E ndovascular V alve E dge-to- Edge RE pair St udy (EVEREST II) Randomized Clinical Trial: Primary Safety and Efficacy Endpoints American College of Cardiology March 14, 2010 Atlanta, GA Ted Feldman, Laura Mauri, Elyse Foster, Don Glower on behalf of the EVEREST II Investigators
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Endovascular Valve Edge-to-Edge REpair Study (EVEREST II) Randomized Clinical Trial: Primary Safety and Efficacy Endpoints American College of Cardiology.
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Endovascular Valve Edge-to-Edge REpair Study (EVEREST II)Randomized Clinical Trial: Primary Safety and Efficacy
Endpoints
American College of CardiologyMarch 14, 2010
Atlanta, GA
Ted Feldman, Laura Mauri, Elyse Foster, Don Glower on behalf of the EVEREST II Investigators
2Investigational Device only in the US; Not available for sale in the US
Disclosures
Research Grants – Abbott, Edwards
Consultant – Abbott, Edwards
3Investigational Device only in the US; Not available for sale in the US
Perspective
>250,000 cases of significant Mitral Regurgitation diagnosed annually in the US
Current therapeutic options:• Medical management
– Effective in symptom management – Ineffective in treating underlying pathophysiology or
disease progression• Surgical Repair or Replacement (Standard of Care)
– Effective yet invasive with associated morbidity– Only ~20% of patients with significant MR undergo MV
surgery
Unmet need for an effective less invasive option
4Investigational Device only in the US; Not available for sale in the US
Catheter-Based Mitral Valve Repair
MitraClip® System
5Investigational Device only in the US; Not available for sale in the US
Clinical Experience
Study Population n
EVEREST I (Feasibility)* Non-randomized 55
EVEREST II* Pre-randomization 60
EVEREST II High Risk Registry 78
EVEREST II (Pivotal) Randomized patients(2:1 MitraClip to Surgery)
279184 MitraClip95 Surgery
REALISM (Continued Access)
High Risk & Non High Risk
266
European Experience 472
Total 1,115 MitraClip
Data as of 2/15/2010.
*Percutaneous Mitral Valve Repair Using the Edge-to-Edge Repair: Six months Results of the EVEREST Phase I Clinical trial, JACC 2005;46:2134-2140. Percutaneous Mitral Repair with the MitraClip System: Safety and Midterm Durability in the Initial EVEREST Cohort, JACC 2009; 54:686-694.
6Investigational Device only in the US; Not available for sale in the US
EVEREST II Randomized Clinical Trial
Study Design279 Patients enrolled at 37 sites
Randomized 2:1
Echocardiography Core Lab and Clinical Follow-Up:
Baseline, 30 days, 6 months, 1 year, 18 months, and annually through 5 years
7Investigational Device only in the US; Not available for sale in the US
EVEREST II Randomized Clinical TrialStudy Organization
Principal Investigators: Ted Feldman, MD Evanston NorthShore University HealthSystem
Donald Glower, MD Duke University Medical Center
Academic Research Organization: Laura Mauri, MD Harvard Clinical Research Institute
Data Safety Monitoring Board: Richard Shemin, MDUniversity of California, Los Angeles
Clinical Events Committee: Don Cutlip, MDHarvard Clinical Research Institute
Echocardiography Core Lab: Elyse Foster, MD University of California, San Francisco
Sponsor: Abbott Vascular Structural Heart (Evalve)Menlo Park, CA
8Investigational Device only in the US; Not available for sale in the US
EVEREST Clinical InvestigatorsT Feldman, J Alexander, R Curran, E Chedrawy, S Smart, M Lampert NorthShore University HealthSystem, Evanston, ILA Wang, D Glower, J Jollis Duke University, Durham, NCT Byrne, P Tibi, HK Fang, JM Morgan Banner Good Samaritan Medical Center, Phoenix, AZR Quesada, J Lamelas, N Moreno, R Machado Baptist Hospital of Miami, Miami, FLP Grayburn, B Hamman, R Hebeler, M Mack, W Ryan Baylor University Medical Center, Dallas, TXA Eisenhauer, M Davidson, L Cohn, J Wu Brigham and Women’s Hospital, Boston, MAJ Hermiller, D Heimansohn, K Allen, D Segar The Care Group, Indianapolis, INM Rinaldi, E Skipper, R Steigel, J Cook, G Rose Carolinas Medical Center, Charlotte, NCS Kar, G Fontana, A Trento, R Kass, W Cheng, R Siegel, K Tolstrup Cedars-Sinai Medical Center, Los Angeles, CAP Whitlow, T Mihaljevic, N Smidera, L Sevensson, E Roselli, L Rodriquez, W Stewart The Cleveland Clinic, Cleveland, OHH Wasserman, W Gray, A Stewart, M Williams, M Argenziano, S Homma, R Pizzarello, L Gillam Columbia University, New York, NY; Danville, CTP Block, Z Ghazzal, T Vassiliades, R Martin, J Merlino, S Lerakis Emory University Hospital, Atlanta, GAB Whisenant, S Clayson, B Reid, S Horton, J Orford Latter Day Saints Hospital, Salt Lake City, UTR Smalling, G Letsou, J Walkes, C Loghin Memorial Hermann Hospital, Houston, TXW Pedersen, V Kshettry, F Eales, T Flavin, T Kroshus, R Bae Minneapolis Heart Institute, Minneapolis, MNO Nass, D Gangahar, R Jex, R Kacere Nebraska Heart Institute, Lincoln, NESC Wong, OW