1. SYNTAX at 2 Years: This Interventionalist’s Perspective
David J. Cohen, M.D., M.Sc.
Director of Cardiovascular Research
Saint Luke’s Mid America Heart Institute
Professor of Medicine University of Missouri-Kansas City

2. I am a practicing interventional cardiologist
DISCLOSURES
David J. Cohen, MD
Consulting Fees
Medtronic CardioVascular, Inc., Cordis, a Johnson & Johnson company
Grants/Contracted Research
Abbott Vascular, Boston Scientific Corporation, Daiichi Sankyo, Inc. and Eli Lilly and Company, Edwards Lifesciences LLC
I am a practicing interventional cardiologist
I have many friends who are cardiac surgeons (and a couple of them are actually pretty smart!)

3. SYNTAX Trial: Design
1800 patients with 3-vessel or left main CAD, considered to be suitable for both PCI and CABG by both an interventional cardiologist and CT surgeon
Randomized to PCI with TAXUS DES (n=903) or CABG (n=897)
Primary endpoint = Death, MI, Stroke, or repeat revacularization (MACCE) at 1 year
Parallel registries of patients felt to be only suitable for either PCI (n=198) or CABG (n=1077), but not both

4. 2-Year MACCE SYNTAX P<0.001 20 40 Cumulative Event Rate (%) 23.4%
Before 1 year*
12.4% vs 17.8%
P=0.002
After 1 year*
5.7% vs 8.3%
P=0.03
Cumulative Event Rate (%)
23.4%
16.3% 12 24
Months Since Allocation
Kappetein P et al. ESC 2009 4

5. All-Cause Death/CVA/MI to 2 Years
TAXUS (N=903)
CABG (N=897)
P=0.44 20 40
Before 1 year*
7.7% vs 7.6%
P=0.98
After 1 year*
2.2% vs 3.5%
P=0.11
Cumulative Event Rate (%)
1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1
2-Year_Randomized_ doc Exhibits 1&2 compare curves to Exhibit 9
10.8%
9.6% 12 24
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
ITT population 5

6. Repeat Revascularization to 2 Years
TAXUS (N=903)
CABG (N=897)
P<0.001 20 40
Before 1 year*
5.9% vs 13.5%
P<0.001
After 1 year*
3.7% vs 5.6%
P=0.06
Cumulative Event Rate (%)
17.4%
1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1
2-Year_Randomized_ doc Exhibits 1&2 compare curves to Exhibit 15
8.6% 12 24
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
ITT population 6

7. SYNTAX in Perspective:
Quality of Life
Since there is no significant difference in mortality at 2 years, the next most important outcome from a patient’s perspective is symptoms and quality of life

8. Primary QOL Endpoint: SAQ-Angina Frequency
PCI Benefit vs. OMT in COURAGE
6 6 months
3 points @ 12 months

9. Generic QOL and Utilities30 35 40 45 50 55
Baseline
1 month
6 months
12 months
P<0.001
P=0.50
P=0.07 SF -
36 Physical Component Summary 30 40 50
Baseline
1 month
6 months
12 months SF -
36 Mental Component Summary
P<0.001
P=0.23
P=0.43
0.5
0.6
0.7
0.8
0.9 1
Baseline
1 month
6 months
12 months
P<0.001
P=0.16
P=0.99 EQ -
5D Utilities (US)
PCI
CABG
Quality Adjusted Life Years
D = 0.02 (P<0.01)

10. SYNTAX in Perspective:
Subgroups

11. 2 Year Outcomes in 3VD and LM Subgroups
TAXUS
CABG
P=0.11
P<0.001
P<0.001
P=0.48
P=0.01
P=0.27
Patients, %
Patients, %
2-Year_Randomized_ doc Exhibits 19 & 21
Death/CVA/MI
Revasc
MACCE
Death/CVA/MI
Revasc
MACCE
3 Vessel Disease
n=1095
Left Main Disease
n=705
Time-to Event; Log-rank P value
ITT population

12. 2-Year MACCE: SYNTAX Score Tertiles
P<0.001
P=NS
P=NS
P = for interaction
Low (≤22)
Middle 23-32
High (≥33)
CABG
PCI

13. Cost-Effectiveness of CABG vs. PCI ($/QALY) SYNTAX Score Tertiles
Dominated
ICER
-0.047
D QALY
$6154
D Cost
Low (≤22)
Pr <$50K/QALY = 0.0%
Dominated
ICER
-0.013
D QALY
$3889
D Cost
Mid (23-32)
Pr <$50K/QALY = 0.3%
$43,000/QALY
ICER
+0.010
D QALY
$467
D Cost
High (≥33)
Pr <$50K/QALY = 49%

14. SYNTAX at 2 Years
Dirty Little Secrets
CABG results representative of current US practice
Although it’s possible that greater use of bilateral IMAs would have resulted in better outcomes, there are currently no RCT data to support this assertion
This would also require a substantial change from current standard of care
PCI results could definitely have been better
TAXUS recently shown to be inferior to Xience V for both TVR and MI outcomes
FAME suggests that better results could have been achieved with fewer stents by using physiologic guidance

15. SYNTAX at 2 Years
What have we learned?
Some patients are uniquely suited to PCI or CABG due to comorbid conditions or technical issues
Most patients with multivessel disease will have a choice
For these patients, the decision is largely based on one’s preference to either avoid bypass surgery (and the prolonged recovery period) or to avoid the need for additional procedures in the short-to-intermediate term

16. What else have we learned?
SYNTAX at 2 Years
What else have we learned?
The SYNTAX score may be a helpful tool to better inform patients and their physicians about the relative benefits of PCI and CABG– particularly in complex 3-vessel disease (where CABG is the clear winner)
If the SYNTAX results can be replicated, left main disease (especially isolated LM) may be a highly attractive subset for PCI in the future