1. Final Results of the EVEREST II Randomized Controlled Trial of Percutaneous and Surgical Reduction of Mitral Regurgitation
Ted Feldman, MD, FACC, FESC, FSCAI on behalf of the EVEREST II Investigators
ACC 2014
Washington, DC
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2. Ted Feldman MD, FACC, FESC, FSCAI
Disclosure Information The following relationships exist: Grant support: Abbott, BSC, Edwards, WL Gore Consultant: Abbott, BSC, Coherex, Edwards, Intervalve,
Diiachi Sankyo-Lilly, WL Gore
Off-label use of products and investigational devices will be discussed in this presentation
The EVEREST II RCT was funded by Abbott Vascular
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3. EVEREST II RCT Clinical Investigators
T Feldman, J Alexander, R Curran, E Chedrawy, S Smart, M Lampert NorthShore University HealthSystem, Evanston, IL
A Wang, D Glower, J Jollis Duke University, Durham, NC
T Byrne, P Tibi, HK Fang, JM Morgan Banner Good Samaritan Medical Center, Phoenix, AZ
R Quesada, J Lamelas, N Moreno, R Machado Baptist Hospital of Miami, Miami, FL
P Grayburn, B Hamman, R Hebeler, M Mack, W Ryan Baylor University Medical Center, Dallas, TX
A Eisenhauer, M Davidson, L Cohn, J Wu Brigham and Women’s Hospital, Boston, MA
J Hermiller, D Heimansohn, K Allen, D Segar The Care Group, Indianapolis, IN
M Rinaldi, E Skipper, R Steigel, J Cook, G Rose Carolinas Medical Center, Charlotte, NC
S Kar, R Makkar, G Fontana, A Trento, R Kass, W Cheng, R Siegel, K Tolstrup Cedars-Sinai Medical Center, Los Angeles, CA
P Whitlow, T Mihaljevic, N Smidera, L Svensson, E Roselli, L Rodriquez, W Stewart The Cleveland Clinic, Cleveland, OH
H Wasserman, W Gray, A Stewart, M Williams, M Argenziano, S Homma, R Pizzarello, L Gillam Columbia University, New York, NY; Danville, CT
P Block, Z Ghazzal, T Vassiliades, R Martin, J Merlino, S Lerakis Emory University Hospital, Atlanta, GA
B Whisenant, S Clayson, B Reid, S Horton, J Orford Latter Day Saints Hospital, Salt Lake City, UT
R Smalling, G Letsou, J Walkes, C Loghin Memorial Hermann Hospital, Houston, TX
W Pedersen, V Kshettry, F Eales, T Flavin, T Kroshus, R Bae Minneapolis Heart Institute, Minneapolis, MN
O Nass, D Gangahar, R Jex, R Kacere Nebraska Heart Institute, Lincoln, NE
SC Wong, OW Isom, L Girardi, K Krieger, R Devereux, R Mishra New York Presbyterian Hospital, New York, NY
J Slater, A Galloway, G Perk, I Kronzon NYU Medical Center, New York, NY
S Ramee, C Van Meter, P Parrino, C Lavie, Y Gilliland, VS Lucas Ochsner Clinic Foundation, New Orleans, LA
R Kipperman, S Lucas, RM Bodenhamer, J Randolph, J Williams Oklahoma Heart Hospital, Okalahoma City, OK
R Leung, R MacArthur, J Mullen, D Ross, J Choy Royal Alexandra Hospital, Edmonton, AB, Canada
P Kramer, B Castlemain, A Schwartz, L Crouse, V Pasnoori Shawnee Mission Medical Center, Shawnee Mission, KS
A Berke, N Robinson, R Colangelo, P Damus, H Fernandez, J Taylor, N Bercow, A Katz St. Francis Hospital, Long Island, NY
M O'Donnell, M Qureshi, A Pruitt, B Kong, B McAllister, S Girard St. Joseph’s Mercy Hospital, Ypsilanti, MI
T Bajwa, D O’Hair, D Kress, K Sagar St. Luke’s Medical Center, Milwaukee, WI
JT Maddux, M Sanz, S Tahta, JM Maxwell, B Berry, J Knapp St. Patrick's Hospital & Health Science Ctr, Missoula, MT
W Gray, M Reisman, W Curtis, D Gartman, J Teply, D Warth, K Krabill Swedish Medical Center, Seattle, WA
P Fail, K Paape, T Fudge, M Trotter, M Allam, E Feinberg, V Tedesco, D Solet Terrebonne General Medical Center, Houma, LA
E Horlick, T David, M Borger, M Mezody Toronto General Hospital, Toronto, ON, Canada
R Low, N Young, K Shankar, R Calhoun, W Bommer University of California at Davis, Sacramento, CA
