XIENCE V

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XIENCE V
ACC/SCAI 2007 theheart.org March 30th, 2008
James B Hermiller, MD, FACC, FSCAI The Care
Group, LLC St. Vincent Heart Center of
Indiana Indianapolis, IN
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XIENCE V DES
MULTI-LINK VISION Stent
Everolimus
MULTI-LINK VISION Stent Delivery System

• Control Release Coating

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MULTI-LINK VISION Platform

• Cobalt Chromium Technology
• Allows for thinner struts while maintaining
  radiopacity and radial strength

• Thin Strut Stent Design
• Flexible and conformable
• .0032 strut thickness

• Low System Profile
• Excellent deliverability

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Everolimus binds to FKBP-12Inhibiting TOR and
Cell Cycle Progression
FKPB-12, Everolimus, TOR
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Everolimus Inhibits Smooth Muscle Cell
Proliferation with Nanomolar Potency
Everolimus and Sirolimus inhibit vascular smooth
muscle cell proliferation
Sources Novartis Pharma AG Schuler et al.
Transplantation. 1997 6436-42
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XIENCE V Polymer

• Fluoropolymers are biocompatible with a long
  history in blood contacting applications
• Haemodialysis machines
• Cardiac sutures
• Vascular grafts
• Guide catheters
• High drug loading capability
• Minimize coating thickness
• Good physical coating integrity
• Excellent adhesion to metal
• Good ductility and flexibility

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DES Release Profiles (in vivo)
Source Medtronic Vascular Data Presentation,
TCTMD TAXUS IV SR Presentation, TCTMD Cypher
Presentation, TCTMD Data on file at Abbott
Vascular.
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Strut and Polymer Thickness Minimizing Strut and
Polymer Thickness
XIENCETM V
ENDEAVOR
CYPHER
TAXUS Liberté
3.0 mm diameter stents, 500x magnification
Data on file at Abbott Vascular.
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Minimal InflammationPorcine Safety Study up to
720 days
N/A
N/A
N/A
Data on file at Abbott Vascular.
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The XIENCE V SPIRIT Trials
The XIENCE V SPIRIT Family of Trials
XIENCE V USA
SPIRIT V
SPIRIT IV
SPIRIT FIRST
SPIRIT II
SPIRIT III
Post- US Mark Approval
Post- CE Mark Approval
US Peri Approval
Safety Performance
Clinical Support for CE Launch
US Japan Approval
US N 5,000 Registry
International N 3,000 Diabetic study N 300
Registry N 2,700
US N 3,690
Europe N 60
International N 300
US N 1,002
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SPIRIT II Study Design
SPIRIT II
XIENCE V N 223
A maximum of two de novo lesions
RCT 2.5- 4.0 mm N 300
3 1
TAXUS Control N 77

• PI Patrick Serruys, MD, PhD
• RCT Prospective, single blind
• Primary end point in-stent late loss at 6
  months
• Stent Size 2.5 4.0 mm Stent lengths 8, 18,
  28 mm
• Angiographic follow-up baseline, 180 days (300
  patients), and 2 years (152 patients)
• IVUS follow-up baseline, 180 days and 2 years
  (152 patients)
• Clinical follow-up at 1, 6, 9 months, 1 and 2
  years
• 6 Months clopidogrel for all arms

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SPIRIT II 6M Results
Primary Endpoint In-stent Late Loss
IVUS Percent Volume Obstruction
69 reduction p lt 0.0001
66 reduction p lt 0.001
N 100 N 40
N 201 N 73
SOURCE P. Serruys et al., EuroIntervention
2006, 2 286-94.
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SPIRIT III RCT Design
SPIRIT III
XIENCE V N 669
Up to two de novo lesions, maximum of one lesion
per epicardial vessel
Main US RCT 2.5 3.75 mm LL 28 mm N 1,002
2 1
TAXUS Control N 333

• PI Gregg Stone, MD
• RCT Prospective, single blind
• Primary end point In-segment Late Loss at 8M
• Stent Size 2.5 3.5mm mm Stent lengths 8,
  18, 28 mm
• Angiographic and IVUS Follow-Up on 564 and 240
  pts, respectively
• Clinical follow-up at 30, 180, 270d and 1, 2, 3,
  4 and 5 years
• 6 Months clopidogrel for all arms

