1. Compare Trial 2 year follow-up
Peter Smits
Maasstad Ziekenhuis
Rotterdam
The Netherlands

2. Disclosures I have received a speaking fee from Abbott Vascular
Research Foundation of the Cardiology Department has received unrestricted research grants from:
Abbott Vascular
Boston Scientific
Here are my disclosures, I have received ……. the research foundation of my cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific.

3. Compare Trial The COMPARE trial is a physician initiated single center
prospective randomized trial
comparing the
Taxus Liberté ™ versus Xience V™ stent
in an all-comer / real world situation
Zie dia

4. Compare Trial Purpose of the study
To study the outcome of 2e generation drug eluting stents in a study design that reflects
everyday clinical practice
The study is patient oriented and uses only symptom driven clinical end-points
Purpose of the COMPARE trial is to study …..

5. Study Outline
The study outline was simple and straightforward. All eligible patients for PCI could be included. After guide-wire passage and pre-dilatation at the discretion of the operator, just before the stenting procedure, a operator blinded 1: 1 randomisation by a closed envelope method was performed. Patients were randomized towards a Taxus Liberte or a Xience V stent.
Clinical events were adjudicated by an independent CEC and target vessel revascularizations were analysed by an independent core lab.

6. Study Outline Inclusion criteria All patients eligible for PCI
Life expectancy of > 5 years
Exclusion criteria
No dual antiplatelet therapy for 12 months
Cardiogenic shock at presentation
Expected planned major surgery within 1 month
Participation in another trial
No informed consent
Estimated life expectancy of > 5 years

7. Patient Diagram and Follow-up
Randomized
(N=1800)
Taxus Liberté
(N=903)
XIENCE V (N=897)
Lost to f/u = 2
Lost to f/u = 1
No study stent = 6
No study stent = 4
1-Year Follow-up (N=1797; 99.8%)
Taxus Liberté
(N=902)
XIENCE V (N=895)
Lost to f/u = 2
Lost to f/u = 0
Of the 1800 pts randomized, 903 were allocated to Taxus Liberte stents and 897 pts were allocated to Xience V stents.
At 1 year follow up, only 3 patients were lost to follow up, and in the second year we lost another 2 patients for follw-up, so that at 2 year we have follow up data on 99.7 % of our patients.
2-Year Follow-up (N=1795; 99.7%)
Taxus Liberté
(N=900)
XIENCE V (N=895)
Clinical events were adjudicated by an independent CEC
Target vessel revascularizations were analysed by an independent QCA core lab. 7

8. Endpoints Primary endpoint Secondary endpoints *
All death, non fatal MI and Target Vessel Revascularization (TVR) at 12 months follow-up
Secondary endpoints *
Cardiac death, non fatal MI, ischemic driven TLR rate annually during 5 years follow-up
All death, non fatal MI, TVR at year follow-up
Incidence of definite, probable or possible stent thrombosis annually during 5 years follow-up
The primary endpoint was defined as the composite of: all death etc.
The secondary endpoints: like the composite of cardiac death etc. and the primary endpoint and the stent thrombosis were originally defined at 1, 3 and 5 year follow-up, but these have been amended to an annual reporting during the 5 years follow up period.
* amended from 1,3 and 5 years to annual time points during 5 year follow up

9. Baseline Characteristics Clinical presentation 1800 pts.
Taxus
903 pts
Xience
897 pts p
Male
72 %
69 %
0.11
Previous AMI
17.6 %
15.2 %
0.37
Previous PCI
13.6 %
13.0%
0.57
Previous CABG
5.9 %
6.7 %
0.47
Previous CVA
6.4 %
4.2 %
0.07
Peripheral artery disease
3.5 %
5.7 %
Diabetes
19 %
17.1 %
0.33
Smoking (active)
29 %
32.9 %
0.23
Hypercholesterolemia
49.9 %
53.2 %
0.24
Hypertension
49.5 %
46.5%
0.29
Family History
44.6 %
44.5 %
0.61
This slide represents the patient baseline characteristics.
The cardiovascular antecedents and risk factors were similar in both patients groups.

10. Clinical Presentation 1800 pts.
Taxus
Xience
Clinical presentation at the index procedure was similar between both groups. And in both groups approximately 60% of the patients presented with an acute coronary syndrome.
± 60% ACS
p = ns

11. Baseline Characteristics 1800 patients / 2583 lesions
Taxus
Xience p
Lesions
1294
1286 ns LM
1.6 %
0.46
LAD
37.4 %
39.9 %
RCX
25.7 %
23.2 %
RCA
33.3 %
32.9 %
Grafts
1.9 %
2.1 %
0.55
Lesion per patient
1.46
1.45
0.92
Stent length per lesion
34.0
0.97
Stent per lesion
1.57
1.67
0.07
GP 2b3a blockers
32 %
0.64
B2 / C lesions
73 %
74%
0.20
This slide represents the baseline characteristics of 2583 lesions: 1294 lesions in the Taxus group and 1286 lesions in the Xience group.
The lesions were equally distributed among the coronary arteries.
On average 1.45 lesions per patient were treated, with an average stent length per lesion of 34 mm. A trend towards more stents per lesion in the Xience group possible reflects the situation that no 32 mm Xience stent is available compared to the 32 mm Taxus stent.
Usage of GP2a3b blocers was the same in both groups.