J Carroll, J Cleveland, R Quaife University of Colorado Health Sciences Center, Denver, CO
H Herrmann, M Acker, YJ Woo, F Silvestry, S Wiegers University of Pennsylvania, Philadelphia, PA
S Bailey, E Sako, J Erikson University of Texas Health Sciences Ctr, San Antonio, TX
DS Lim, I Kron, J Kern, J Dent, H Gutgesell University of Virginia, Charlottesville, VA
E Fretz, J Ofiesh, M Mann Victoria Heart Institute Foundation, Victoria BC, Canada
K Kent, S Boyce, P Sears-Rogan Washington Hospital Center, Washington DC
J Lasala, M Moon, R Damiano, B Lindman, A Zajarias, J Madrazo Washington University Medical Center, St. Louis, MO
G Hanzel, F Shannon, M Sakwa, A Abbas, M Gallagher, P Markovitz William Beaumont Hospital, Royal Oak, MI
Interventional Cardiologist, Cardiac Surgeon, Echocardiologist
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4. Transcatheter Mitral Valve Repair MitraClip® System
All drawings are artist's representations only and should not be considered as an engineering drawing or photograph.
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5. Background EVEREST II RCT
The EVEREST II RCT was a prospective, multi-center trial designed to compare the safety and effectiveness of the MitraClip System with mitral valve (MV) surgery in the treatment of patients with significant (≥3+) mitral regurgitation (MR)
Five-year follow-up on all patients is complete and the EVEREST II RCT is closed
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6. Background EVEREST II RCT
1Feldman et al. NEJM 2011;364:
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7. Purpose EVEREST II RCT Methods EVEREST II RCT
To present the final 5-year results from the EVEREST II RCT
Methods EVEREST II RCT
MR grade and Left Ventricular (LV) function were assessed by the Echocardiography Core Lab using ASE guidelines2 at baseline and 1 year annually through 5 years
NYHA Functional Class was assessed at baseline and 1 year annually through 5 years
2Zoghbi et al. J Am Soc Echocardiogr 2003;16:
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8. Key Inclusion/Exclusion Criteria EVEREST II RCT
Candidate for MV Surgery
Moderate to severe (3+) or severe (4+) MR
Symptomatic
>25% EF & LVESD ≤55mm
Asymptomatic with one or more of the following
LVEF 25-60%
LVESD ≥40mm
Pulmonary hypertension
Atrial fibrillation
Exclusion
AMI within 12 weeks
Need for other cardiac surgery
Renal insufficiency
Creatinine >2.5mg/dl
Endocarditis
Rheumatic heart disease
MV anatomical exclusions
Mitral valve area <4.0cm2
Leaflet flail width (≥15mm) and gap (≥10mm)
Leaflet tethering/coaptation depth (>11mm) and length (<2mm)
ACC/AHA 2008 Guidelines: Bonow et al JACC 2008;52:e1-e142
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9. Baseline Characteristics EVEREST II RCT
MitraClip N = 184
Surgery N = 95
p-value
Age (mean), years 67 66 ns
Male
63%
66%
History of CHF
91%
78%
0.005
NYHA Functional Class III/IV
51%
47%
Functional MR Etiology
26%
27%
Coronary Artery Disease
46%
Prior Myocardial Infarction
22%
21%
Previous Cardiovascular Surgery
19%
Atrial Fibrillation
34%
39%
COPD (with or without home O2)
15%
Moderate to Severe Renal Disease 3% 2%
Diabetes 8%
11%
LV Ejection Fraction (mean), % 60 61
LV End Systolic Dimension (mean), cm
3.7
3.5
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10. Clinical Follow-Up EVEREST II RCT
Aug Nov 2008 Randomized Cohort N=279
Treated MitraClip Patients
N=178
Untreated n=6 MitraClip
n=15 Surgery
Treated Surgery Patients
N=80
N=258 Treated Patients
N=30
Withdrawals
N=15
N=3
Missed Visits
N=2
81% Clinical Follow-Up 5-Year Analysis (N=145)
79% Clinical Follow-Up 5-Year Analysis (N=63)
Median follow-up 4.93 years. 1,007 total patient-years of follow-up.
