Transcript Comparison of EVEREST II High Surgical Risk and Continued Access High Surgical Risk Patient Cohorts 1 Year Preliminary Results Michael Rinaldi, Saibal Kar, Scott.

Comparison of EVEREST II High Surgical Risk
and Continued Access High Surgical Risk
Patient Cohorts
1 Year Preliminary Results
Michael Rinaldi, Saibal Kar, Scott Lim,
Ted Feldman, and the EVEREST II Investigators
SCAI 2011
Baltimore, MD
1
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Investigational Device only in the U.S. Not available for sale in the U.S.
Disclosures
 Consulting Fees/Honoraria
• Abbott Vascular
2
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Investigational Device only in the U.S. Not available for sale in the U.S.
Percutaneous Mitral Valve Repair
MitraClip® System
3
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Investigational Device only in the U.S. Not available for sale in the U.S.
MitraClip Therapy
Worldwide Clinical Experience
 Over 3,000 patients have been treated with the
MitraClip device worldwide:
• 75% are considered high risk* for mitral valve surgery
• 67% have functional mitral regurgitation (MR)
 1,453 patients have been enrolled in prospective
clinical trials worldwide:
• 50% are considered high risk* for mitral valve surgery
• 60% have functional MR
Estimates of worldwide clinical experience as of March 31, 2011
* Determination of high surgical risk based on: logistic EuroSCORE ≥ 20%, or STS calculated mortality ≥ 12%,
or pre-specified high surgical risk comorbidities.
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Investigational Device only in the U.S. Not available for sale in the U.S.
High Surgical Risk Patients Treated with the
MitraClip Device in EVEREST II Trials
EVEREST High Surgical Risk Clinical Trials
78
EVEREST II – High Risk Trial
EVEREST II Continued Access – High Risk Trial
294
TOTAL High Surgical Risk Patients
372
As of April 12, 2011
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Background
EVEREST II Outcomes Through 2 Years
 Randomized Controlled Trial (RCT) comparing
percutaneous device and mitral valve surgery
• Percutaneous repair provides increased safety
• Surgery provides more complete MR reduction
• Both percutaneous and surgical treatment reduced MR
and demonstrated significant clinical benefits
 High Risk study evaluating MitraClip device
• Patients experienced reduced MR and significant
clinical benefits
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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EVEREST II Continued Access Investigators
T Feldman, J Alexander, R Curran, E Chedrawy, S Smart, M Lampert
A Wang, D Glower, J Jollis
M Kellett, P Weldner, R Quinn
R Quesada, J Lamelas, N Moreno, R Machado
P Grayburn, B Hamman, R Hebeler, M Mack, W Ryan
V Rajagopal, J Kauten, W Mashman
J Hermiller, D Heimansohn, K Allen, D Segar
M Rinaldi, E Skipper, R Steigel, J Cook, G Rose
S Kar, G Fontana, A Trento, R Kass, W Cheng, R Siegel, K Tolstrup
P Whitlow, T Mihaljevic, N Smidera, L Svenssen, E Roselli, L Rodriquez, W Stewart
W Gray, A Stewart, M Williams, M Argenziano, S Homma, R Pizzarello, L Gillam
D Steinberg, F Crawford, J Ikonimidis, D Gregg, P Zwerner
B Whisenant, S Clayson, B Reid, S Horton, J Orford
R Smalling, G Letsou, J Walkes, C Loghin
W Pedersen, V Kshettry, F Eales, T Flavin, T Kroshus, R Bae
