EVEREST II REALISM - A Continued Access Study To

Report
EVEREST II REALISM - A Continued Access
Study To Evaluate The Safety And
Effectiveness Of The MitraClip® Device:
Demographics And Procedural Outcomes
Laura Mauri, M.D., M.Sc.
On behalf of the EVEREST II REALISM investigators
1
Disclosures - Laura Mauri, M.D., M.Sc.
• Research grants from Abbott, Boston Scientific, Cordis,
Medtronic, Eli Lilly, Daiichi Sankyo, Bristol-Myers Squibb,
Biotronik, and Sanofi-Aventis
• Consulting Medtronic, Eli Lilly, Biotronik, ReCor, St. Jude
2
Transcatheter Mitral Valve Repair
MitraClip® System
All drawings are artist's representations only and should not be considered as an engineering drawing or photograph.
3
MitraClip Therapy
Worldwide Experience
• More than 20,000 patients have been treated with the
MitraClip device worldwide
• In 2008, MitraClip received CE mark for reconstruction of
the insufficient MV through tissue approximation
• In 2013, FDA approved MitraClip for treating significant
symptomatic degenerative mitral regurgitation (DMR) in
patients who have been determined to be at prohibitive
risk for MV surgery by a heart team
Data as of February 6, 2015. Source: Abbott Vascular
4
EVEREST II REALISM
Study Organization
REALISM Trial
A Continued Access Registry of the Evalve® MitraClip® System:
EVEREST II Real World ExpAnded MuLtIcenter Study of the MitraClip System (REALISM)
Principal
Investigators
Ted Feldman, MD
Evanston Northshore University HealthSystem
Data Coordinating
Center
Clinical Events
Committee
Echocardiography
Core Lab
Enrolling Sites
Sponsor
Donald Glower, MD
Duke University Medical Center
NAMSA (formerly Alquest, Inc.)
John Giacomini MD, Jason Lee MD and Neil Schwartz MD
Stanford Hospital and Clinics
Elyse Foster, MD
University of California, San Francisco
Neil J. Weissman, MD
MedStar Health Research Institute
38 North American EVEREST II sites
Enrollment from 2009 to 2013
Abbott Vascular
5
EVEREST II REALISM Enrollment
Site
Principal Investigator
Evanston Hospital, IL
Cedars-Sinai Medical Center, CA
University of Virginia, VA
Terrebonne General Medical Center, LA
Baptist Hospital of Miami, FL
Intermountain Medical Center, UT
St. Luke's Medical Center, WI
Carolina's Medical Center (Sanger Clinic), NC
Baylor University Medical Center, TX
Memorial Hermann Hospital, TX
Piedmont Hospital, GA
El Camino Hospital, CA
The Care Group Medical Center (St. Vincent Hospital), IN
Cleveland Clinic Foundation, OH
Maine Medical Center, ME
Columbia University Medical Center, NY
Oklahoma Heart Hospital, OK
Morristown Memorial Hospital, NJ
Rush University Medical Center, IL
William Beaumont Hospital, MI
Duke University Medical Center, NC
UC Davis Medical Center, CA
University of Colorado Health Sciences Center, CO
Lenox Hill Hospital, NY
Hospital of the University of Pennsylvania, PA
NYU Medical Center, NY
East Carolina Heart Institute
Minneapolis Heart Institute, MN
St. Patrick's Hospital & Health Science Center, MT
St Joseph’s Hospital, Atlanta
Washington Hospital Center, Washington DC
St. Francis Hospital, NY
Washington University School of Medicine, MO
New York Presbyterian Hospital, NY
Medical University of South Carolina
Swedish Medical Center, WA
University of Texas Health Science Center, TX
Shawnee Mission Medical Center, KS
Total
Ted Feldman, MD
Saibal Kar, MD
David Scott Lim, MD
Peter Fail, MD
Ramon Quesada, MD
Brian Whisenant, MD
Tanvir Bajwa, MD
Michael Rinaldi, MD
Paul Grayburn, MD
Richard Smalling, MD
Vivek Rajagopal, MD
Chad Rammohan, MD
James Hermiller, MD
