12.1%
17.8%
Event rate 1.5 SE.
*
Fishers exact test.
TAXUS (N = 903) CABG (N = 897)
Serruys P, et al. ESC 2008.

Slide 11

Now, this is the primary endpoint including revascularization. The score of the surgeon was
12.1% and the score of the interventional cardiologist 17.8%, with a P value of 0.0015.







This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
Primary Endpoint: 12-Month MACCE
Noninferiority Analysis
0 5% 10% 15%
Prespecified margin = 6.6%
Difference in MACCE
20%
+95% CI = 8.3%
The criteria for noninferiority comparison were not met for the
primary endpoint; further comparisons for the LM and 3 VD subgroups
are observational only and hypothesis generating.
5.5%
Serruys P, et al. ESC 2008.

Slide 12

The way we handled the primary endpoint was as noninferiority. So, just for the public, on the
horizontal axis you have the difference in major adverse cardiovascular and cerebrovascular
events (MACCE) between CABG and PCI.

Dr Boden: Right.

Dr Serruys: We had a prespecified margin of noninferiority, which is the blue zone there, and
clearly the average difference was 5.5%. This is in the blue zone, but you have to incorporate
the 95% confidence interval, and that brings you to a value of 8.3. We crossed the margin of
noninferiority and thus the criteria for a noninferiority comparison were not met in this trial.
Thats technically the statistical statement that you have to include.

Dr Boden: Id like to ask you, Friedrich, your interpretation of the primary endpoint because
obviously SYNTAX is being discussed already as a trial that may be viewed positively by both
interventional cardiologists as well as cardiac surgeons. So, Id like your perspective on it.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
Surgeons Perspective:
Stroke rate 2.2% for CABG vs 0.6% for
PCI (P = 0.003)
Time to procedure longer for CABG
Only 30% CABG patients on
preprocedure antiplatelet therapy vs
almost all PCI on dual antiplatelet
therapy
Results for both PCI and CABG better
than expected for such complex
patients

Slide 13

Dr Mohr: I think the primary endpoint is the main thing we have to look at first, and everything
else comes thereafter. From this primary endpoint I think the message is clear: PCI is inferior
to CABG. I think one has to also look closely at how and when the MACCE occur, and we of
course have not had a real chance to get into detail. After one year, I would have expected a
higher cardiac mortality rate post-CABG instead of post-PCI. If you look in detail at these data,
especially post-procedural, death is higher in PCI than in surgery, and the problem for the
CABG patient is the stroke rate. The stroke rate is 0.6% compared with 2.2% in these
randomized cohorts, and there may be several reasons for it. The wait-time for the CABG
procedure was longer, sometimes in the UK up to one year. Also only 30% of the CABG
patients had preoperative antiplatelet therapy whereas all PCI patients had clopidogrel plus
aspirin. In addition postoperative atrial fibrillation may have played a role.

I think it will be very interesting to see what happens during the next years in terms of survival.
So, I was very surprised about the surgery result and even if you look later on in the registry
data these are excellent surgical results. But I agree that the PCI results are also very good.

Dr Boden: What percentage of patients in the CABG surgery arm had one or two arterial
grafts?

Dr Mohr: Actually, we had designed the trial with the recommendation that we would have
liked to have if possible complete revascularization in patients younger than 75. That did not
happen. We then recommended bilateral mammary arteries on the left side, and we can look
at the percentages. I think in the randomized arm the complete arterial revascularization is





This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
18.9%. Did I recall that correctly?

Dr Boden: Yes.

Dr Mohr: And the complete revascularization, arterial revascularization including radial
arteries, etc, was 21% or 22%.

Dr Boden: Now, Friedrich, I think most of us who were awaiting the results of this study would
have been willing to bet that the noninferiority would have been demonstrated at one year
because with a relatively short follow-up it would seem that the best opportunity for
demonstrating noninferiority would have been at the one-year mark. My intuition -- based on
the previously published trials -- would be that as we get deeper into follow-up, three to five
years, that the curves will continue to diverge more in favor of bypass surgery. Can you
perhaps discuss with us whether you feel that this will likely be the case? Also, now that youve
already unblinded the trial at one year, will that complicate follow-up in any respect from your
perspective?

