1. Peter Smits Maasstad Ziekenhuis Rotterdam The Netherlands
Compare Trial
Peter Smits
Maasstad Ziekenhuis
Rotterdam
The Netherlands

2. 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.

3. Disclosures No personal disclosures
Research Foundation of the Cardiology Department has received unrestricted research grants from:
Abbott Vascular
Boston Scientific
I have no personal disclosures, but the research foundation of my cardiology department has received unrestricted research grants from Abbott Vascular and Boston Scientific.

4. 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

5. Randomized Controlled Trials Pitfalls
AMI
Calcification
Multistenting
Ostial
Thrombus
Long lesions
CTO
Unstable angina
Multivessel
Saphenous graft
Bifurcation
Diabetes
Chronic renal failure
Left main
Diffuse disease
“REAL WORLD”
The large randomized controlled trials have their pitfalls. It’s always debated whether the RCT reflect daily practice. In the RCT often many subsets of patients and/or lesions are excluded; like left main, bifurcation, grafts, CTO, thrombotic, ostial or severe calcified lesions, , but also patients with acute MI, multivessel disease, or chronic renal failure.

6. Compare Trial Purpose of the study
To study the outcome of 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 …..

7. Taxus Liberté Paclitaxel TransluteTM Liberté™ Xience V Everolimus
The Taxus Liberte consists of a thin strut stainless steel stent, coated with Translute - a hydro-carbon elastomer- from which paclitaxel elutes.
The Xience V stent consists of a thin strut cobalt chromium stent , coated with a Fluoropolymer: perfluor elastomer- from which everolimus gradually elutes
Everolimus
Fluoropolymer
VisionTM

8. Strut and Polymer Thickness
CYPHER®
TAXUS® Liberté
ENDEAVOR
XIENCE V
Strut Thickness:
140 mm
Polymer Thickness:
13.7 mm
Strut Thickness:
97 mm
Polymer Thickness:
17.8 mm
Strut Thickness:
91 mm
Polymer Thickness:
4.8 mm
Strut Thickness:
81 mm
Polymer Thickness:
7.8 mm
If we compare the commercially available DES stents, we can see that the Xience V stent has a thinner stent strut and a thinner polymer compared to the Taxus Liberte.
3.0 mm diameter stents, 500x magnification
Data on file at Abbott Vascular.

9. Rapid Re-endothelialization 14-Day Rabbit Iliac Study
XIENCE V
CYPHER®
TAXUS®
ENDEAVOR
Pre-clinical data from a rabbit model, indicates that the everolimus eluting Xience V stent has a more rapid and pronounced re-endothelialization compared to the other commercially available DES, like the Taxus Liberte stent.
Joner M et al. JACC 2008:52:

10. Study Outline Clinical events were adjudicated by an independent CEC
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.
With an expected MACE of 9 versus 14 %, we calculated that with a power of 85%, we needed at least 1800 patients. All patients were monitored during the 1 year follow-up period, only 3 patients out of 1800 patents (0.16%) were lost for follow-up.
Clinical events were adjudicated by an independent CEC and target vessel revascularizations were analysed by an independent core lab.
Clinical events were adjudicated by an independent CEC
Target vessel revascularizations were analysed by an independent QCA core lab.
All patients were monitored for 12 months; only 3 pts (0.16%) were lost for FU.

11. 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

12. 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 at 12 months follow-up.
all death, non fatal MI, TVR at 3 and 5 years
follow-up
incidence of definite, probable or possible stent thrombosis at 12 months, 3 and 5 years

13. 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 at the index procedure of 903 patients randomized to Taxus and 897 patients randomized to Xience V.
The cardiovascular antecedents and risk factors were similar in both patients groups.

14. Clinical Presentation 1800 pts.
Taxus
Xience
Clinical presentation at the index procedure was similar between both groups: % stable angina, 2-3 % silent ischemia, 12 % unstable angina, % non-stemi and 23-26% stemi; indicating that in both groups 60% of the patients presented with an acute coronary syndrome.
± 60% ACS
p = ns

15. 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
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.

