1. Final Five-Year Follow-up of the SYNTAX Trial: Optimal Revascularization Strategy in Patients With Three-Vessel Disease and/or Left Main Disease
Patrick W. Serruys, MD, PhD
Thorax Centre, Erasmus MC
On behalf of the SYNTAX investigators
9:06-16 a.m., Oct 22, 2012
Hall A, Coronary theater
Conflicts of Interest: None 1

2. I, P. W. Serruys, DO NOT have a financial interest/arrangement or affiliation with one or more organizations that could be perceived as a real or apparent conflict of interest in the context of the subject of this presentation.

3. Study Design & Patient Disposition
62 EU Sites +
23 US Sites
De novo 3VD and/or LM (isolated, +1,2,3 VD)
Heart Team (Surgeon & Interventional Cardiologist) Review Randomized if suitable for either CABG or PCI or Enrolled in nested registry if not equally suitable
CABG Reg.
n=649*
CABG RCT
n=897
PCI RCT
n=903
PCI Registry
n=198
Enrolled
CABG
n=644**
From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc Exhibit 5
SYNTAX 5-Year Report_Randomized_15JUN12.doc Exhibit 4 (evaluable for 5-year MACCE)
SYNTAX 5-Year Report_Registry_22JUN12.doc Exhibits 4 and 8
CABG
849 (94.6%)
PCI
891 (98.7%)
PCI
n=192**
Primary Endpoint 1 Year Follow-up
CABG
610 (94.7%)
CABG
805 (89.7%)
Completed Study
5 Year Follow-up
PCI
871 (96.5%)
PCI
188 (97.9%)
*N=649 followed for 5 years, N=1077 enrolled, **CABG N=644, PCI N=192 treated per protocol. PCI performed with TAXUS Express

4. Patient Characteristics
CABG RCT N=897
PCI RCT N=903
P value
CABG Registry N=644
PCI Registry N=192
Age* (y)
65.0±9.8
65.2±9.7
0.55
65.7±9.4
71.2±10.4
Male, %
78.9
76.4
0.20
80.7
70.3
Diabetes*†, %
24.6
25.6
0.64
26.4
30.2
Additive euroSCORE*
3.8±2.7
3.8±2.6
0.78
3.9±2.7
5.8±3.1
Total Parsonnet score*
8.4±6.8
8.5±7.0
0.76
9.0±7.1
14.4±9.5
Total SYNTAX Score
29.1±11.4
28.4±11.5
0.19
37.8±13.3
31.6±12.3
Mean # of lesions
4.4±1.8
4.3±1.8
0.44
4.6±1.7
4.5±1.8
3VD only, %
66.3
65.4
0.70
59.7
66.7
Left main, any, %
33.7
34.6
40.3
33.3
Total occlusion, %
22.2
24.2
0.33
56.4
36.5
Complete revasc, %
63.2
56.7
0.005
74.7
From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc
Exhibit 6,7,9
SYNTAX CSR Registry Unblinded_2008Oct10.doc Exhibits 5, 6, 8, 24, 25, 27
Values are mean±SD or %. Core laboratory reported unless *Site-reported †Medically treated 4

5. All-Cause Death to 5 Years
TAXUS (N=903)
CABG (N=897)
Before 1 year*
3.5% vs 4.4%
P=0.37
1-2 years*
1.5% vs 1.9%
P=0.53
2-3 years*
1.9% vs 2.6%
P=0.32
3-4 years*
2.2% vs 3.2%
P=0.22
4-5 years*
3.1% vs 2.3%
P=0.34 25 50
P=0.10
Cumulative Event Rate (%)
1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1
2-Year_Randomized_ doc Exhibit 2 (binary interval rate)
SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate)
SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box)
13.9%
11.4% 12 60 24 36 48
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
ITT population 5

6. Cardiac Death to 5 Years TAXUS (N=903) CABG (N=897) 25 50 P=0.003
Before 1 year*
2.1% vs 3.7%
P=0.0503
1-2 years*
0.6% vs 0.8%
P=0.62
2-3 years*
0.9% vs 1.6%
P=0.22
3-4 years*
0.8% vs 1.6%
P=0.13
4-5 years*
1.1% vs 1.4%
P=0.56 25 50
P=0.003
Cumulative Event Rate (%)
1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1
2-Year_Randomized_ doc Exhibit 2 (binary interval rate)
SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate)
SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box)
9.0%
5.3% 12 60 24 36 48
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
ITT population 6