Dr Mohr: Hopefully not. We plan for three- and five-year follow-up, and maybe well have a
chance to look in between. I think the financial background is there, and we just discussed
when we looked at the registry data where we only monitored 20% of the registry patients, that
we should find additional money to monitor all registry patients to get even more information. I
think one can discuss the divergence of the curves, but it is speculation right now. I would
expect that the cerebrovascular accident (CVA) rate from this year onward wont be that much
different, and it will have less impact on the MACCE rate than it had after one year. We need
to look now at repeat angina because patients who suffer from angina and have repeat
symptoms, thats why they get repeat revascularization.

Dr Boden: Indeed.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
PCI vs CABG: Gap Narrowing
BARI/CABRI: Difference between PCI and
CABG ~ 34%
ARTS: Reduced to ~ 14%
SYNTAX: More complex patients ~ 5.5%
difference
SYNTAX score:
Score < 22, no difference PCI vs CABG
Score 22 - 33, slight advantage for CABG
Score > 33, surgical candidate

Slide 14

Dr Serruys: If I may put this in a slightly different perspective, for me weve had three-decades
of trials comparing PCI vs surgery. You will remember that in BARI/CABRI (Bypass
Angioplasty Revascularization Investigation/Coronary Angioplasty vs Bypass
Revascularization Investigation) we had a gap of 34%, and in ARTS we reduced that to 14%
with easy patients, two-vessel disease, one-third two-vessel disease. Now we have really
taken the top of the iceberg: the main stem, and the three-vessel, and the main stem plus, and
I am very impressed. I mean its interesting that you have the 5.5% difference. Thats
absolutely remarkable.

Dr Boden: Its remarkable, the gap.

Dr Serruys: This means that we are making progress. The second comment that I would
make is that the SYNTAX score is very essential because it will allow you to modulate and to
describe your patient. We already know that if you divide the randomized population and you
take the patient with a low score of <22, the two MACCE curves are superimposed. They get
slightly separated between 22 and 33, and beyond 33, I will personally send the patient to
surgery.

Dr Boden: Right.

Dr Serruys: So, I think that there will be more ways through the continuous assessment with
the SYNTAX score to see which patient would benefit from one or the other therapies.






This is a transcript of an online program, which may be found at:
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PCI vs CABG in Multivessel Disease
Dr Boden: I agree. I think this study, for all of the reasons weve discussed already I think will
set a new standard in terms of how patients are screened and enrolled using the SYNTAX
score as a means to really identify patients who are appropriate candidates for either
approach. I want to focus just for a moment if I could, Patrick, and come back to you about
some of the important subsets within SYNTAX because you alluded to the fact a little earlier
that, historically, left main and three-vessel disease have been within the province of the
cardiac surgeon. Of course, recently we have seen some studies in some of the Korean
registry observations in left main stem stenting. How did the subset with left main disease in
SYNTAX fare?.

Dr Serruys: Well see that on the next slide. Before showing the slide I have to emphasize that
the noninferiority test is of course on the global population. So, on the following slide you will
not see any more P values because basically what you are providing to the public is
observational data, which can generate hypotheses. Thats another story.

12-month Subgroup MACCE Rates
8.5
13.2
15.8
7.1
7.5
19.8
19.3 19.2
13.7
14.4
15.4
11.5
0
5
10
15
20
25
All LM
N = 705
LM+1 VD
N = 138
LM isolated
N = 91
LM+2 VD
N = 218
LM+3 VD
N = 258
P
a
t
i
e
n
t
s

(
%
)
3 VD (all)
N = 1095
CABG TAXUS
Serruys P, et al. ESC 2008.