C Rammohan, C Vial, R Beygui, D Nair, A Prakash
SC Wong, OW Isom, L Girardi, K Krieger, R Devereux, R Mishra
J Slater, A Galloway, G Perk, I Kronzon
C Ruiz, D Loulmet, V Subramanian, I Kronzon, N Marino
R Kipperman, S Lucas, RM Bodenhamer, J Randolph, J Williams
Z Hijazi, R March, K Cao, J Soble
P Kramer, B Castlemain, A Schwartz, L Crouse, V Pasnoori
A Berke, N Robinson, R Colangelo, P Damus, H Fernandez, J Taylor, N Bercow, A Katz
T Bajwa, D O’Hair, D Kress, K Sagar
M Sanz, S Tahta, JM Maxwell, B Berry, J Knapp
M Reisman, W Curtis, D Gartman, J Teply, D Warth, K Krabill
P Fail, K Paape, T Fudge, M Trotter, M Allam, E Feinberg, V Tedesco, D Solet
R Low, N Young, K Shankar, R Calhoun, W Bommer
J Carroll, J Cleveland, R Quaife
H Herrmann, M Acker, YJ Woo, F Silvestry, S Wiegers
S Bailey, E Sako, J Erikson
DS Lim, I Kron, J Kern, J Dent, H Gutgesell
R Kipperman, J Brown, D Cohen, H Hamrah
K Kent, S Boyce. P Sears-Rogan
J Lasala, M Moon, R Damiano, B Lindman, A Zajarias, J Madrazo
G Hanzel, F Shannon, M Sakwa, A Abbas, M Gallagher, P Markovitz
NorthShore University HealthSystem, Evanston, IL
Duke University, Durham, NC
Maine Medical Center, Portland, ME
Baptist Hospital of Miami, Miami, FL
Baylor University Medical Center, Dallas, TX
Piedmont Hospital, Atlanta, GA
The Care Group, Indianapolis, IN
Carolinas Medical Center, Charlotte, NC
Cedars-Sinai Medical Center, Los Angeles, CA
The Cleveland Clinic, Cleveland, OH
Columbia University, New York, NY; Danville, CT
Medical University of South Carolina, Charleston, SC
Latter Day Saints Hospital, Salt Lake City, UT
Memorial Hermann Hospital, Houston, TX
Minneapolis Heart Institute, Minneapolis, MN
El Camino Hospital, Mountain View, CA
New York Presbyterian Hospital, New York, NY
NYU Medical Center, New York, NY
Lenox Hill Hospital, New York, NY
Oklahoma Heart Hospital, Okalahoma City, OK
Rush University Medical Center, Chicago, IL
Shawnee Mission Medical Center, Shawnee Mission, KS
St. Francis Hospital, Long Island, NY
St. Luke’s Medical Center, Milwaukee, WI
St. Patrick's Hospital & Health Science Ctr, Missoula, MT
Swedish Medical Center, Seattle, WA
Terrebonne General Medical Center, Houma, LA
University of California at Davis, Sacramento, CA
University of Colorado Health Sciences Center, Denver, CO
University of Pennsylvania, Philadelphia, PA
University of Texas Health Sciences Ctr, San Antonio, TX
University of Virginia, Charlottesville, VA
Morristown Memorial Hospital, Morristown, NJ
Washington Hospital Center, Washington DC
Washington University Medical Center, St. Louis, MO
William Beaumont Hospital, Royal Oak, MI
Interventional Cardiologist, Cardiac Surgeon, Echocardiologist
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Investigational Device only in the U.S. Not available for sale in the U.S.
Purpose
 To present initial safety and effectiveness data of
MitraClip device in Continued Access “real world”
high surgical risk patients
• Enrollment is ongoing
 To compare initial Continued Access high surgical
risk study results to EVEREST II high surgical risk
study results
 To assess the impact of operator learning on
outcomes of high surgical risk patients
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Investigational Device only in the U.S. Not available for sale in the U.S.
