Trial Vignettes Contemporary trials 3: DES

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Trial VignettesContemporary trials 3 DES

• Angela Hoye
• Castle Hill Hospital, Hull

• RESOLUTE
• MEDISTRA
• ABSORB

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Conflicts of interest

• Speaker honorarium Cordis
• Advisory board panel Eli Lilly
• Abbott
  Vascular

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RESOLUTE

• Multicenter study, n130, 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
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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
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Endeavor Resolute Elution
Extended in vivo elution kinetics with stent drug
content exhausted by 180 days
Carter et al TCT2006
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Endeavor Resolute Efficacy
28 day results in porcine coronary artery
ENDEAVOR RESOLUTE
DRIVER CONTROL
ENDEAVORRESOLUTE
Significant inhibition of neointimal development
compared to Driver controls
Carter et al TCT2006
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Clinical Trial Design
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
6mo
4 yr
3yr
2yr
9mo
12mo
5 yr
4mo
Angio/IVUS
N30
N100
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
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Patient Demographics
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Procedural Results
130 pts/131 lesions
Entire patient cohort
Lesion success lt50 residual in-segment
ds Device success lt50 residual in-segment ds
with assigned stent Procedure success lt50
residual in-segment ds without 30-day MACE
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Clinical Results to 30 days
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Angiographic results
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IVUS Volumetric Results
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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

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Medistra Excel Drug-ElutIng Stent TRiAl

• Single center registry of real world cases
• PI Dr Santoso, Medistra Hospital, Jakarta

Platform S-Stent Strut thickness 0.0047
Carrier Biodegradable PLA polymer
Drug Sirolimus
EXCEL JW Technologies
40of Sirolimus released in an initial 24 h,
followed by a constant slow release (3-6 months)
Lower cost 1,200
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28-day preclinical study results
without Sirolimus with
Sirolimus
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Medistra Excel Drug-ElutIng Stent TRiAl

• Single center, prospective, observational study
  (2004-06)
• 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 patients consent

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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)
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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

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Methods
All comers, N 279
2 stent dislodgement (prototype stent)
277 eligible pts, 631 lesions
DES-stenting as default strategy (N771 stents),
except if there is logistic problem (BMS will be
used)
EXCEL N470
CYPHER N137
TAXUS N86
BMS N46
BIOMATRIX N27
ENDEAVOUR N5
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
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Demographics (n277)

• 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 119 (43.0)
• Prior MI 123 (44.4)
• Prior CABG 14 (5.0)
• Prior PCI 77 (22.8)

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Clinical Presentation

• Clinical presentation
• Stable angina 133 (48.0)
• Unstable angina / ACS 32 (11.6)
• Acute MI 11 (4.0)
• Recent MI ( lt 30 days) 15 (5.4)
• Silent ischemia 86 (31.0)
• LVEF (, mean SD) 59 11

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Lesion types

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Stent Diameter (n771 stents)
TAXUS (n86)
EXCEL (n470)


BMS (n46)
CYPHER (n137)


BIOMATRIX (n27) 2.5 mm16 3 mm5 3.5 mm3 4
mm3 ENDEAVOUR (n5) 2.5 mm2 3 mm2 3.5 mm2
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Clinical results
12 months
6 months
30 days
154 (51)
210 (76)
232 (84)
No. pts
2 (1.3)
2 (1.0)
2 (0.9)
Death
0
0
0
Non-fatal MI
6 (3.9)
4 (1.9)
1 (0.4)
TLR/TVR
0
0
0
CABG
2 (1.3)
2 (1.0)
2 (0.9)
Stent thrombosis
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)
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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 (n34) (n30) (n
138) (n15) Lesion length(mm) 15.8 18.3 15.8
12.3 Stent size (mm) 2.85 2.87 2.86 3.50 Stent
length (mm) 22.5 26.8 21.7 16.8
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QCA analysis at 6 months
CYPHER TAXUS EXCEL BMS
Pre procedural RVD, mm
2.60 2.57 2.53 3.20 MLD, mm
0.93 0.95 0.97 1.09 DS,
57.3 62.2 60.0 66.0 Post procedural MLD, mm
2.13 2.11 2.08 2.73 DS,
17.7 18.8 17.7 12.8 Follow-up (6 months) MLD,
mm 1.89 1.78 2.07 2.06 DS,
29.2 31.7 21.6 35.9 Binary restenosis 18
10 5 17 Late loss, mm In-segment
0.24 0.31 0.01 0.55
(p0.12) (p0.03)
(p0.003) In-stent
0.25 0.35 0.07 0.59 (p0.055)
(p0.004) (plt0.001)
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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.
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ABSORB study

• FIM study of the BVS everolimus-eluting
  bioabsorbable stent from Abbott Vascular
• Preliminary results presented by Dr J Ormiston

BVS bioabsorbable stent platform A polymeric
stent made from linked polylactic acid molecules
that break down into lactic acid
ML VISIONBalloon SDS
Everolimus
BioabsorbablePolymer Coating
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Porcine Coronary Artery Safety Study
Representative Photomicrographs (10x)
BVS
28 Day
90 Day
180 Day
270 Day
Competitive Metallic DES
270 Day
180 Day
90 Day
28 Day

CYPHER
Product currently in development at Abbott
Vascular. Not available for sale.
SE 2925096/B
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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

Product currently in development at Abbott
Vascular. Not available for sale.
SE 2925096/B
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Baseline Lesion Characteristics Acute Success
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.
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In-Stent Baseline QCA
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
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Acute Recoil (n27)
Average of Mean Lumen Diameter (mm)
Relative Stent Recoil
Stent Expansion
Absolute Stent Recoil
Post Stent Expansion
2.86
6.85
2.67
0.20
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 (p0.25)
Subgroup analysis, recoil data not available in
three patients
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Clinical Results
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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

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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