12. Chronic renal failure 3 %
COMPARE TRIAL
AMI 25 %
Calcification 34 %
Multistenting 62 %
Ostial 19 %
Thrombus 24 %
CTO 4 %
NSTEMI 23 %
Multivessel 27 %
Saphenous graft 2 %
Bifurcation 10 %
Diabetes 18 %
Chronic renal failure 3 %
Left main 2 %
Direct stenting 34 %
“REAL WORLD”
Therefore, we can say that the COMPARE trial truly reflects a real world situation with:………

13. Summary 12 months endpoints
Taxus
Xience
Primary endpoint :
All death, MI and TVR
Cardiac death, MI and
Ischemia driven TLR
P = 0.023
P = 0.005
Def. & Prob. stent thrombosis
Myocardial infarction
This is a summary of the 12 months endpoints that were published in the Lancet paper january this year.
The primary endpoint, the lesion specific composite endpoint , thombosis and myocardialo infarction rate all were significant lower in the Xience V stent group
P = 0.002
P = 0.007
Kedhi et al. Lancet 2010; vol 375: 201-9

14. Summary 12 months endpoints
All death
Taxus
Xience
Cardiac death
P = 0.58
P = 0.81
TVR
TLR
P =
P =
Kedhi et al. Lancet 2010; vol 375: 201-9

15. SPIRIT IV TRIAL COMPARE TRIAL 12 months result Overall Overall
Everolimus
better
Paclitaxel
better
Everolimus
better
Paclitaxel
better
Overall
Overall
< 65 yr
> 65 yr
No diabetes
Diabetes
Male
Female
Female
Male
Diabetes
No diabetes
No ACS
ACS
Hypertension
No hypertension
Single vessel
Multivessel
Hypercholesterol
No hyperchol.
Restenosis
De Novo
BMI < 30
BMI > 30
Stable angina
No stable ang.
No Acute MI
Acute MI
In the subgroup analysis at 12 months a trend was observed towards better outcome with the Xience V stent in almost all subgroups, apart from the diabetic population.
The same was observed in the 12 months results of the Spirit IV trial.
1 lesions
2 or more lesions
No proximal LAD
Proximal LAD
No complex
Complex lesions
Lesion < 20 mm
Lesion ≥ 20 mm
RVD < 2.75
RVD > 2.75
RVD ≥ 2.75 mm
RVD < 2.75 mm
Lesion < 13.3
Lesion > 13.3
0.1
Bail-out
No Bail-out
0.1
1.0
10.0
0.1
1.0
10.0

16. Dual anti platelet therapyns ns ns
P = 0.02
Now I come to the 2 year follow-up data.
According daily clinical practice DAPT was stopped in vast majority of patients after 1 year, and at 2 year Taxus stent group 15.2% and in the Xience group 11.4 % were on DAPT, which was significant different. *
15.2 %
11.4 %

17. Primary Endpoint Result @ 2 yr MACE (all death, non-fatal MI and TVR)
13.7 %
Taxus
Xience
Δ 4.7 %
9.1 %
Δ 2.9 %
9.0 %
6.2 %
P = (log-rank test)
RR = 0.66 ( )
This is the result of the primary end-point at 2 year: the composite of all death, non fatal MI and TVR.
At 12 months follow up, the significant difference of 2.9% in MACE increased to 4.7 % at 2 years follow-up.
At two year follow-up, the MACE rate is 13.7 % in Taxus versus 9.0% in Xience group, which is highly statistic significant different according the log rank test, with a rate ratio of 0.66 and 95% Confidence Interval of 0.50 to 0.86
This absolute difference of 4.7% results in a 33 % relative risk reduction.
# Patients at Risk
Taxus
Xience

18. Secondary Endpoint Result @ 2 yr MACE (cardiac death, non-fatal MI and TLR)
Taxus
Xience
11.4 %
8.2 %
Δ 4.0 %
Δ 3.3 %
7.4 %
4.9 %
This is the result of the first secondary endpoint: the composite of cardiac death, non-fatal MI and ischemic driven target lesion revascularization.
Again, the difference in event rate between both stent groups gradually increased over time with an significant difference of 3.3% at 1 year, which increased to 4.0 % at 2 year, with a 11.4% MACE rate in the Taxus group compared to 7.4 % in the Xience group, which is highly significant different with a p value of and rate ratio of 0.65 with confidence interval below 1.0.
P = (log-rank test)
RR = 0.65 ( )
# Patients At Risk:
Taxus
Xience