Patrick Whitlow, MD
Mirle Kellett, Jr., MD
William Gray, MD
Robert Kipperman, MD / John Williams, MD
Robert Kipperman, MD
Clifford Kavinsky, MD
George Hanzel, MD
Andrew Wang, MD
Reginald Low, MD
John Carroll, MD
Carlos E. Ruiz, MD, PhD
Howard Herrmann, MD
James Slater, MD
Ramesh Dagubatti, MD / Curtis Anderson, MD
Wesley Pedersen, MD
Mark Sanz, MD / J. Tod Maddux, MD
Louis I. Heller, MD
Lowell Satler, MD
Andrew Berke, MD
John Lasala, MD
S. Chiu Wong, MD
Daniel H. Steinberg, MD
Paul Huang, MD
Steven R. Bailey, MD
Paul Kramer, MD
High Risk Arm
(N=628)
16
77
70
22
32
19
26
18
24
13
21
12
17
23
16
13
12
14
16
17
14
13
10
8
7
8
15
10
12
11
11
7
5
5
4
5
2
3
628
Non-High Risk Arm
(N=271)
9
50
26
14
3
15
6
11
5
15
6
15
9
0
5
7
8
6
4
2
3
4
6
8
8
7
0
4
1
1
0
3
3
3
2
0
2
0
271
Total
(N=899)
25
127
96
36
35
34
32
29
29
28
27
27
26
23
21
20
20
20
20
19
17
17
16
16
15
15
15
14
13
12
11
10
8
8
6
5
4
3
899
6
Background
EVEREST II REALISM is a prospective, multi-center, continued access study designed
for continued “real world” data collection originally in support
of the US PMA application for the MitraClip device
High Risk Arm
The High Risk (HR) arm enrolled patients considered HR for mitral valve
(MV) surgery based on either a predicted procedural Society of
Thoracic Surgeons (STS) mortality of ≥12% or based on the presence of
certain pre-specified surgical risk factors.
Non-High Risk
Arm
The Non-High Risk (NHR) arm enrolled standard-risk patients.
7
Purpose and Methods
Purpose
Methods
1 Zoghbi
•
To present baseline demographics, clinical and acute procedural data
results of the High Risk and Non-High Risk arms of EVEREST II REALISM
•
•
Patients were first screened for HR status
Patients with moderate-to-severe (3+) or severe (4+) mitral
regurgitation (MR), as determined by the site from a transthoracic
echocardiogram (TTE), were considered for enrollment in this study.
Clinical measures were assessed at baseline and 30 days
– MR severity and LV size by Echo Core Lab using ASE guidelines1
– NYHA Functional Class
– SF-36 Quality of Life
•
et al. J Am Soc Echocardiogr 2003;16:777-802
8
Key Inclusion/Exclusion Criteria
REALISM High Risk
Inclusion
• Symptomatic moderate to severe
(3+) or severe (4+) chronic MR
• Primary regurgitant jet originates
from leaflet mal-coaptation at
A2/P2 region
• Predicted surgical mortality risk
≥12%
– STS calculated or
– Determined by cardiothoracic
surgeon based on pre-defined
risk factors
Exclusion
•
•
•
•
AMI within 12 weeks
Endocarditis
Rheumatic heart disease
MV anatomical exclusions
– Mitral valve area <4.0 cm2
– Leaflet flail width (≥15 mm) and
gap (≥10mm)
– Leaflet tethering with
coaptation length (<2 mm)
• LVEF <20% and/or LVESD >60mm
Bonow et al. 2008 Focused Update Incorporated Into ACC/AHA 2006 Guidelines (Writing
Committee to Revise 1998 Guidelines). JACC 2008;52:e1-e142
9
Key Inclusion/Exclusion Criteria
REALISM Non-High Risk
Inclusion
• Moderate to severe (3+) or severe (4+)
chronic MR
– Symptomatic with LVEF >25% and LVESD
≤55 mm
– Asymptomatic with one or more of the
following:
•
•
•
•
LVEF 25-60%
LVESD ≥40 mm
New onset of atrial fibrillation
PASP >50 mmHg at rest or >60 mmHg with
exercise
• Primary regurgitant jet originates from
leaflet mal-coaptation at A2/P2 region
• Candidate for MV Surgery
Exclusion
•
•
•
•
AMI within 12 weeks
Endocarditis
Rheumatic heart disease
MV anatomical exclusions
– Mitral valve area <4.0 cm2
– Leaflet flail width (≥15 mm) and gap
(≥10mm)
– Leaflet tethering with coaptation length
(<2 mm)
