Breaking Through the Restenosis Barrier: DrugEluting Stents

1
American College of Cardiology 53rd Annual
Scientific Session New Orleans, 2004
REDOX Trial Reduced Sirolimus Doses on the Bx
Velocity Stent 4 - Month Results
J. Eduardo Sousa, Alexandre Abizaid, Fausto
Feres, Luis A. Mattos, Luis F. Tanajura, Amanda
Sousa, Jeffrey Popma, Peter Fitzgerald, Joseph
Giorgianni, Roxanne A. Rodney.
2
Presenter Disclosure Information
REDOX Trial
J. Eduardo Sousa No relationships to disclose
Alexandre Abizaid No relationships to
disclose Fausto Feres No relationships to
disclose Luis A. Mattos No relationships to
disclose Luis F. Tanajura No relationships to
disclose Amanda Sousa No relationships to
disclose Jeffrey Popma No relationships to
disclose Peter Fitzgerald No relationships to
disclose Joseph Giorgianni Cordis
enployee Roxanne A. Rodney Cordis enployee
3
REDOX Feasibility Study

• Background
• The CYPHERTM Sirolimus-Eluting Coronary Stent has
  demonstrated a significant reduction in late
  loss and restenosis in 4 randomized trials.
• The next generation of drug-eluting stents are
  being developed with new materials which have
  potentially less surface area.
• This study was conducted to test the effect of
  reducing the amount of drug on the stent.

4
REDOX Feasibility Study

• Objective
• To assess the performance and safety of two
  reduced (45 and 70 of current dose) sirolimus
  doses on the Bx VELOCITY TM stent in patients
  with de novo native coronary lesions

5
REDOX Feasibility Study

• Study Design
• Single center, randomized
• Patients randomized 11 to the sirolimus-eluting
  Bx VELOCITY containing either 45 or 70 the
  current sirolimus dose
• Patients followed at 30 days, 4 and 12 months,
  and at 2, 3, 4 and 5 years post-procedure, with
  all patients undergoing repeat angiography and
  IVUS at 4 and 12 months

6
REDOX Feasibility Study

• Investigator J. Eduardo Sousa, MD
• Instituto Dante Pazzanese de Cardiologia
• Sao Paolo, Brazil
• Angiographic
• Core Lab Brigham Womens Hospital
• Jeffrey J. Popma, MD
• IVUS Core Lab Sanford University
• Peter Fitzgerald, MD

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REDOX Feasibility Study

• Primary Endpoints - 4 and 12 Months
• Late loss (QCA)
• NIH volume and volumetric plaque burden (IVUS)
• MACE

8
REDOX Feasibility Study

• Key Inclusion Criteria
• Male or non-pregnant female gt 18 years of age
• Single de novo lesion in a native coronary artery
• Target lesion lt18mm in length
• Target vessel gt3.0mm to lt3.5mm in diameter
• Target Stenosis gt50 and lt100
• Visual Estimate

9
REDOX Feasibility Study

• Key Exclusion Criteria
• MI within 72 hours unless enzymes are back to
  norma
• Unprotected left main disease with gt50 stenosis
• Angiographic evidence of thrombus
• Ostial lesions
• EFlt30
• Totally occluded vessel
• Target lesion involves bifurcation

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Demographics
Age (Years) Male Gender Diabetes Hypertension Hy
percolesterolemia Unstable Angina Stable Angina /
Assymp
56.5 23 (74.2) 11 (35.5) 25 (80.6) 20
(64.5) 11 (35.5) 20 (64.5)
55.8 26 (89.7) 9 (31) 16 (55.2) 18
(62.1) 11 (37.9) 18 (62.1)
70 SES n 29

• 45 SES
• n 31

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Procedural Characteristics
Procedure Success Device Success Pre-dilatation
Balloon Length Stent Dimeter 3.0
3.5 Pre-dilatation Balloon
length

• 45 SES
• n 31
• 31 (100)
• 31 (100)
• 16 (51.6)
• 13.5 2.3
• 20 (64.5)
• 11 (35.5)
• 22 (71)
• 13.1 3.6