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SPIRIT III IVUS In-stent Measures at 8 Months
Late AcquiredIncomplete Apposition
EEL volume post-procedure and at 240 days
Diff 95 CI 26 17, 36
Diff 95 CI 4 -5, 12
PNS
305
278
2.3
273
269
127
119
100
100

mm3
1.1
18
50
50
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XIENCE V
TAXUS
XIENCE V
TAXUS
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SPIRIT III 12M Clinical Results
42 reduction
39 reduction RR 95 CI 0.60 0.33, 1.10
RR 95 CI 0.58 0.37, 0.90
10.3
10
8
6.0
5.6
6
Event Rates
4.1
3.4
4
2.8
2
0.9
0.8
0.6
0.5
0
Late Stent
Cardiac Death
MI
TLR
MACE
Thrombosis per
XIENCE V
TAXUS
ARC
SOURCE G.W. Stone, SPIRIT III 12 Month
Presentation, TCT, 2007 SPIRIT III 1 Year Report
. SOURCE G.W. Stone, FDA Panel Sponsor
Presentation 29 November 2007.
MACE Cardiac death, MI, or ischemic TLR, 365
days /- 28 days
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SPIRIT II III Pooled Meta-Analysis
SPIRIT II III
XIENCE V N 892
Meta-Analysis of Patient Level Data
N 1,302
Similar inclusion and exclusion criteria Up to
two de novo lesions, maximum of one lesion per
epicardial vessel 2.5 3.75 mm LL 28 mm
TAXUS Control N 410

• Presented by Gregg Stone, MD at Sponsor FDA Panel
  Presentation, 29 November 2007
• Two prospective, single blind trials with similar
  inclusion and exclusion criteria in 1,302 pts
  with 1,506 lesions
• Independent pooled analysis by academic
  statisticians at the Cardiovascular Research
  Foundation
• Pre-specified superiority testing on all
  endpoints
• All analyses are exploratory and hypothesis
  generating

3 patients in SPIRIT II received 4 mm stents
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SPIRIT II III Angiographic Results
Late Loss
Binary Restenosis
58 Reduction P lt 0.0001
50 Reduction P 0.0004
61 Reduction P 0.02
47 Reduction P 0.039
mm
SOURCE G.W. Stone, SPIRIT II III 9 Month
Meta-Analysis, PCR 2007. Please note that the
data had different angiographic follow-up time
points (6 months vs. 8 months).
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SPIRIT II III Clinical Events 1 Year
48 reduction Plogrank 0.02
48 reduction Plogrank 0.004
Plogrank 0.062
Plogrank 0.32
SOURCE G.W. Stone, FDA Panel Sponsor
Presentation 29 November 2007. Data obtained from
Kaplan Meier Curves.
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SPIRIT II III Safety Results 1 Year
Plogrank 0.002
Plogrank 0.93
Plogrank 0.08
Plogrank 0.39
Plogrank 0.10
SOURCE G.W. Stone, FDA Panel Sponsor
Presentation 29 November 2007. Data obtained
from Kaplan Meier Curves.
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SPIRIT II III 2 Year Safety Subset
Stent Thrombosis
Stent Thrombosis Per Protocol
Stent Thrombosis Per ARC (Definite Probable)
RR 95CI 0.82 0.21, 3.23
RR 95CI 1.02 0.20, 5.21
XIENCE V
TAXUS
XIENCE V
TAXUS
6/379
3/155
5/379
2/155
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SPIRIT II III 2 Year Safety Subset Late/Very
Late Stent Thrombosis (31
days 2 yrs)
Per Protocol
Per ARC (Definite Probable)
RR 95CI 0.55 0.12, 2.41
RR 95CI 0.62 0.10, 3.65
4/378
3/155
3/378
2/153
XIENCE V
TAXUS
XIENCE V
TAXUS
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XIENCE V Summary

• Product Design
• Controlled low everolimus dose for efficacy
• Clinically-proven fluorinated co-polymer
• Thinnest struts for less injury
• Excellent deliverability and conformability
• Clinical Results
• 50 Reduction in in-stent Late Loss vs. TAXUS
• 42 Reduction in Major Adverse Cardiac Events vs.
  TAXUS
• 39 Reduction in TLR vs. TAXUS