Slide 15

This slide is interesting because if you take the two columns at the left-hand side, thats the
global group of left main, 705 patients with left main. In blue you have the MACCE outcome of
the surgeon, 13.7% and in yellow the outcome of PCI, 15.8%. Thats for the entire cohort of the
patients with main stem, and I think it came as a surprise. I think its not wrong to say that main
stem has been for many reasons a kind of taboo in the field of interventional cardiology. That
certainly is going to progress the field. Then there are two groups. 91 patients with isolated
main stem where PCI is doing very well, 7.1% vs 8.5%. Then the next group is also interesting,
left main with one vessel. This is not a small cohort. There are 138 patients. You see in the





This is a transcript of an online program, which may be found at:
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PCI vs CABG in Multivessel Disease
small numbers the score of the surgeon, 13.2% and the score of the PCI, 7.5%. Then, you fall
back in the main stem with two- and three-vessel disease and then the superiority of surgery
emerges again in terms of revascularization for the three-vessel disease. So, I think thats an
important message, but again as you can see there is no P value on this slide because we are
below the global test for noninferiority.

Dr Boden: Right. Im wondering if we might, Friedrich, talk for a brief moment about the
registry and if we could just have your thoughts. This is the slide on the diabetics.

Outcome According to Diabetic Status
Diabetes (medical treatment)
N = 452
Nondiabetic
N = 1348
10.3
14.2
10.1
26.0
0
5
10
15
20
25
30
35
TAXUS CABG
Death/CVA/MI MACCE
Death/CVA/MI MACCE
6.8
11.8
6.8
15.1
0
5
10
15
20
25
30
35
P = 0.96 P = 0.0025
P = 0.08 P = 0.97
Death/CVA/MI MACCE
Serruys P, et al. ESC 2008.

Slide 16

Dr Serruys: Yes, I think thats the last slide from the randomized arm. Again, I think what is
somewhat surprising for both parties, the surgeon and the interventional cardiologist, is that in
the cohort of diabetics, which is not small, 452, again in terms of irreversible hard endpoints,
death, stroke, MI, we are on the same level of 10.3%, 10.1%. In the nondiabetic, its a little bit
low, 6.8% for both, but you see clearly that in the diabetic we have an issue of repeat
revascularization, which creates again this gap in MACCE in the diabetic, 14.2% vs 26%, while
the gap for the nondiabetic patients is rather small.

Dr Boden: Let me ask you to that point with the increased rate of revascularization, is there
any reason to believe that any of the other drug-eluting stents would behave differently in the
diabetic than the TAXUS stent?

Dr Mohr: That has been a debate for a long time. At a certain point it was suggested that the
placitaxel was acting on two pathways in the insulin-dependent diabetic patients. I think the





This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
evidence is not there because we never did the proper trials to prove the point. But Im sure
that in the near future people will concentrate on this very important subset of patients.

Dr Boden: Thank you. Perhaps in the time that remains we could maybe spend a few
moments, Friedrich, discussing the registry results and how you believe that these add value
to what we have learned from this trial.

12 mo follow-up
N = 191 (99.5%)
Patient Disposition: PCI registry
Lost to follow-up (N=1)
Withdrew consent 1
Medical treatment 4
CABG 1
Per-protocol
N = 192 (100%)
ITT enrolled
N = 198
Mohr F, et al. ESC 2008.

Slide 17

Dr Mohr: Yeah, I think it is very important also to reflect from the very beginning that we knew
from a 2004 website review if you looked at all three vessels that there was already a practice
of one third being treated by PCI, although there was no clinical evidence [to support this], and
two thirds were treated by surgery. We all agreed that there would be a cohort of patients who
would be too complicated for PCI and thats why the registries were so important.

We also recognized that there were some patients like those I am showing who were too sick
for one or other reason for CABG and you would do a kind of palliative PCI for these patients.
It was also important to see how often that happens and what the results are of these trials. I
will briefly walk you through that. This is giving you the numbers of the 198 patients of those
who have been so-called inoperable and they were placed into the PCI registry.