Key Eligibility Criteria
EVEREST II and Continued Access High Surgical Risk Patients
All high risk patients were enrolled using the same inclusion/exclusion criteria
KEY INCLUSION CRITERIA
• Predicted procedural mortality risk ≥ 12%
(STS calculated or Surgeon estimated based
on specific co-morbidities)
• Symptomatic significant (3+ or 4+) MR
• Etiology: Degenerative or Functional
• Primary regurgitant jet originates from leaflet
mal-coaptation at A2 / P2 region
KEY EXCLUSION CRITERIA
• Evidence of an AMI in 2 weeks prior
• EF ≤ 20% and/or LVESD > 60mm
• Leaflet anatomy which may preclude
MitraClip device implantation / proper
positioning
• Prior MV leaflet surgery
• Echo evidence of intra-cardiac mass,
thrombus, vegetation
• Active endocarditis
• Clip implant criteria
• Mitral valve area < 4 cm2
• Flail gap ≥ 10 mm,
• Flail width ≥ 15 mm
•Coaptation length < 2 mm
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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High Surgical Risk Concurrent Control Group
 Control group includes 36 patients screened for
EVEREST II – High Surgical Risk
• All patients met clinical eligibility criteria
• All patients had significant MR (3+ to 4+) and met
high surgical risk criteria
 Baseline co-morbidities well matched with
EVEREST II High Surgical Risk Cohort
 Management of MR through 1 year
• 86% medical management
• 14% mitral valve surgery
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Mitral Valve Anatomic Criteria
High Surgical Risk Concurrent Control
(N=36)
0%
10%
Met all MitraClip anatomic criteria
30%
40%
22%
20%
No TEE performed
Leaflet calcification
19%
MVA<4.0cm2
11%
Jet origin other than A2-P2
11%
8%
Captation length >2mm
Flail width >15mm, or flail gap >10mm
20%
6%
Severely retracted posterior leaflet 3%
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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EVEREST II High Surgical Risk Cohort
Enrollment
EVEREST II High Surgical Risk Cohort
N = 372*
EVEREST High Surgical Risk Trial^
N = 78 Enrolled
REALISM High Surgical Risk Trial^
N = 294 Enrolled
1 Year
N = 78
1 Year
N = 133
EVEREST II High Surgical Risk Cohort
With 1 Year Follow-Up^
N = 211
* As of April 12, 2011, ^ Enrolled by February 28, 2010
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Patient Accountability
EVEREST II and Continued Access High Surgical Risk Patients
211 EVEREST II
High Surgical Risk Patients
With 1 Year Follow-up
EVEREST II
High Surgical Risk Patients
N = 78
Continued Access
High Surgical Risk Patients
N = 133
N=5
Withdrawals
N=3
Withdrawals
N = 128
1 Year Analysis
N = 75
1 Year Analysis
Enrolled by 28 Feb 2010
96% of patient data
available for analysis
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Baseline Demographics and Co-Morbidities
EVEREST II and Continued Access High Surgical Risk Patients
EVEREST II
High Surgical Risk
Patients
(N = 78)
Continued Access
High Surgical Risk
Patients
(N = 133)
p-value
Age, years, Mean ± SD
77 ± 10
76 ±11
0.43
Estimated Mortality Risk* (%)
18 ± 8
19 ± 8
0.73
Gender, male (%)
63
59
0.66
Coronary Artery Disease (%)
84
80
0.47
Atrial Fibrillation (%)
62
65
0.76
Moderate – Severe Renal Disease (%)
23
35
0.07
Prior CV Surgery (%)
59
58
0.89
Prior MI (%)
56
45
0.15
NYHA Class III/IV (%)
90
84
0.23
Functional MR (%)
59
78
0.008
LVEF, Mean ± SD (%)
54 ± 14
46 ± 13
< 0.001
LVID-s, Mean (cm)
3.9 ±1.1
4.5 ± 1.0
< 0.001
*STS risk calculated or surgeon estimate based on prespecified co-morbidities
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Implant Rate and Procedural Results
EVEREST II and Continued Access High Surgical Risk Patients
EVEREST II
High Surgical Risk
Patients
(N = 78)
Continued Access
High Surgical Risk
Patients
(N = 133)
p-value
96
95
0.80
0 MitraClips
4
5
n/a
1 MitraClip
59
62
n/a
2 MitraClips
37
33
n/a
MR ≤ 2+ at discharge, all patients (%)
