1. Trial Vignettes Contemporary trials 3: DES
Angela Hoye
Castle Hill Hospital, Hull
RESOLUTE
MEDISTRA
ABSORB

2. Conflicts of interest Speaker honorarium: Cordis
Advisory board panel: Eli Lilly
Abbott Vascular

3. RESOLUTE  Extended drug-elution
Multicenter study, n=130, PI Prof Meridith
The Endeavor Resolute stent (Medtronic) retains 3 components of Endeavor
Driver Cobalt Chromium Stent
 Extended drug-elution
Endeavor Delivery System
Zotarolimus Antiproliferative Drug

4. The BioLinx Polymer System
Hydrophilic
Zotarolimus
Hydrophobic
Hydrophilic polymer: Polyvinyl pyrrolidinone (PVP) for initial drug burst and enhanced biocompatibility
Hydrophobic polymer: based upon hydrophobic butyl methacrylate (C10) for combining with zotarolimus and uniform drug dispersion
Combination polymer: hydrophobic hexyl methacrylate, hydrophilic vinyl pyrrolidinone and vinyl acetate (C19) to support delayed drug elution and biocompatibility
Polymer is based on the BioLinx Polymer System, a unique blend of hydrophilic and hydrophobic polymers that offers both biocompatibility and extended hydrophobic drug elution. The hydrophilic component is in direct contact with the vessel wall, while maintaining an extended elution of zotarolimus via the control of the hydrophobic polymer blend.

5. Endeavor Resolute Elution
This polymer enables the programming of drug elution and the programmed release of multiple drugs – Resolute is designed to have 90% of the drug eluted into the tissue in the first 90 days with the remainder of the drug completely eluted at 180 days.
Extended in vivo elution kinetics with stent drug content exhausted by 180 days
Carter et al TCT2006

6. Endeavor Resolute Efficacy
28 day results in porcine coronary artery
ENDEAVOR RESOLUTE
DRIVER CONTROL
ENDEAVOR RESOLUTE
Significant inhibition of neointimal development compared to Driver controls
Carter et al TCT2006

7. Clinical Trial Design Clinical/MACE Angio/IVUS
Single De Novo Native Coronary Artery Lesions
Lesion Length: 14-27mm
Stent Diameters: 2.5, 3.0, 3.5mm
Stent Lengths: 18, 24, 30mm (8/9mm bailout)
Drug Dose: 1.6 g/mm2 stent surface area
Antiplatelet therapy for 6 months
Pre-dilatation required
Endeavor Resolute Stent
130 Patients (includes 30 PK Sub-Study Patients)
12 Sites (New Zealand and Australia)
Clinical/MACE
30d
4mo
6mo
9mo
12mo
2yr
3yr
4 yr
5 yr
Angio/IVUS
Based on the excellent performance of the three key elements of the Endeavor DES system and the comparable biocompatibility and superior efficacy results of the bioLinx polymer in experimental studies, a CE mark clinical trial was initiated the design of which is shown here
N=30
N=100
Primary Endpoint: Late lumen loss (in-stent) at 9 months by QCA
Secondary Endpoints: MACE at 30 days, 6, 9 and 12mths and IVUS and
angiographic parameters at 9mths
9 month results will be compared to ENDEAVOR II DES cohort
30 pt Subset: 4mth MACE and angiographic, IVUS parameters

8. Patient Demographics Male 75.4% (98/130) Age 61 + 10yrs (130) Prior MI
45.7%
(59/129)
Prior PCI
18.5%
(24/130)
Diabetes Mellitus
17.7%
(23/130)
Insulin Dependent
2.3%
(3/130)
Unstable Angina
29.7%
(38/128)
Hyperlipidemia
94.6%
(123/130)
Current Smoker – within last 30 days
22.3%
(29/130)