7. Myocardial Infarction to 5 Years
TAXUS (N=903)
CABG (N=897)
Before 1 year*
3.3% vs 4.8%
P=0.11
1-2 years*
0.1% vs 1.2%
P=0.008
2-3 years*
0.3% vs 1.2%
P=0.03
3-4 years*
0.3% vs 1.5%
P=0.01
4-5 years*
0% vs 1.2%
P=0.004 25 50
P<0.001
Cumulative Event Rate (%)
1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1
2-Year_Randomized_ doc Exhibit 2 (binary interval rate)
SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate)
SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box)
9.7%
3.8% 12 60 24 36 48
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
ITT population 7

8. CVA to 5 Years TAXUS (N=903) CABG (N=897) 25 50 P=0.09
Before 1 year*
2.2% vs 0.6%
P=0.003
1-2 years*
0.6% vs 0.7%
P=0.82
2-3 years*
0.5% vs 0.6%
P=1.00
3-4 years*
0.4% vs 0.2%
P=0.68
3-4 years*
0% vs 0.1%
P=1.00 25 50
P=0.09
Cumulative Event Rate (%)
1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1
2-Year_Randomized_ doc Exhibit 2 (binary interval rate)
SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate)
SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box)
3.7%
2.4% 12 60 24 36 48
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
ITT population 8

9. All-Cause Death/CVA/MI to 5 Years
TAXUS (N=903)
CABG (N=897)
Before 1 year*
7.7% vs 7.6%
P=0.98
1-2 years*
2.2% vs 3.5%
P=0.11
2-3 years*
2.5% vs 3.8%
P=0.14
3-4 years*
2.7% vs 4.6%
P=0.051
4-5 years*
3.1% vs 3.1%
P=0.98 25 50
P=0.03
Cumulative Event Rate (%)
20.8%
1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1
2-Year_Randomized_ doc Exhibit 2 (binary interval rate)
SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate)
SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box)
16.7% 12 60 24 36 48
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
ITT population 9

10. Repeat Revascularization to 5 Years
TAXUS (N=903)
CABG (N=897)
Before 1 year*
5.9% vs 13.5%
P<0.001
1-2 years*
3.7% vs 5.6%
P=0.06
2-3 years*
2.5% vs 3.4%
P=0.33
3-4 years*
1.6% vs 4.2%
P=0.002
4-5 years*
1.9% vs 4.3%
P=0.008 25 50
P<0.001
25.9%
Cumulative Event Rate (%)
1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1
2-Year_Randomized_ doc Exhibit 2 (binary interval rate)
SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate)
SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box)
13.7% 12 60 24 36 48
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
ITT population 10

11. MACCE to 5 Years TAXUS (N=903) CABG (N=897) 25 50 P<0.001 37.3%
Before 1 year*
12.4% vs 17.8%
P=0.002
1-2 years*
5.7% vs 8.3%
P=0.03
2-3 years*
4.8% vs 6.7%
P=0.10
3-4 years*
4.2% vs 7.9%
P=0.002
4-5 years*
5.0% vs 6.3%
P=0.27 25 50
P<0.001
37.3%
Cumulative Event Rate (%)
26.9%
1 yr data From SYNTAX_CSR_randomized_Unblinded_2008Oct10.doc exhibit 1
2-Year_Randomized_ doc Exhibit 2 (binary interval rate)
SYNTAX 3-Year Report_Randomized_12JUL10.doc Exhibit 2 (binary interval rate)
SYNTAX 4-Year Report_Randomized_15JUN11.doc exhibits 1 (KM rate on right sidea) and exhibit 2 (binary interval rate in white box) 12 60 24 36 48
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value;*Binary rates
ITT population 11

12. Per Protocol Graft Occlusion or Stent Thrombosis to 5 Years (Per Patient Binary Rates)
PCI
CABG
Patients (%)
(3/870)
(3/868)
(12/854)
(2/812)
(6/790)
(3/764)
(3/729)
(32/581)
SYNTAX 5-Year Report_Randomized_22JUN12.doc Exhibit 9
(2/896)
(18/893)
(8/874)
(5/850)
(4/830)
(7/803)
(5/768)
(47/708)
Acute
≤1d
Subacute
2-30d
Late
31-365d
Very Late
Total
5 year d d d d
Days Postprocedure
Per protocol GO and ST: clinical presentation of ACS with angiographically confirmed occlusion within/adjacent to a previously successfully treated lesion/graft during follow-up and/or Q-wave MI in the treated vessel territory within 30 d of the index procedure. Numbers are per patient, 1PCI patient had an ST 1d and 6d post-procedure; therefore, counted in the ≤1d and 2-30d intervals but only once in the total. 12