72
88
0.009
MR ≤ 2+ at discharge for patients with
MR ≥ 3+ at baseline (%)
71
81
0.20
Mean Procedure Time
190
153
< 0.001
Mean Device Time
145
117
0.005
Mean Fluoroscopy Duration
53
39
< 0.001
MitraClip Implant Rate (%)
Procedural Results (min)
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Implant Rate and Procedural Results
EVEREST II and Continued Access High Surgical Risk Patients
EVEREST II
High Surgical Risk
Patients
(N = 78)
Continued Access
High Surgical Risk
Patients
(N = 133)
p-value
ICU Duration (hours)
52
25
0.005
Hospital Stay (days)
3.9
2.5
0.05
Home
80
87
Home With Home Health Care
10
8
Nursing Facility
10
3
Died Prior to Discharge
4
2
Post-Procedural Results
Discharged To, (%)
0.26
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Predicted vs Observed 30 Day Mortality
EVEREST II and Continued Access High Surgical Risk Patients
20
P = 0.006
P < 0.0001
18
% Mortality
16
18.2%
Predicted
Observed
18.2%
14
12
P = 0.34
10
8
6
7.7%
4
2
3.8%
0
EVEREST II HR
Continued Access HR
N = 78
N = 133
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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30 Day MAE
EVEREST II and Continued Access High Surgical Risk Patients
EVEREST II
High Surgical Risk
Patients
(N = 78)
# (%) Patients
Continued Access
High Surgical Risk
Patients
(N = 133)
# (%) Patients
p-value
Death
6 (7.7%)
5 (3.8%)
0.34
Major Stroke
2 (2.6%)
4 (3.0%)
> 0.99
Re-operation of Mitral-Valve
0
0
n/a
Urgent / Emergent CV Surgery
0
1 (0.8%)
> 0.99
Myocardial Infarction
2 (2.6%)
1 (0.8%)
0.56
Renal Failure
3 (3.8%)
1 (0.8%)
0.14
0
0
n/a
2 (2.6%)
2 (1.5%)
0.63
New Onset Permanent Atrial Fib
0
0
n/a
Septicemia
0
1 (0.8%)
> 0.99
1 (1.3%)
0
0.37
14 (17.9%)
16 (12.0%)
0.31
Total
21 (26.9%)
22 (16.5%)
0.08
Total Excluding Transfusions
10 (12.8%)
10 (7.5%)
0.23
Deep Wound Infection
Ventilation >48 hrs
GI Complication Requiring Surgery
Transfusions ≥ 2 Units
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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18
Investigator MitraClip Procedure Experience
EVEREST II and Continued Access High Surgical Risk Patients
EVEREST II
High Surgical Risk
Patients
(N = 78)
Continued Access
High Surgical Risk
Patients
(N = 133)
Number of Operators
25
34
Operator Experience:
Rolling average number of cases
performed
10
23
7 (5, 16)
17 (8, 27)
Median (Inter-quartile range)
p-value
< 0.0001
* Includes patients treated in all EVEREST studies
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Baseline Demographics and Co-Morbidities
EVEREST II, Continued Access and Concurrent Control
EVEREST II
High Risk Patients
(N = 78)
Continued Access
High Risk Patients
(N = 133)
Concurrent
Control
(N = 36)
Age, years, Mean ± SD
77 ± 10
76 ±11
77 ± 13
Estimated Mortality Risk (%)
18 ± 8
19 ± 8
17 ± 7
Gender, male (%)
63
59
50
Coronary Artery Disease (%)
84
80
71
Atrial Fibrillation (%)
62
65
53
Moderate – Severe
Renal Disease (%)
23
35
31
Prior CV Surgery (%)
59
58
53
Prior MI (%)
56
45
36
NYHA Class III/IV (%)
90
84
84
Functional MR (%)
59
78
64
LVEF, Mean ± SD (%)
54 ± 14
46 ± 13^
55 ± 18
LVID-s, Mean (cm)
3.9 ±1.1
4.5 ±1.0^
3.8 ±1.1
^p<0.001, REALISM HR vs CC
20
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Kaplan-Meier Freedom from Death At 1 Year
EVEREST II, Continued Access and Concurrent Control
Freedom from Death
1.0
0.8
0.6
0.4
At 1 Year
EVEREST II High Risk 75.6%
0.2
Continued Access High Risk 75.2%
Concurrent Control
55.6%
p = 0.048 vs CC
p = 0.008 vs CC
0.0
60
0
120
180
240
300
42
360
Days from Index Procedure
# At Risk
EVEREST II High Risk
REALISM High Risk
Concurrent Control
0 Days
78
133
36
30 Days
72
126
32
6m
64
115
28
1yr
58
53
20
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Kaplan-Meier Freedom from MV Surgery At 1 Year
EVEREST II and Continued Access High Surgical Risk Patients
Freedom from MV Surgery