This is a transcript of an online program, which may be found at:
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PCI vs CABG in Multivessel Disease
ITT enrolled
N = 1077
12 mo follow-up
N = 633 (98.2%)
Patient Disposition: CABG Registry
Lost to follow-up (n = 10)
Withdrew consent (n = 1)
Randomly assigned to 5y follow-up
N = 649
No treatment 3
Medical treatment 2
Per-protocol
N = 644 (100%)
Mohr F, et al. ESC 2008.

Slide 18

Those are the patients who were defined by the heart team, both interventional cardiologist
and cardiac surgeon, as untreatable by PCI. From the very beginning they are classified as
surgical patients. So, there is a common decision. These are surgical patients and maybe
should remain surgical patients. You can see we enrolled more than 1000 patients, and by
random assignment 649 patients were assigned to follow up.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
Reasons for Registry Allocation
PCI registry - CABG ineligible due to:
Comorbidities (70.7%)
No graft material (9.1%)
Small or poor quality of distal vessel (1.5%)
Patient refused CABG (5.6%)
Other (13.1%)
CABG registry - PCI ineligible due to:
Complex anatomy (70.9%)
Untreatable CTO (22.0%)
Unable to take antiplatelet medications (0.9%)
Patient refused PCI (0.5%)
Other (5.7%)
Mohr F, et al. ESC 2008.

Slide 19

You see here the reasons for the PCI registry was almost always the comorbidities, and
sometimes patients who hadnt any graft material available. These were the two major factors
for the PCI registry. If you look at the CABG registry, it was as expected the very complex
anatomy and the presence of total occlusions.






This is a transcript of an online program, which may be found at:
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PCI vs CABG in Multivessel Disease
Patient Characteristics
PCI RCT vs Registry
TAXUS RCT
N = 903
PCI reg
N = 192
Age, mean SD (y) 65.2 9.7 71.2 10
Male, % 76.4 70.3
SYNTAX score 28.4 11.5 31.6 12.3
Diabetes, % 28.2 35.4
Hyperlipidemia, % 78.7 67.5
Current smoker, % 18.5 11.2
Prior MI, % 31.9 40.4
Unstable angina, % 28.9 38.0
Add. EuroSCORE, mean SD 3.8 2.6 5.8 3.1
Total Parsonnet score, mean SD 8.5 7.0 14.4 9.5
For descriptive purposes only; no statistical comparisons done.
Mohr F, et al. ESC 2008.

Slide 20

If you compare both groups, PCI randomized and registry cohorts, you can just say the
patients in the PCI registry compared with the randomized are older and sicker, which is also
depicted by both scores. The SYNTAX score was a little higher.






This is a transcript of an online program, which may be found at:
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PCI vs CABG in Multivessel Disease
Procedural Characteristics
Notable Differences: PCI RCT + Registry
TAXUS RCT
*
N = 903
PCI reg
N = 192
Staged procedure, % 14.1 13.0
Bi/trifurcation lesions treated, % 24.8 64.4
Lesions treated, mean SD 3.6 1.6 2.5 1.3
Stents implanted, mean SD 4.6 2.3 3.1 1.8
Total length implanted, mm 86.1 47.9 58.5 41.2
Range, mm 8.0-324.0 8.0-252.0
Long stenting (> 100 mm), % 33.2 12.2
For descriptive purposes only; no statistical comparisons done.
Mohr F, et al. ESC 2008.

Slide 21

If you compare you can see the treatment in the performance showed that obviously in the PCI
registry fewer lesions were treated. They focused on the culprit lesions more or less, and fewer
stents were implanted despite the complex disease, which may have an impact on outcome.