• Need for other cardiac surgery
• Renal insufficiency
– Creatinine >2.5mg/dl
• LVEF <25% and/or LVESD >60mm
Bonow et al. 2008 Focused Update Incorporated Into ACC/AHA 2006 Guidelines (Writing
Committee to Revise 1998 Guidelines). JACC 2008;52:e1-e142
10
Clinical Follow-Up
EVEREST II REALISM
EVEREST II REALISM
N=965
Enrolled
Jan 2009 - Dec 2013
High Risk Arm
N=628
Compassionate and
Emergency Use
N=66
Non-High Risk Arm
N=271
Withdrew 5
Missing 10
Withdrew 4
Missing
5
High Risk Arm
30-Day Analysis
N=613
(98% Clinical Follow-Up)
Non-High Risk Arm
30-Day Analysis
N=262
(97% Clinical Follow-Up)
Enrolled
Jan 2009 – Apr 2011
Through data cut-off of February 7, 2015
11
Baseline Demographics and Co-Morbidities
EVEREST II REALISM
Characteristics
Age (mean ± SD)
Over 75 years of age
Male
NYHA Functional Class III/IV
Congestive Heart Failure
Coronary Artery Disease
Prior Myocardial Infarction
Previous CABG
Atrial Fibrillation
Chronic Obstructive Pulmonary Disease
Diabetes
Moderate to Severe Renal Disease
Cerebrovascular Disease
STS Mortality Risk Score (mean ± SD)
EVEREST II REALISM
High-Risk Arm
Non-High Risk Arm
(N=628)
(N=271)
77 ± 11 years
74 ± 11 years
63%
60%
85%
98%
78%
48%
54%
71%
32%
36%
30%
24%
11.1 ± 7.0%
52%
53%
54%
82%
49%
19%
17%
56%
22%
19%
9%
13%
12
Baseline Echocardiographic Parameters
EVEREST II REALISM
Characteristics
Echo Core Lab Assessed MR ≥3+, (%)
Functional MR Etiology
Degenerative MR Etiology
LV Ejection Fraction (mean ± SD)
LV End Diastolic Volume (mean ± SD)
LV End Systolic Volume (mean ± SD)
LV End Diastolic Dimension (mean ± SD)
LV End Systolic Dimension (mean ± SD)
EVEREST II REALISM
High-Risk Arm
Non-High Risk Arm
(N=628)
(N=271)
81%
88%
70%
32%
30%
68%
47 ± 14%
151 ± 55 ml
84 ± 45 ml
5.6 ±0.8 cm
4.4 ± 1.1 cm
56 ± 11%
131 ± 43 ml
59 ± 30 ml
5.3 ± 0.7 cm
3.7 ± 0.9 cm
13
MitraClip Therapy
Worldwide Commercial Implant Experience
Etiology
>20,000 Patients
Mixed 13%
DMR 22%
FMR 65%
Implant Rate: 96%
Data as of February 6, 2015. Source: Abbott Vascular
14
Implant Rate
High Risk Arm
N=628
Non-High Risk Arm
N=271
96.0% Implant Rate
95.2% Implant Rate
15
Procedural and Post-Procedural Results
Procedural and Post-Procedural Results
EVEREST II REALISM
High-Risk Arm
Non-High Risk Arm
(N=628)
(N=271)
Procedural (mean ± SD)
Procedure time
Device time
Fluoroscopy duration
139 ± 67 min
107 ± 58 min
39 ± 24 min
138 ± 68 min
112 ± 64 min
35 ± 20 min
Post-Procedural (mean ± SD)
ICU/CCU duration
Length of hospital stay
1.5 ± 2.9 days
3.2 ± 4.6 days
1.2 ± 2.9 days
2.8 ± 4.8 days
16
Discharge Location
Discharge Location
Home
Without home healthcare
With home healthcare
Skilled Nursing Facility
Nursing Home
Long Term Acute Care
Died Prior to Discharge
EVEREST II REALISM
High-Risk Arm
Non-High Risk Arm
(N=628)
(N=271)
90.1%
96.3%
83.3%
6.8%
5.4%
2.4%
0.0%
1.9%
91.5%
4.8%
1.1%
1.1%
0.4%
0.7%
17
Major Adverse Events at 30 Days
CEC Adjudicated
Description of Event
EVEREST II REALISM
High-Risk Arm
Non-High Risk Arm
(N=628)
(N=271)
Death
4.1%
1.5%
Myocardial infarction
0.5%
0.0%
Re-operation for failed surgical repair or replacement
0.0%
0.4%
Non-elective cardiovascular surgery for adverse events
1.3%
2.2%
Stroke
1.9%
2.2%
Renal Failure
1.1%
0.7%
Deep wound infection
0.0%
0.0%
Ventilation > 48 hours
3.3%
2.2%
GI complication requiring surgery
0.0%
0.0%
New onset of permanent AF
0.2%
0.0%
Septicemia
1.3%
1.1%
Transfusion ≥ 2 units
11.3%
7.7%
Total
15.4%
11.4%
Total number of patients may not equal the sum of patients in each row since one patient may experience multiple events.