70 SES n 29 29 (100) 29 (100) 13
(44.8) 13.7 2.1 19 (65.5) 10 (34.5) 17
(59) 13.8 2.4
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Vessel / Lesion Characteristics
Vessel Location LAD Lcx RCA Lesion
Classif A / B1 B2 / C

• 45 SES
• 12 (38.7)
• 7 (22.6)
• 11 (35.5)
• 10 (32.3)
• 21 (67.7)

70 SES 13 (44.8) 6 (20.7) 10 (34.5) 9
(31) 20 (69)
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Pre-Procedures QCA

• 45 SES
• n 31

70 SES n 29
p
2.81 0.46 65 9.7 3 0.4 10 0.35 2.84
0.40
2.86 0.44 68 11.5 3 0.3 0.10 0.32 2.75
0.33
0.666
Reference Diameter DS Pre DS Post MLD Pre MLD
Post
14
QCA Analysis 4 - Month FU

• 45 SES
• n 31

70 SES n 29
p
In-Stent Binary stenosis MLD Late
Loss In-Lesion Binary Stenosis Proximal
Edge Distal Edge MLD Late Loss
0 (0) 2.74 0.39 0.08 0.27 1 (3.2) 1
(3.2) 0 (0) 2.26 0.53 0.10 0.37
1 (3.6) 2.65 0.48 0.08 0.19 2 (7.1) 2
(7.1) 0 (0) 2.35 0.55 0.10 0.36
0.869 0.433 1.000 0.511 0.511 1.000 0.546 0.77
3
15
In-Segment Late Loss

• 45 SES 70 SES

Distal
Proximal
Stent
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IVUS Volumetric Analysis 4 - Month FU

• 45 SES
• n 26

70 SES n 29
p
Vessel Volume (mm3) Stent Volume (mm3) Lumen
Volume (mm3) Intimal Hyperplasia (mm3)
Obstruction ()
289 82 133 36 131 34 3 6.9 2.0 3.6
251 72 122 26 119 29 2.5 5.3 2.6 6.5
0.082 0.207 0.209 0.754 0.684
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IVUS Volumetric Analysis Distribution of
Obstruction

• 45 SES

70 SES
18
Clinical Events up to 6 - Month
In-Hospital MACE 30-Day MACE 6-Month
MACE Death MI (Q Wave) MI (Non-Q) TLR Stent
Thrombosis
70 SES n 29

• 45 SES
• n 31

0 (0) 0 (0) 1 (3.3) 0 (0) 0 (0) 0 (0) 1
(3.3) 0 (0)
0 (0) 0 (0) 2 (6.7) 0 (0) 1 (3.3) 0 (0) 1
(3.3) 0 (0)
19
Diabetic Patients
70 SES n 9

• 45 SES
• n 11

Reference Diameter In-Stent MLD Late
Loss Binary Restenosis In-Lesion MLD Late
Loss Binary Restenosis
2.88 0.5 2.78 0.5 0.01 0.2 0 (0) 2.43
0.5 0.09 0.2 0 (0)
2.83 0.4 2.62 0.4 0.08 0.2 0 (0) 2.31
0.6 0.08 0.4 1 (12.5)
Proximal Edge
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Diabetic Patients IVUS Results at 4 - Month FU
70 SES n 9

• 45 SES
• n 11

Vessel Volume Stent Volume Lumen Volume Intimal
Hyperplasia Obstruction
306 114 134 49 129 35 5.6 11.4 3.2 5.2
247 81 117 25 115 28 2.2 3.6 2.3 3.9
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REDOX Conclusions

• Reducing the normal dose (140 µg/cm2)
• of Sirolimus to 45 and to 70 we observed
• No difference in MACE (3.3 vs. 6.7)
• No difference in QCA late loss (0.08 vs. 0.08mm)
  and binary restenosis (3.2 vs. 7.1)
• No difference in IVUS of stent obstruction (2
  vs 2.6)
• Also there was similar inhibition of neointimal
  formation in diabetic pts (3.2 vs 2.3).
• Changing the SES platform might not
• compromise drug efficacy.