16. Lesion Characteristics 1800 patients / 2583 lesions
Taxus
Xience
Lesion characteristics according the ACC/AHA classification showed also a equal distribution between both randomised study groups. With 5-6% type A lesions, …..
Indicating that in both stent groups almost three quarter of the lesions were classified to B2, type C lesions.
73 % B2 / C
74 % B2 / C
p = 0.20

17. 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:………

18. Primary Endpoint Result MACE (all death, non-fatal MI and TVR)
Taxus
Xience
P = (log-rank test)
RR = 0.69 ( )
9.1 %
Δ 2.9 %
Δ 1.1%
6.2 %
This is the result of the primary end-point: the combination of all death, non fatal MI and TVR.
At 12 months follow up, a significant higher incidence of MACE occurred in the Taxus stent group compared to the Xience stent group.
The MACE rate is 9.1% in Taxus versus 6.2% in Xience, which is significant different according the log rank test, with a rate ratio of 0.69 and 95% Confidence Interval of
Of interest is the early difference in events between both groups of 1.1% at 30 days, which gradually increased over time to 2.9% at 12 months follow-up .
# Patients at Risk
Taxus
Xience

19. Secondary Endpoint Result MACE (cardiac death, non-fatal MI and TLR)
Taxus
Xience
P = (log-rank test)
RR = 0.60 ( )
8.2 %
Δ 3.3 %
Δ 1.2 %
This is the result of the secondary endpoint of the combination of cardiac death, non-fatal MI and ischemic driven target lesion revascularization.
Again, a significant difference between both groups at 12 months follow-up, with a 8.2% MACE rate in the Taxus group compared to 4.9 % in the Xience group, which is highly significant different with a p value of and rate ratio of 0.6 with confidence interval below 1.0.
The same early difference in event rate occurred between both stent groups, which gradually increased over time.
4.9 %
# Patients At Risk:
Taxus
Xience

20. Secondary Endpoint Result Stent Thrombosis (Definite & probable according to ARC)
Taxus
Xience
P = (log-rank test)
RR = 0.26 ( )
2.6 %
Definite & probable stent thrombosis rate according to the ARC definitions was also highly significant different between both groups, with a 2.6% in the Taxus group versus 0.7% in the Xience group. This is mainly due to a difference in early stent thrombosis, as shown ……(next dia)
0.7 %

21. Secondary Endpoint Result Early and Late Stent Thrombosis (definite & probable according ARC)
Early ST
Late ST
Taxus
Xience
Taxus
Xience
P = 0.002
P = 0.39
as shown in this landmark presentation of early and late stent thrombosis. In late stent thrombosis no difference was noted.

22. Endpoint Analysis Non Fatal MI
Taxus
Xience
P = (log-rank test)
RR = 0.52 ( )
5.4 %
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.
2.8 %

23. Endpoint Analysis All Death & Cardiac Death
Taxus
Xience
P = 0.58
All
Death
All death and cardiac death rates, however, were similar in both groups
Cardiac
Death
P = 0.81

24. Endpoint Analysis TVR & Ischemic driven TLR
Taxus
Xience
6.0 %
TVR
P =
2.4 %
4.8 %
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.
TLR
P =
1.7 %

25. Conclusions
In an all-comer population, reflecting real world, implantation of the Everolimus eluting Xience V stent significantly reduced major adverse cardiac events compared to the Paclitaxel eluting Taxus Liberté stent
Superiority of the Everolimus eluting Xience V stent
was reached mainly due to less early stent thrombosis and less target lesion revascularization
In an all-comer population, reflecting real world, implantation of the Everolimus eluting Xience V stent significantly reduced major adverse cardiac events compared to the Paclitaxel eluting Taxus Liberté stent in our prospective randomized COMPARE trial.
Superiority of the Everolimus eluting Xience V stent was reached mainly due to less early stent thrombosis and less target lesion revascularization