Isom, L Girardi, K Krieger, R Devereux, R Mishra New York Presbyterian Hospital, New York, NYJ Slater, A Galloway, G Perk, I Kronzon NYU Medical Center, New York, NYS Ramee, C Van Meter, P Parrino, C Lavie, Y Gilliland, VS Lucas Ochsner Clinic Foundation, New Orleans, LAR Kipperman, S Lucas, RM Bodenhamer, J Randolph, J Williams Oklahoma Heart Hospital, Okalahoma City, OKR Leung, R MacArthur, J Mullen, D Ross, J Choy Royal Alexandra Hospital, Edmonton, AB, CanadaP Kramer, B Castlemain, A Schwartz, L Crouse, V Pasnoori Shawnee Mission Medical Center, Shawnee Mission, KSA Berke, N Robinson, R Colangelo, P Damus, H Fernandez, J Taylor, N Bercow, A KatzSt. Francis Hospital, Long Island, NYM O'Donnell, M Qureshi, A Pruitt, B Kong, B McAllister, S Girard St. Joseph’s Mercy Hospital, Ypsilanti, MIT Bajwa, D O’Hair, D Kress, K Sagar St. Luke’s Medical Center, Milwaukee, WIJT Maddux, M Sanz, S Tahta, JM Maxwell, B Berry, J Knapp St. Patrick's Hospital & Health Science Ctr, Missoula, MTW 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, LAE Horlick, T David, M Borger, M Mezody Toronto General Hospital, Toronto, ON, CanadaR Low, N Young, K Shankar, R Calhoun, W Bommer University of California at Davis, Sacramento, CAJ Carroll, J Cleveland, R Quaife University of Colorado Health Sciences Center, Denver,
COH 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, TXDS Lim, I Kron, J Kern, J Dent, H Gutgesell University of Virginia, Charlottesville, VAE Fretz, J Ofiesh, M Mann Victoria Heart Institute Foundation, Victoria BC, Canada K Kent, S Boyce. P Sears-Rogan Washington Hospital Center, Washington DCJ 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
EVEREST II Randomized Clinical TrialBaseline Demographics & Co-morbidities
11Investigational Device only in the US; Not available for sale in the US
EVEREST II RCT
n=279
2008 STS Database
Isolated 1st Elective Operation for MR*
Repair Replace High Volume Hospitals (>140/Yr)
Age yrs (mean) 68 60 61 59
≥65 yrs 58% 37% 45% n/a
≥75 yrs 32% n/a n/a 0%
NYHA Class III or IV 50% 26% 45% n/a
CHF 86% 41% 58% n/a
Hypertension 75% 60% 67% 43%
Diabetes Mellitus 9% 13% 23% 6.5%
COPD / Chronic Lung Disease
15% 17% 29% n/a
EF (mean) 60% 53% 55% 56%
EVEREST II Randomized Clinical TrialDemographic Comparison
*Gammie JS et al Influence of Hospital Procedural Volume on Care Process and Mortality for Patients Undergoing Elective Surgery for Mitral Regurgitation. Circ 2007;115:881-887.
12Investigational Device only in the US; Not available for sale in the US
EVEREST II Randomized Clinical TrialPrimary Endpoints
Safety Major Adverse Event Rate at 30 days Per protocol cohort Superiority hypothesis
Effectiveness Clinical Success Rate
• Freedom from the combined outcome of– Death – MV surgery or re-operation for MV dysfunction– MR >2+ at 12 months
13Investigational Device only in the US; Not available for sale in the US
EVEREST II Randomized Clinical TrialAdditional Analyses
Intention to Treat Safety
• Major Adverse Event Rate at 30 days Effectiveness
• Freedom from the combined outcome of death, MV surgery >90 days or re-operation for valve dysfunction >90 days post Index procedure, and MR >2+ at 12 months
Clinical Benefit (per protocol cohort) MR Severity Left Ventricular Function NYHA Functional Class Quality of Life (SF-36 Survey)
14Investigational Device only in the US; Not available for sale in the US
EVEREST II RCT: Patient FlowPer Protocol Cohort: Analysis of Device
Performance
Acute Procedural Success (APS) = MR ≤2+ at
discharge
12 months n=134
98.5% Clinical Follow-up
98% Echo Follow-up
12 months n=74
94% Clinical Follow-up92% Echo Follow-up
30 daysn=136
99% Clinical Follow-up
30 daysn=79
99% Clinical Follow-up
Acute Procedural SuccessAchievedn=137
Randomized, not treated
Device, n=6Control, n=15
Treated n=178
Treated n=80
(86% MV repair)
Device Group n=184
Acute Procedural SuccessNot Achieved
n=41
Control Group n=95
Randomized Cohort n=279
15Investigational Device only in the US; Not available for sale in the US
EVEREST II RCT: Patient FlowPost MitraClip Procedure
2nd MitraClipProcedure
n=3
MV Surgery PostMitraClip
Proceduren=9
2nd MitraClip Procedure
n=2
No Additional Intervention
n=11
MV Surgery Post MitraClip
Proceduren=28
Acute Procedural Success
Not Achieved
n=41
Acute Procedural SuccessAchievedn=137
n=3781% Follow-up96% MR ≤2+ at 12 months
16Investigational Device only in the US; Not available for sale in the US
16
Patients randomized but not treated are included in ITT analysis
EVEREST II RCT: Patient FlowIntention to Treat Cohort: Analysis of Treatment
Strategy
Randomized Cohort n=279
Device Groupn=184
Control Groupn=95
12 monthsn=175
92% Follow-up
30 daysn=180
95% Follow-up
30 daysn=94
84% Follow-up
12 monthsn=89
78% Follow-up
17Investigational Device only in the US; Not available for sale in the US
0 20 40 60 80 100
EVEREST II RCT: Primary EndpointsPer Protocol Cohort