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11. Site-Reported Adverse Events Through 5 Years EVEREST II RCT
AE Categories
Cardiac M
Vascular
Adverse Event Rates (%) Per Patient-Year of Follow-up
Neurologic
Renal
M: MitraClip
S: Surgery M S M S M S M S M S
Index Through 30 Days
30 Days Through 1 Year
1 Year Through
2 Years
2 Years Through
3 Years
3 Years Through
4 Years
4 Years Through
5 Years
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12. Long-Term MitraClip Device Safety EVEREST II RCT
Through 1 Year
# (%) of patients
1 Year to 5 Years
Single Leaflet Device Attachment (SLDA)
10 (6.3%)
0 (0.0%)
MV stenosis
1 (0.6%)
Device Embolization
MV stenosis = as confirmed by the protocol definition (Defined as a mitral valve orifice area of less than 1.5 cm2 as measured by the
Echocardiographic Core Laboratory.)—pg 52 EII protocol rev G.
Based on N=158 who were implanted with 1 or 2 MitraClip devices
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13. Kaplan-Meier Freedom From Mortality
EVEREST II RCT
MitraClip (N=178)
Surgery (N=80)
93.7% 92.3%
1 year
81.2% 79.0%
5 years
Proportion of Patients Surviving
Baseline
6 Months
12 Months
18 Months
2 Years
3 Years
4 Years
5 Years
MitraClip
# At Risk
178
165
158
154
143
133
119 58
Surgery 80 76 70 65 57 52 24
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14. Kaplan-Meier Freedom From MV Surgery in MitraClip Group or Re-operation in Surgery Group
Surgery (N=80)
MitraClip (N=178)
78.9% 97.4%
1 year
74.3% 92.5%
5 years
Proportion of Patients Free From Surgery
Baseline
6 Months
12 Months
18 Months
2 Years
3 Years
4 Years
5 Years
MitraClip
# At Risk
178
136
128
125
117
109 98 45
Surgery 80 75 69 68 63 54 49 21
EVEREST II RCT
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15. Kaplan-Meier Freedom From MV Surgery in MitraClip Group or Re-operation in Surgery Group
97.1% 98.7%
1 year
91.4% 93.7%
5 years
Proportion of Patients Free From Surgery
6-Month Landmark Analysis
EVEREST II RCT
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16. Mitral Regurgitation Grade EVEREST II RCT All Treated Patients (N=258)
MitraClip (N=178)
MR ≤ 2+ at 1 and 5 Years
Surgery (N=80)
MR ≤ 2+ at 1 and 5 Years
p < 0.005
p < 0.005
p < 0.005
p < 0.005
81%
82%
99%
98% 2+ 0+ 2+ 2+ 0+ 0+ 1+ 1+ 3+ 3+ 1+ 3+ 3+ 1+ 2+ 2+ 4+ 3+ 4+ 2+ 3+ 4+ 4+ 2+
Baseline
1 Year
Baseline
5 Years
Baseline
1 Year
Baseline
5 Years
N=149
N=106
N=66
N=41
N = survivors with paired data; p-values for descriptive purposes only
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17. Reduction in LV Volumes at 1 and 5 Years
LVEDV (ml) at 1 Year
LVEDV (ml) at 5 Years
N=144
p<0.0001
N=105
p<0.0001
N=65
p<0.0001
N=40
p<0.0001
Surgery
MitraClip
EII RCT
LVESV (ml) at 1 Year
LVESV (ml) at 5 Years
N=144
p<0.0001
N=105
p<0.01
N=65
p=0.05
N=40
p<0.01
Mean ± SD (ml)
Mean ± SD (ml)
N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes only
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18. Reduction in LV Dimensions at 1 and 5 Years
LVIDd (cm) at 1 Year
LVIDd (cm) at 5 Years
N=148
p<0.0001
N=106
p<0.0001
N=66
p<0.0001
N=42
p<0.0001
Surgery
MitraClip
EII RCT
LVIDs (cm) at 1 Year
LVIDs (cm) at 5 Years
N=146
p=ns
N=104
p=ns
N=66
p=ns
N=42
p=ns
Mean ± SD (cm)
Mean ± SD (cm)