1.0
0.8
At 1 Year
EVEREST II High Risk 100%
0.6
Continued Access High Risk 96.8%
0.4
0.2
0.0
0
60
120
180
240
300
360
42
Days from Index Procedure
# At Risk
EVEREST II High Risk
REALISM High Risk
0 Days
78
133
30 Days
72
126
6m
64
115
1yr
58
53
22
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Core Lab MR Grade at 1 Year (matched)
EVEREST II and Continued Access High Surgical Risk Patients
Continued Access
High Surgical Risk Patients
(n=69 matched cases)
EVEREST II
High Surgical Risk Patients
(n=54 matched cases)
p < 0.0001
p < 0.0001
100
100
2+
0+
Percent Patients
2+
80
1+
3+
60
78%
2+
40
20
4+
3+
4+
0
Baseline
1+
80
1 Year
60
2+
40
20
0
83%
3+
3+
4+
Baseline
4+
1 Year
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EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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LV End Diastolic and Systolic Volumes
EVEREST II and Continued Access High Surgical Risk Patients
Continued Access
High Surgical Risk Patients
(n=63 matched cases)
EVEREST II
High Surgical Risk Patients
(n=54 matched cases)
Baseline
Volume (mL)
200
p < 0.0001
1 Year
Baseline
p = 0.0012
160
120
p = 0.0003
p = 0.011
160
172
120
140
80
158
143
80
82
40
0
200
1 Year
72
Baseline 1 year
Baseline 1 year
LVEDV
LVESV
89
40
0
80
Baseline 1 year
Baseline 1 year
LVEDV
LVESV
24
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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NYHA Functional Class at 1 Year
EVEREST II and Continued Access High Surgical Risk Patients
EVEREST II
High Surgical Risk Patients
(n=54 matched cases)
Continued Access
High Surgical Risk Patients
(n=89 matched cases)
P < 0.0001
P < 0.0001
Percent Patients
100
100
II
I
80
60
III
60
II
40
20
0
74%
80
I
II
III
20
IV
IV
0
Baseline
1 Year
84%
II
40
III
I
IV
III
IV
Baseline
1 Year
25
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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SF-36 Quality of Life Scores at 1 Year
EVEREST II and Continued Access High Surgical Risk Patients
Baseline
80
Mean Score
70
1 Year
Physical Component
Mental Component
80
p < 0.05
p < 0.001
70
60
60
50
50
40
32.1
36.1
33.3
38.7
30
20
20
10
10
Baseline 1 year
EVEREST II HR
n=47 matched
Baseline 1 year
Continued Access HR
n=70 matched
45.5
48.7
p < 0.0001
51.2
43.6
40
30
0
p < 0.06
0
Baseline 1 year
EVEREST II HR
n=47 matched
Baseline 1 year
Continued Access HR
n=70 matched
26
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Hospitalization for CHF
Annual Rate of CHF Rehop*
EVEREST II and Continued Access High Surgical Risk Patients
1
1 Year Prior to MitraClip
1 Year Post MitraClip
EVEREST II
High Surgical Risk Patients
Continued Access
High Surgical Risk Patients
1
p=0.02
0.8
0.6
0.8
0.6
45%
Reduction
0.4
0.65
0.4
p=0.0002
0.86
48%
Reduction
0.45
0.36
0.2
0.2
0
1 Year Prior 1 Year Post
N=75
N=78
0
1 Year Prior 1 Year Post
N=128
N=133
*CHF hospitalizations per patient-year
27
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Summary
 Results consistent with previously demonstrated data in
high surgical risk patients
• MitraClip procedure safe
• MitraClip device provides significant MR reduction and clinical benefits
– LV function, NYHA Function Class and Quality of Life (SF-36)
 Procedural safety improved with increased experience
• Significantly decreased procedure time with comparable effectiveness
• Significantly decreased post-procedure ICU time and hospital stay
• Decreased 30-day mortality
28
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
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Conclusion
 The MitraClip procedure provides
significant clinical benefits in select
patients with significant MR who are at
high risk for surgical mortality.
29
EVEREST II and Continued Access High Surgical Risk – SCAI 2011
Investigational Device only in the U.S. Not available for sale in the U.S.