18
Device Safety Results Through 30 Days
Description of Event
Single Leaflet Device Attachment (SLDA)
MV stenosis
EVEREST II REALISM
High-Risk Arm
Non-High Risk Arm
(N=628)
(N=271)
2.2%
3.5%
0.8%
0.8%
0
0
Mitral Valve Surgery Within 30 Days
1.6%
4.1%
Second Intervention to Place an Additional
MitraClip Device Within 30 Days
0.3%
0.7%
Device Embolization
19
Mitral Regurgitation Severity
Echo Core Lab Assessed
High Risk Arm
N=628
Non-High Risk Arm
N=271
p < 0.0001
p < 0.0001
12%
19%
89%
90%
Paired Data (N=532)
Paired Data (N=259)
N=survivors with paired data at 30 days or hospital discharge, whichever is longer post-procedure; p-values for descriptive purposes only
20
NYHA Functional Class
High Risk Arm
N=628
Non-High Risk Arm
N=271
p < 0.0001
p < 0.0001
15%
46%
82%
Paired Data (N=560)
89%
Paired Data (N=252)
N=survivors with paired data at 30 days; p-values for descriptive purposes only
21
Change in LV Volumes and Dimensions From Baseline
Echo Core Lab Assessed
REALISM High Risk
REALISM Non-High Risk
LVEDV (ml)
LVIDd (cm)
-9.2 [-11.6, -6.7]
-0.17 [-0.20, -0.13]
N=472; p<0.0001
N=523; p<0.0001
N=227; p<0.0001
N=255; p<0.0001
-10.0 [-12.6, -7.3]
-0.18 [-0.22, -0.13]
LVESV (ml)
LVIDs (cm)
-1.5 [-3.5, 0.52]
-0.07 [-0.11, -0.03]
N=471; p=0.2
N=500; p=0.0009
N=227; p=0.9
N=240; p=0.3
0.10 [-1.39, 1.59]
-0.03 [-0.09, 0.03]
N=survivors with paired data at 30 days or hospital discharge, whichever is longer post-procedure; p-values for descriptive purposes only
22
SF-36 Quality of Life
EVEREST II REALISM
High Risk Arm
N=628
Non-High Risk Arm
N=271
 = 4.3 points
p < 0.0001
 = 5.1 points
p < 0.0001
 = 5.7 points
p < 0.0001
Paired Data (N=499)
 = 4.5 points
p < 0.0001
Paired Data (N=93)
N=survivors with paired data at 30 days; p-values for descriptive purposes only
PCS = Physical Component Score; MCS = Mental Component Score
23
Summary
• The High Risk Arm of EVEREST II REALISM enrolled patients with more
advanced age, more co-morbid conditions, and more frequent presence
of functional MR than patients enrolled in the Non-High Risk Arm.
• Despite baseline differences in risk status, US real world experience in
both High Risk and Non-High Risk patients shows the MitraClip
procedure
– Can be performed consistently with a high device implant rate (>95%)
– Involves a short hospital stay (3 days)
– Allows a large majority (90%) of patients to be discharged home
• Totality of procedural and 30-day data suggest improved functional and
clinical outcomes
–
–
–
–
MR reduction to ≤ 2+ in 89% of patients
Improvements in NYHA Functional Class (84% Class I/II at 30 days)
Reduction in LV dimensions and volumes
Improvements in SF-36 Quality of Life measures
24
Limitations
• While these results shed light on outcomes between different types of
patients treated with the MitraClip device for varying etiologies of
mitral regurgitation, with and without increased surgical risk,
• Analyses presented are
– descriptive in nature and exploratory
– not prospectively designed to detect differences in outcomes
between High Risk and Non-High Risk arms
25
Conclusion
• In real-world continued access use in the US, the MitraClip procedure
provides meaningful clinical benefits in select patients
• Results in EVEREST II REALISM are consistent
– In both high risk and standard risk patients
– In FMR and DMR
• EVEREST II REALISM reflects how the MitraClip therapy has been
adopted in patients with high surgical risk (70% with FMR), similar to
global patterns of use where use in FMR predominates (65%).
26

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