9. Procedural Results Entire patient cohort 130 pts/131 lesions
Lesion Length mm
LAD
34.4% (45/131)
B2/C Lesions
82.4% (108/131)
Device success
99.2%
Procedure success
96.2%
This procedural results for the entire pt cohort these results will be presented in full along with the 9mnth angiographic results at PCR
Lesion success <50% residual in-segment % ds
Device success <50% residual in-segment % ds with assigned stent
Procedure success <50% residual in-segment % ds & without 30-day MACE

10. Clinical Results to 30 days
Entire patient cohort
n = 130
MACE (%)
3.8
(5/130)
Death
(0/130)
Q-Wave MI
Non Q-Wave MI
Emergent CABG
TLR
TL-CABG
TL-PCI
TVR (non-TL) (%)
Stent Thrombosis (%)
There was a 3.8% MACE rate comprised entirely of peri procedural non Q wave MIs, there where no TLR, TVR or ST in this pt cohort

11. Angiographic results Subset n=30 In-stent In-segment RVD (mm)
2.90±0.38
Lesion Length (mm)
MLD (mm) pre
post
2.81±0.36
2.43±0.45
Acute Gain
1.98±0.45
1.61±0.59
MLD (mm) 4 mo f/u
2.68±0.39
2.38±0.40
Late Loss (mm)
0.12±0.26
0.05±0.20
Late Loss Index
% DS
7.18±7.86
17.74±7.57
ABR (%)
This is the key slide in the presentation I draw you attention to the fact that the reference Vessel dimension was 2.9mm which was slightly larger than the E2 population but the LL at 15mm being slightly longer than in E2

12. IVUS Volumetric Results
Subset n=30
Post Procedure
4 mo Follow up
EEM Volume
mm3
mm3
Stent Volume
mm3
mm3
Neointimal Volume
mm3
mm3
Post Stent
Follow up
6.7 ± 1.6
6.8 ± 1.7
P=NS
(mm2) 2 6 4 8 10
IVUS Cross-sectional area results: (serial IVUS (2D & 3D analysis, n=29)

13. Conclusions Excellent rate of device, lesion and procedural success
Low clinical adverse event rate at 30 days
The angiographic and IVUS results observed in the 4 month subset demonstrated low late loss, and minimal neointimal hyperplastic in-growth

14. Medistra Excel Drug-ElutIng Stent TRiAl Biodegradable PLA polymer
Single center registry of “real world” cases
PI Dr Santoso, Medistra Hospital, Jakarta
Platform: S-Stent Strut thickness ”
Carrier :
Biodegradable PLA polymer
Drug :
Sirolimus
EXCEL
JW Technologies
Strut ”
Polymer coated on the outer stent surface and release the drug only toward the vessel wall
40％of Sirolimus released in an initial 24 h, followed by a constant slow release (3-6 months)
Lower cost: $1,200

15. 28-day preclinical study results
without Sirolimus with Sirolimus

16. Medistra Excel Drug-ElutIng Stent TRiAl
Single center, prospective, observational study ( )
Study NOT sponsored by the company
Inclusions:
All comers who are candidates for PCI
(“real world cases”)
Exclusions:
Contraindications to anti-platelets
Patients with short life expectancy & serious concomitant disease (advanced cancer, etc)
Lack of patient’s consent

17. Medistra Excel Drug-ElutIng Stent TRiAl
Primary End-Point:
TLR at 6 and 12 months
Secondary End-Points:
6-month in-segment restenosis rate
In-segment late loss
Major Adverse Cardiac Events (MACE):
Death, QMI, NQMI, & / or TLR
QCA analysis was done by an independent core laboratory
(National Heart Centre - Singapore)
(Dr. A. Wong, A/Prof. T.H. Koh)

18. Medistra Excel Drug-ElutIng Stent TRiAl
Predilatation is encouraged, even though direct stenting
is allowed in simple lesion
Stent selection:
Try to always use EXCEL
If appropriate size / length not available, use other DES
(Cypher or Taxus)
If other DES is not available (logistic problem), use
BMS
Antiplatelet regimen:
ASA 160 mg indefinitely (unless contraindicated)
Clopidogrel 300 mg (loading), then 75 mg for 6 months