13. MACCE to 5 Years by SYNTAX Score Tercile Low Scores (0-22)
TAXUS (N=299)
CABG (N=275)
CABG
PCI
P value
Death
10.1%
8.9%
0.64
CVA
4.0%
1.8%
0.11 MI
4.2%
7.8%
Death, CVA or MI
14.9%
16.1%
0.81
Revasc.
16.9%
23.0%
0.06
Overall 50
32.1%
P=0.43
Cumulative Event Rate (%) 25
28.6%
SYNTAX 5-Year Report_Randomized_15JUN12.doc exhibit 53 12 24 36 48 60
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value
Core lab-reported Data; ITT population

14. MACCE to 5 Years by SYNTAX Score Tercile Intermediate Scores (23-32)
TAXUS (N=310)
CABG (N=300)
CABG
PCI
P value
Death
12.7%
13.8%
0.68
CVA
3.6%
2.0%
0.25 MI
11.2%
<0.001
Death, CVA or MI
18.0%
20.7%
0.42
Revasc.
24.1%
Overall 50
36.0%
P=0.008
Cumulative Event Rate (%) 25
SYNTAX 5-Year Report_Randomized_15JUN12.doc exhibit 55
25.8% 12 24 36 48 60
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value
Core lab-reported Data; ITT population

15. MACCE to 5 Years by SYNTAX Score Tercile High Scores (33)
TAXUS (N=290)
CABG (N=315)
CABG
PCI
P value
Death
11.4%
19.2%
0.005
CVA
3.7%
3.5%
0.80 MI
3.9%
10.1%
0.004
Death, CVA or MI
17.1%
26.1%
0.007
Revasc.
12.1%
30.9%
<0.001
Overall 50
P<0.001
44.0%
Cumulative Event Rate (%) 25
26.8%
SYNTAX 5-Year Report_Randomized_15JUN12.doc exhibit 57 12 24 36 48 60
Months Since Allocation
Cumulative KM Event Rate ± 1.5 SE; log-rank P value
Core lab-reported Data; ITT population

16. The 5-year Outcomes of the SYNTAX Trial CABG Registry and PCI Registry

17. MACCE to 5 Years SYNTAX CABG Registry
CABG Registry (n=644)
SYNTAX Score: 37.8±13.3 Additive EuroSCORE: 3.9±2.7 Complete revascularization: 74.7%
Patients (%)
23.2
SYNTAX 5-Year Report_Registry_15JUN12.doc Exhibit 5 for graph and SYNTAX CSR Registry_Unblinded_2008Oct10.doc Exhibits 24, 25, 27 for text box
All Death
Cardiac Death MI
CVA
Revasc.
MACCE 17

18. MACCE to 5 Years SYNTAX PCI Registry
PCI Registry (n=192)
SYNTAX Score: 31.6 ± 12.3 Additive EuroSCORE: 5.8 ± 3.1 Complete revascularization: 36.5%
49.2
Patients (%)
SYNTAX 5-Year Report_Registry_15JUN12.doc exhibit 1 for graph and SYNTAX CSR Registry_Unblinded_2008Oct10.doc Exhibits 5,6, 8 for text box
All Death
Cardiac Death MI
CVA
Revasc.
MACCE 18

19. MACCE to 5 Years Interpreting Results Based on SYNTAX Score
PCI only 7%
CABG only
PCI or CABG
71%
22%
Get totals for # of patients from:
SYNTAX 5-Year Report_Registry_22JUN12.doc Exhibits 1 and 5 for PCI and CABG Registries
SYNTAX 5-Year Report_Randomized_15JUN12.doc exhibits 53, 55, and 57 for SYNTAX Score groups
Add number of patients in registries and SYNTAX Score groups to get total # of patients in trial
Calculate percentages by hand as follows:
For CABG only: Number of patients in (CABG Registry)+(23 to 32 group)+(33+ group) divided by total number of patients in trial (numerator should also be the # of patients in blue wedges in pie chart)
For PCI or CABG: Number of patients in (0 to 22 group) divided by total number of patients in trial
PCI Only: Number of patients in (PCI Registry) divided by total number of patients in trial.
Five-year results of the SYNTAX trial suggest that 71% of all patients are still best treated with CABG; however, for the remaining patients PCI is an alternative to surgery

20. Thank you to the SYNTAX Steering Committee and Investigators
Summary & Conclusions
The final 5-year results of the SYNTAX trial demonstrate that surgery remains the gold standard for patients with complex multivessel disease
In patients with less complex disease, PCI is an acceptable alternative treatment
Treatment decisions for an individual patient should continue to be made in consultation between the patient and the Heart Team, while considering the risks and benefits of the respective treatment options
Thank you to the SYNTAX Steering Committee and Investigators