19. First Stent Thrombosis @ 2 yr (Definite / Probable according to ARC)
Taxus
Xience
3.9 %
Δ 3.0 %
2.6 %
P < (log-rank test)
RR = 0.23 ( )
Definite & probable stent thrombosis rate according to the ARC definitions which was already highly significant different between both groups, with a 2.6% in the Taxus group versus 0.7% in the Xience group at 12 months, increased to an absolute difference of 3.0 % at 2 years follow-up. Of interest is the low stent thrombosis rate of less then 1% in the Xience group in this all-comer polulation and with only 11% of the patients on DAPT.
Δ 1.9 %
0.9 %
0.7 %

20. Early, Late and Very Late stent Thrombosis (Definite / Probable according to ARC)
Early ST
92 % pts on DAPT
Late ST
70 % pts on DAPT
Very Late ST
13 % pts on DAPT
p = 0.002
RR 0.13 ( )
p = 0.13
RR 0.38 ( )
p = 0.013
RR 0.23 ( )
Taxus
Xience
This landmark presentation represents the differences in stent thrombosis rate during the early, late and very late phase.
There is a significant difference in the early phase, a trend in the late phase and a significant difference in the very late phase with only 13% on average on DAPT, all in favour of the Xience V stent.
1.7 %
1.5 %
0.9 %
0.2 %
0.3 %
0.3 % 15 30 30 60
120
180
240
300
360
360
420
480
540
600
660
720
Days

21. First Definite Stent Thrombosis @ 2 yr (Definite according to ARC)
Taxus
Xience
P < (log-rank test)
RR = 0.21 ( )
2.7 %
Annual increase 0.7%
2.0 %
This slide represents the definite stent thrombosis rate of both stent groups at 2 years follow-up. At one year there was a significant difference which again gradually increases at 2 years follow up.
If one disregards the early stent thrombosis rate, the data suggests that with Taxus Liberte one has annual definite stent thrombosis rate of 0.7%, whereas this is only 0.2% for the Xience V, though the number of events are low and the study was not powered for detecting this difference.
Δ 2.1 %
Δ 1.7 %
Annual increase 0.2%
0.3 %
0.6 %

22. Endpoint Analysis @ 2 yr First Non Fatal MI
Taxus
Xience
P = (log-rank test)
RR = 0.52 ( )
7.6 %
5.4 %
Δ 3.7 %
When looking at the individual components of the composite endpoints, the non fatal MI curves showed a similar outcome to the primary endpoint and stent thrombosis curves. With a significant higher rate of non fatal MI in the Taxus group compared to the Xience group at 12 months follow-up.
Δ 2.6 %
3.9 %
2.8 %

23. Endpoint Analysis @ 2 yr All Death & Cardiac Death
Taxus
Xience
P = 0.67
All
Death
All death and cardiac death rates, however, were similar in both groups
Cardiac
Death
P = 0.49

24. Endpoint Analysis @ 2yr Ischemic driven TVR & TLR
Taxus
Xience
P <
RR = 0.40 (0.25–0.61)
7.7 %
TVR
3.1 %
Taxus
Xience
But TVR and ischemic driven target lesion revascularization rates were highly significantly higher in the Taxus stent group compared to the Xience V stent group. Again with an early difference, which gradually increased over time.
P =
RR = 0.44 ( )
TLR
5.9 %
2.6 %

25. Subgroup analysis @ 2 yr RR ( 95% CI ) Everolimus better Paclitaxel
p value for interaction
0.1
1.0
10.0

26. Conclusions
In this all-comer trial, reflecting a real world patient population, the major secondary endpoints at 2 years showed :
superiority of Xience V versus Taxus Liberté
(p = )
MI, TVR, TLR and Stent thrombosis consistently resulted in significant better outcomes for Xience V compared to Taxus Liberté
Between 1 and 2 years, when the vast majority of patients were no longer taking DAPT, a significant 77% reduction in very late definite or probable stent thrombosis in favour of Xience V was observed
While there was a significant reduction in primary and secondary endpoints in the general patient population with Xience V, no such difference was observed in diabetic patients at 1 and 2 year FU

27. COMPARE TRIAL DSMB Investigators Eric Boersma (chairman) Elvin Kedhi
Eugene McFadden
Carlos van Mieghem
Kaiyum Sheikjoesoef
Peter Smits (PI)
Jochem Wassing
CEC & Core Lab & Statistics
Cardialysis, Rotterdam
DSMB
Eric Boersma (chairman)
Patrick Serruys
Benno Rensing
CEC
Martijn Akkerhuis
Jean-Paul Herrman
Peter Radke
Evelyne Regar
Jeroen Vos
Pascal Vranckx (chairman)
First I would like to thank my co-investigators, the independent DSMB and Clinical Event Committee members and the contract research organisation Cardialysis and last but not least the 1800 patients that were instrumental for completing this study.