19. Methods 277 eligible pts, 631 lesions All comers, N = 279
2 stent dislodgement* (“prototype stent”)
277 eligible pts, 631 lesions
DES-stenting as default strategy (N=771 stents),
except if there is logistic problem (BMS will be used)
61% Excel
EXCEL
N=470
CYPHER
N=137
TAXUS
N=86
BIOMATRIX
N=27
ENDEAVOUR
N=5
BMS
N=46
61% of stents
* 1 case when negotiating mildly stenotic, acutely angulated LCX to fix mid-LCX stenosis
1 case with diffuse, calcified mid-RCA stenosis, during attempted direct stenting

20. Demographics (n=277) Age (yrs) 58.5 + 9.4 Male 226 (81.6%)
Family history 97 (35. 0%)
Hypertension 152 (54.9%)
Dyslipidemia 160 (57.8%)
Diabetes mellitus 110 (39.7%)
Smoking (43.0%)
Prior MI (44.4%)
Prior CABG 14 (5.0%)
Prior PCI 77 (22.8%)

21. Clinical Presentation
Stable angina (48.0%)
Unstable angina / ACS 32 (11.6%)
Acute MI (4.0%)
Recent MI ( < 30 days) 15 (5.4%)
Silent ischemia 86 (31.0%)
LVEF (%, mean + SD) %

22. Lesion types %

23. Stent Diameter (n=771 stents)
EXCEL (n=470)
TAXUS (n=86) % %
BMS (n=46)
CYPHER (n=137) % %
BIOMATRIX (n=27): 2.5 mm:16; 3 mm:5; 3.5 mm:3; 4 mm:3
ENDEAVOUR (n=5): 2.5 mm:2; 3 mm:2; 3.5 mm:2

24. Clinical results 30 days 6 months 12 months No. pts 232 (84%)
210 (76%)
154 (51%)
Death
2 (0.9%) *+
2 (1.0%)
2 (1.3%)
Non-fatal MI
TLR/TVR
1 (0.4%)*
4 (1.9%)
6 (3.9%)
CABG
Stent thrombosis
2 (0.9%)*
2 (1.0%)
2 (1.3%)
* Pt with diffuse small LAD disease, multiple overlapped Cypher & Excel stents
+ Pt with triple, small vessel disease, died 1 week after PCI (5 stents: Excel, BioMatrix & Cypher)

25. QCA analysis at 6 months (independent QCA lab – NHC, Singapore)
34% of the total patient cohort
QCA analysis: 94 pts with 217 lesions
Types of Stents used (per lesion)
Cypher Taxus EXCEL BMS
(n=34) (n=30) (n=138) (n=15)
Lesion length(mm)
Stent size (mm)
Stent length (mm)

26. QCA analysis at 6 months CYPHER TAXUS EXCEL BMS Pre procedural
RVD, mm
MLD, mm
DS, %
Post procedural
MLD, mm
DS, %
Follow-up (6 months)
MLD, mm
DS, %
Binary restenosis 18% 10% 5% 17%
Late loss, mm
In-segment (p=0.12) (p=0.03) (p=0.003)
In-stent
(p=0.055) (p=0.004) (p<0.001)

27. the preliminary EXCEL results are encouraging,
Conclusion
Despite the inclusion of challenging “real world cases” (DM, MVD, small vessel, complex lesions, long – diffuse disease, calcified stenosis, ostial stenosis, LM, AMI, CTO, instent restenosis, etc)
the preliminary EXCEL results are encouraging,
with very low MACE rate & “clean” angiographic appearance of the stent.