N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes only
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19. NYHA Functional Class EVEREST II RCT All Treated Patients (N=258)
MitraClip (N=178)
NYHA I/II at 1 and 5 Years
Surgery (N=80)
NYHA I/II at 1 and 5 Years
p < 0.005
p < 0.005
p < 0.005
p < 0.005
98%
91%
88%
98% I I I I II I II I I I II II
III
III
III II II
III II II
III IV IV
III IV IV
Baseline
1 Year
Baseline
5 Years
Baseline
1 Year
Baseline
5 Years
N=151
N=106
N=66
N=42
N = survivors with paired data; p-values for descriptive purposes only
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20. Septal Lateral Annular Dimensions EVEREST II RCT All Treated Patients - MitraClip Group (N=178)
MitraClip (N=178)
Systolic SLAD at 1 and 5 Years
MitraClip (N=178)
Diastolic SLAD at 1 and 5 Years
p = ns
p = ns
p < 0.05
p = ns
Mean SLADdiast (cm)
Mean SLADsyst (cm)
Baseline
1 Year
Baseline
5 Years
Baseline
1 Year
Baseline
5 Years
N=124
N=90
N=124
N=90
N = survivors with paired data; p-values for descriptive purposes only
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21. Long-Term Durability of Clinical Success
5-Year Outcomes in Patients Who Were Alive and Free From MR 3+/4+ and MV Surgery (or Re-Operation) at 1 Year
EVEREST II RCT Clinical Success Groups
Outcome
MitraClip (N=97)
Surgery (N=64)
Freedom From Death at 5 Years
87%
90%
Freedom From MV Surgery (or Re-operation) at 5 Years
94%
95%
MR ≤ 2+ at 5 Years
86%
97%
MR ≤ 1+ at 5 Years
47%
92%
NYHA Class III/IV (%) Baseline  5 Years
47%  6%
40%  3%
Mean Change in LVEDV From Baseline to 5 Years
-27 ml
-45 ml
Mean Change in Diastolic SLAD From Baseline to 5 Years
0.0 cm
-0.4 cm
MR, NYHA and LV data are from survivors with paired data; freedom from events data are from Kaplan-Meier estimates
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22. EVEREST II RCT – 5 Year Results Summary
The EVEREST II RCT is the longest prospective follow-up of two therapies for treating MR
Clinical benefits provided by MitraClip and MV surgery are durable through 5 years
Reduction in MR Severity
Improvement in LV Volumes and Dimensions
Improvements in NYHA Functional Class
Low rate of adverse events from 1 year to 5 years in both groups
Beyond 6 months, the rate of MV surgery is low in the MitraClip group
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23. EVEREST II RCT – 5 Year Results Conclusions
MitraClip procedure outcomes are durable through 5 years
For select patients with significant MR, the MitraClip procedure is a therapeutic option with measureable clinical benefits and no late safety concerns
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24. Abbott Vascular
4045 Campbell Avenue, Menlo Park, CA USA, Tel:
EVEREST II is an Abbott Vascular Sponsored Clinical Trial.
Caution: This product is intended for use by or under the direction of a physician. Prior to use, reference the Instructions for Use at for more detailed information on Indications, Contraindications, Warnings, Precautions and Adverse Events.
All drawings are artist's representations only and should not be considered as an engineering drawing or
photograph. MitraClip is a trademark of the Abbott Group of Companies.
©2014 Abbott. All rights reserved. PML04247 Rev. A