Final Results of the EVEREST II Randomized Controlled Trial of Percutaneous and Surgical Reduction of Mitral Regurgitation Ted Feldman, MD, FACC, FESC,

Final Results of the EVEREST II Randomized Controlled Trial of Percutaneous and Surgical

Reduction of Mitral Regurgitation

Ted Feldman, MD, FACC, FESC, FSCAIon behalf of the EVEREST II Investigators

ACC 2014Washington, DC

PML04247 Rev. A

Ted Feldman MD, FACC, FESC, FSCAI

Disclosure Information

The following relationships exist:

Grant support: Abbott, BSC, Edwards, WL GoreConsultant: 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

PML04247 Rev. A

EVEREST II RCT 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, R Makkar, 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 Svensson, 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 Katz St. 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

Interventional Cardiologist, Cardiac Surgeon, Echocardiologist

PML04247 Rev. A

Transcatheter Mitral Valve RepairMitraClip® System

All drawings are artist's representations only and should not be considered as an engineering drawing or photograph.

PML04247 Rev. A

BackgroundEVEREST 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

PML04247 Rev. A

BackgroundEVEREST II RCT

1Feldman et al. NEJM 2011;364:1395-406

PML04247 Rev. A

PurposeEVEREST II RCT

To present the final 5-year results from the EVEREST II RCT

MethodsEVEREST 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;16:777-802 PML04247 Rev. A

Key Inclusion/Exclusion CriteriaEVEREST II RCT

Inclusion• Candidate for MV Surgery• Moderate to severe (3+)

or severe (4+) MR– Symptomatic

o >25% EF & LVESD ≤55mm

– Asymptomatic with one or more of the following

o LVEF 25-60%o LVESD ≥40mmo Pulmonary hypertensiono 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

PML04247 Rev. A

Baseline CharacteristicsEVEREST II RCT

CharacteristicMitraClipN = 184

SurgeryN = 95

p-value

Age (mean), years 67 66 ns

Male 63% 66% ns

History of CHF 91% 78% 0.005

NYHA Functional Class III/IV 51% 47% ns

Functional MR Etiology 26% 27% ns

Coronary Artery Disease 47% 46% ns

Prior Myocardial Infarction 22% 21% ns

Previous Cardiovascular Surgery 22% 19% ns

Atrial Fibrillation 34% 39% ns

COPD (with or without home O2) 15% 15% ns

Moderate to Severe Renal Disease 3% 2% ns

Diabetes 8% 11% ns

LV Ejection Fraction (mean), % 60 61 ns

LV End Systolic Dimension (mean), cm 3.7 3.5 ns

PML04247 Rev. A

TreatedMitraClip Patients N=178

Aug 2005 - Nov 2008

Randomized Cohort N=279

TreatedSurgery Patients N=80

Clinical Follow-UpEVEREST II RCT

Untreatedn=6 MitraClip n=15 Surgery

81% Clinical Follow-Up

5-Year Analysis(N=145)

79% Clinical Follow-Up

5-Year Analysis(N=63)

WithdrawalsN=30 N=15N=3 N=2

N=258 Treated Patients

Missed Visits

Median follow-up 4.93 years. 1,007 total patient-years of follow-up.

PML04247 Rev. A

Site-Reported Adverse Events Through 5 Years

EVEREST II RCT

Cardiac

Vascular

Neurologic

Renal

AE Categories

IndexThrough30 Days

1 YearThrough2 Years

M

S

2 YearsThrough3 Years

M S

4 YearsThrough5 Years

3 YearsThrough4 Years

Ad

vers

e E

ven

t R

ate

s (%

)Per

Pati

en

t-Year

of

Follo

w-u

p

30 DaysThrough1 Year

M: MitraClipS: Surgery

M S M S M S M S

PML04247 Rev. A

Long-Term MitraClip Device SafetyEVEREST II RCT

Through 1 Year# (%) of patients

1 Year to 5 Years

# (%) of patients

Single Leaflet Device Attachment (SLDA)

10 (6.3%) 0 (0.0%)

MV stenosis 1 (0.6%) 0 (0.0%)

Device Embolization 0 (0.0%) 0 (0.0%)

Based on N=158 who were implanted with 1 or 2 MitraClip devices

PML04247 Rev. A

Kaplan-Meier Freedom From MortalityEVEREST II RCT

    Baseline 6 Months 12 Months 18 Months 2 Years 3 Years 4 Years 5 YearsMitraClip # At Risk 178 165 158 154 143 133 119 58Surgery # At Risk 80 76 70 70 65 57 52 24

93.7%92.3%1 year 81.2%

79.0%5 years

MitraClip (N=178)

Surgery (N=80)