28. Bioabsorbable Polymer Coating
ABSORB study
FIM study of the BVS everolimus-eluting bioabsorbable stent from Abbott Vascular
Preliminary results presented by Dr J Ormiston
ML VISION™ Balloon SDS
BVS bioabsorbable stent platform
A polymeric stent made from linked polylactic acid molecules that break down into lactic acid
Everolimus
Bioabsorbable Polymer Coating

29. Porcine Coronary Artery Safety Study: Representative Photomicrographs (10x)
BVS
28 Day
90 Day
180 Day
270 Day
Competitive Metallic DES*
28 Day
BVS stents (current design) and CYPHER stents were implanted into porcine coronary arteries and evaluated, and compared, at multiple time points. The neointimal response was comparable to the two implants at 28 and 90 days in terms of neointimal composition and coverage. At later time points, however, the neointimal response to BVS stents was milder. BVS stent elicited minimal to no inflammation in contrast to the competitive metallic DES ( CYPHER) which elicited a marked inflammatory response at later time points, which translated into a greater neointimal response.
For BVS stents, the stent struts were completely incorporated within a thin neointima with complete luminal endothelialization at all time points evaluated. Peri-strut fibrin was observed at 28 days consistent with a drug effect which was resolved by 90 days consistent with drug elution off of the stent. This observation was similar to that seen with competitive metallic DES systems. The media remained healthy and intact at all time points consistent with a non-cytotoxic drug. In summary the neointimal response to the BVS stent has been minimal and benign overall out to 9 months post implantation in a porcine model.
90 Day
180 Day
270 Day
*CYPHER
SE /B
Product currently in development at Abbott Vascular. Not available for sale.

30. ABSORB STUDY
FIM study of 30 patients with single de novo native lesions
The stent used was 3.0 x 12 mm
Cypher stents were used if necessary as “bailout”
PIs Dr Ormiston, Prof Serruys
Pre
Final
Product currently in development at Abbott Vascular. Not available for sale.
SE /B

31. Baseline Lesion Characteristics: Acute Success
Location:
LAD
47%
RCA
23%
LCx
30%
Lesion classification: B1
60% B2
40%
Clinical device success:
93.5%
- successful delivery & deployment of stent with final residual DS of <50%. Bailout patients will be included as device success only if the above criteria for clinical device are met.
Clinical procedure success:
100%
- definition above and/or using any adjunctive device without occurrence of ischemia driven MACE during first 7 days
Bailout Stents = 4 patients: Two patients had procedure dissections treated with single CYPHER® stents, one patient received a CYPHER® stent for vessel step-down and one patient received three CYPHER® stents to treat the target lesion.

32. In-Stent Baseline QCA Pre-procedure N = 30 Post-procedure N = 26* 9.05
Lesion length (mm)
RVD (mm)
MLD (mm)
DS (%)
9.05
2.69
1.06 60
N = 26*
Post-procedure
Acute gain (mm)
2.31 17
1.22
* Per treatment evaluable population. Four patients excluded that received a non-BVS bail out stent, including one patient that did not receive a BVS stent at the target lesion

33. Acute Recoil (n=27*) Average of Mean Lumen Diameter (mm) 6.85%
Stent
Expansion
Post Stent
Expansion
Absolute Stent
Recoil
Relative Stent
Recoil
2.86
2.67
0.20
6.85%
Ref: S. Tanimoto et al: Acute Stent Recoil of a Bioabsorbable Everolimus Eluting Coronary Stent: In Vivo Evaluation; e-Poster presentation number 306, TCT 2006.
Recoil rate for XIENCE™ V stent 4.27% (p=0.25)
*Subgroup analysis, recoil data not available in three patients

34. Clinical Results Hierarchical MACE at 30 N = 26 Days Cardiac Death %
Myocardial Infarction %
Q-wave MI
Non Q-wave MI
Ischemia driven TLR %
CABG
PCI
MACE %
Stent thrombosis %

35. Conclusions
In this FIM study of a bioabsorbable everolimus-eluting stent, there was low acute stent recoil
There was a high rate of procedural success (100%)
At 30 days, there were no cardiac deaths, no MI, no stent thrombosis, and no TLR

36. Thankyou Summary Encouraging preliminary results with all three stents
Zotarolimus-eluting Endeavor Resolute stent (Medtronic)
Sirolimus-eluting Excel stent (JW Technologies)
Bioabsorbable everolimus-eluting stent (Abbott Vascular)
Thankyou