This is a transcript of an online program, which may be found at:
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PCI vs CABG in Multivessel Disease
CABG RCT
N = 897
CABG reg
N = 644
Age, mean SD (y) 65.0 9.8 65.7 9.4
Male, % 78.9 80.7
SYNTAX score, mean SD 29.1 11.4 37.8 13.3
Diabetes, % 28.5 29.7
Hypertension, % 77.0 73.5
Hyperlipidemia, % 77.2 76.4
Current smoker, % 22.0 21.9
Prior MI, % 33.8 33.5
Unstable angina, % 28.0 21.6
Add. EuroSCORE, mean SD 3.8 4.4 3.9 2.7
Total Parsonnet score, mean SD 8.4 6.8 9.0 7.1
Patient Characteristics
CABG RCT vs Registry
For descriptive purposes only; no statistical comparisons done
Mohr F, et al. ESC 2008.

Slide 22

Comparing the CABG randomized cohort to the CABG registry cohort, as expected the major
difference and maybe the only difference is the complexity of the disease, which is expressed
in the SYNTAX score of 29 compared with about 38.






This is a transcript of an online program, which may be found at:
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PCI vs CABG in Multivessel Disease
Patients (%)
7.3
0
4.2
10.5
20.4
Per-protocol population
12.0
0
5 15 20 10
All death
CVA
MI
Death/CVA/MI
Revascularization
Total MACCE
25
Inhospital MACCE
Mohr F, et al. ESC 2008.
12-month MACCE Rates
PCI Registry (N = 192)

Slide 23

If we look at the MACCE rates of the PCI registry, you can see there is a respectable outcome.
So, this is really a viable option for these patients, 7.3% death rate at 12 months and a total
MACCE rate of 20.4%. And of course repeat revascularization is relatively high.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
0 12
C
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m
u
l
a
t
i
v
e

e
v
e
n
t

r
a
t
e

(
%
)
Event rate 1.5 SE
10
20
30
0
Months since allocation
6
Per-protocol population
Overall MACCE to 12 Months
PCI Registry
20.4%
Mohr F, et al. ESC 2008.

Slide 24

So, this shows you the MACCE rate, which is from the very beginning growing step by step
through the whole twelve months.







This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
3.4
0.6
1.2
1.6
0.3
0
2
4
6
8
Death Revasc MI MACCE Stroke
P
a
t
i
e
n
t
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(
%
)
30-Day MACCE Post-Procedure
CABG Registry (N = 644)
Mohr F, et al. ESC 2008.

Slide 25

What is interesting, of course, and what we as surgeons always want to know at the very
beginning is the procedural outcome of surgery if we operate on these patients? This was quite
surprising. If you look at the 30-day mortality. and I will come to the 12 months, we had
extremely good results, even better results than in the randomized cohort. So, the procedural
mortality was 0.6% and the stroke rate was lower.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
2.5
2.2
2.5
6.6
3.0
Per-protocol population
All death
CVA
MI
Death/CVA/MI
Revascularization
Total MACCE
8.8
Inhospital MACCE
0 5 15 20 10 25
Patients (%)
Mohr F, et al. ESC 2008.
12-Month MACCE Rates
CABG Registry (N = 644)

Slide 26

The MACCE rate at the very end at 12 months, as you can see here, sums up to 8.8%.
Remember, we had 12.1% in the SYNTAX cohort, in the randomized part. We really dont
have a true answer to that. You see the all-cause mortality at 12 months in the registry arm is
2.5% and so this is a very remarkable surgical result; I have not seen one this good in any of
the studies yet in the surgical literature at least none of the multicenter trials.

Dr Boden: I think thats a very impressive finding. So, in the moments that remain I want to
just ask each of you, first beginning with you, Friedrich, the noninferiority standard at one year
was not met in this trial. Is it your opinion that we will see more bypass surgery in patients with
left main and three-vessel disease or not? How will this trial be incorporated into clinical
practice in your opinion?






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
SYNTAX Surgeons Conclusions:
The primary endpoint (12-months MACCE) in this
noninferiority trial for PCI was not met
PCI continues to improve as do surgical techniques
In this trial, the heart team concluded that CABG
remains the only treatment option for at least 1/3
of the patients screened
In patients who are not candidates for PCI, surgical
results are excellent
In patients who are not candidates for CABG, PCI is
a viable option
Mohr F, et al. ESC 2008.