PML04247 Rev. A

    Baseline 6 Months 12 Months 18 Months 2 Years 3 Years 4 Years 5 YearsMitraClip # At Risk 178 136 128 125 117 109 98 45Surgery # At Risk 80 75 69 68 63 54 49 21

78.9%97.4%1 year 74.3%

92.5%5 years

MitraClip (N=178)

Surgery (N=80)

Kaplan-Meier Freedom From MV Surgery in MitraClip Group or Re-operation in Surgery

Group

EVEREST II RCT

PML04247 Rev. A

6-Month Landmark Analysis

97.1%98.7%1 year 91.4%

93.7%5 years

Kaplan-Meier Freedom From MV Surgery in MitraClip Group or Re-operation in Surgery

Group

MitraClip

Surgery

EVEREST II RCT

PML04247 Rev. A

Mitral Regurgitation GradeEVEREST II RCT All Treated Patients (N=258)

MitraClip (N=178)MR ≤ 2+ at 1 and 5

Years

2+

4+

3+

2+

1+

2+

0+0+2+

4+

3+

Surgery (N=80)MR ≤ 2+ at 1 and 5

Years

2+

4+

3+

3+ 3+

2+

2+

1+1+

4+

3+

81% 82%

Baseline1 Year

0+

Baseline1 Year

99% 98%

1+

N=149Baseline5 Years

N=106

p < 0.005p <

0.005p <

0.005p <

0.005p <

0.005p <

0.005p <

0.005p <

0.005

N=66Baseline5 Years

N=41

N = survivors with paired data; p-values for descriptive purposes only PML04247 Rev. A

Reduction in LV Volumes at 1 and 5 Years

Mean ± SD (ml)

N=144p<0.0001

N=65p<0.0001

N=144p<0.0001

N=65p=0.05

LVEDV (ml) at 1 Year

LVESV (ml) at 1 Year

N=105p<0.0001

N=40p<0.0001

N=105p<0.01

N=40p<0.01

LVEDV (ml) at 5 Years

LVESV (ml) at 5 Years

Mean ± SD (ml)

SurgeryMitraClip

EII RCT

N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes onlyPML04247 Rev. A

Reduction in LV Dimensions at 1 and 5 Years

Mean ± SD (cm)

N=148p<0.0001

N=66p<0.0001

N=146p=ns

N=66p=ns

LVIDs (cm) at 1 Year

LVIDd (cm) at 1 Year

Mean ± SD (cm)

N=106p<0.0001

N=42p<0.0001

N=104p=ns

N=42p=ns

LVIDs (cm) at 5 Years

LVIDd (cm) at 5 Years

SurgeryMitraClip

EII RCT

N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes onlyPML04247 Rev. A

NYHA Functional ClassEVEREST II RCT All Treated Patients (N=258)

MitraClip (N=178)NYHA I/II at 1 and 5

Years

II

IV

III

III

IIII

I

I

II

IV

III

Surgery (N=80)NYHA I/II at 1 and 5

Years

II

IV

III

III

II

II

II

II

IV

III

98% 91% 88% 98%I I

I I

p < 0.005p <

0.005p <

0.005p <

0.005p <

0.005p <

0.005p <

0.005p <

0.005

Baseline1 YearN=151

Baseline5 YearsN=106

Baseline1 YearN=66

Baseline5 YearsN=42

N = survivors with paired data; p-values for descriptive purposes only PML04247 Rev. A

Septal Lateral Annular Dimensions EVEREST II RCT All Treated Patients - MitraClip Group

(N=178)MitraClip (N=178)

Systolic SLAD at 1 and 5 Years

N = survivors with paired data; p-values for descriptive purposes only

MitraClip (N=178)Diastolic SLAD at 1 and 5

Years

p = nsp = ns p = nsp = ns

Baseline1 YearN=124

Baseline5 YearsN=90

p < 0.05p < 0.05 p = nsp = ns

Baseline1 YearN=124

Baseline5 YearsN=90

PML04247 Rev. A

Long-Term Durability of Clinical Success

EVEREST II RCTClinical 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

5-Year Outcomes in Patients Who Were Alive and Free From

MR 3+/4+ and MV Surgery (or Re-Operation) at 1 Year

MR, NYHA and LV data are from survivors with paired data; freedom from events data are from Kaplan-Meier estimates

PML04247 Rev. A

EVEREST II RCT – 5 Year ResultsSummary

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

PML04247 Rev. A

EVEREST II RCT – 5 Year ResultsConclusions

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

PML04247 Rev. A

Abbott Vascular4045 Campbell Avenue, Menlo Park, CA 94025 USA, Tel: 1.650.833.1600

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 http://www.abbottvascular.com/ifu/ 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 orphotograph. MitraClip is a trademark of the Abbott Group of Companies. www.AbbottVascular.com

©2014 Abbott. All rights reserved. PML04247 Rev. A