Slide 27

Dr Mohr: Ill just give you my personal opinion. I have learned a lot during this trial to
understand both treatments better. It was very enlightening for me to see how well
interventionalist cardiologists also perform in simple lesions. I think this is something that is a
benefit of the trial, that we will look more closely at the patient and the disease of the patient
and then make our decisions. Its not only the complexity of the disease; it also will be the age
of the patient. If its a younger patient, we may be more likely to decide to go for surgery as a
permanent solution. If its an older patient, it may be different. Right now from the results there
is an answer. We expect the next three years' results will yield a better answer. I personally
was expecting that noninferiority would be met at twelve months, and I am very positively
surprised by the outcome. Now, in the interest of the surgeons I think the message is, like
Patrick and me, we talk to each other, we hardly dispute each other, and it is I think a gain for
the patient that we sit together, the surgeon and cardiologist, and decide what can I do, what
can you do, and think about what will yield the best result for the complex patient.

Dr Boden: So, clearly at one year SYNTAX is very good news for the cardiac surgeon, but,
Patrick, also very good news for the interventional cardiologist.






This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease
SYNTAX Interventionalists Conclusions:
Comparable overall safety outcomes (death, CVA,
MI,) in CABG and PCI patients at 12 months (7.7%
vs 7.6%)
Per protocol rates of symptomatic graft occlusion
and stent thrombosis were similar
Significantly higher rate of revascularization in the
PCI group (13.7% vs 5.9%), and a significantly
higher rate of CVA in the CABG group (2.2% vs
0.6%)
Overall MACCE higher in the PCI group (17.8% vs
12.1%) due to an excess of redo revascularization
vs CABG
The SYNTAX score will help stratify patients for the
appropriate revascularization option
Serruys P, et al. ESC 2008.

Slide 28

Dr Serruys: Its also very good news because basically we are addressing together with the
surgeon the most difficult patient in the field of CAD, the main stem and the three-vessel
disease. Thats the first point. I think that clearly you have a statistical test, which is applicable
to main stem and three-vessel disease. But I think what we have attempted from the very
beginning of this trial is to dissect the three-vessel disease. You are three-vessel disease, and
you go to surgery. Im a three-vessel disease, and I go to PCI. Thats the phenomenon we tried
to understand.

We spent almost one year elaborating the SYNTAX score, which is much more relevant for the
interventional cardiologist than for the surgeon. They are immune from the SYNTAX score, an
easy case or a difficult one; it doesnt make any difference for them. For us it makes a big
difference. So, my expectation in the future is that first I think that there will be a slow
divergence of the curve. That is something I have seen in every trial with time, not necessarily
in mortality, but at least in revascularization. We have seen that in ARTS2 where you have the
phenomenon of erosion by late stent thrombosis and this kind of thing. But I think the important
point that we have to do, and it is a heavy task for the future, is to educate the public and our
colleagues to use the SYNTAX score and to judge together with the surgeon if this is a patient
where the chances are equal. This is in the randomized trial not looking at the patient that was
clearly too complicated for the interventional cardiologist. So, I think we are going to dissect
the randomized arm with the SYNTAX score, and we already have made the assessment that
by consensus more than one third of the patients will go to surgery. So, in general its good
news for both of us. I mean I think we are very pleased to have a better understanding of CAD
and revascularization.





This is a transcript of an online program, which may be found at:
http://www.theheart.org/article/883817.do

PCI vs CABG in Multivessel Disease

Dr Boden: Again, just to further this discussion and to conclude it, I think its also very good
news for our patients. I think what it tells us is that we really have two excellent
revascularization options, and I think using the SYNTAX score will really reshape the way that
we approach complex CAD in the stable CAD patient.

Dr Mohr: I hope so.

Dr Boden: I want to once again just complement both of you on the phenomenal contribution
youve made to advance the care of patients with complex CAD. I think we anxiously await the
publication so that we can digest fully the results of this important study. Again, I want to thank
Professors Mohr and Serruys for joining us on Spotlight today. Thank you.