1 EVEREST II REALISM - A Continued Access Study To Evaluate The Safety And Effectiveness Of The MitraClip® Device: Demographics And Procedural Outcomes.

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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

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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

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Transcatheter Mitral Valve RepairMitraClip® System

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

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MitraClip TherapyWorldwide 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

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EVEREST II REALISMStudy Organization

A Continued Access Registry of the Evalve® MitraClip® System: EVEREST II Real World ExpAnded MuLtIcenter Study of the MitraClip System (REALISM)REALISM Trial

NAMSA (formerly Alquest, Inc.)Data Coordinating Center

John Giacomini MD, Jason Lee MD and Neil Schwartz MDStanford Hospital and Clinics

Clinical Events Committee

38 North American EVEREST II sitesEnrollment from 2009 to 2013

Enrolling Sites

Abbott VascularSponsor

Echocardiography Core Lab

Elyse Foster, MDUniversity of California, San Francisco

Neil J. Weissman, MDMedStar Health Research Institute

Principal Investigators

Ted Feldman, MDEvanston Northshore University HealthSystem

Donald Glower, MDDuke University Medical Center

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EVEREST II REALISM EnrollmentSite Principal Investigator High Risk Arm

(N=628)Non-High Risk Arm

(N=271)Total

(N=899)Evanston Hospital, IL Ted Feldman, MD 16 9 25Cedars-Sinai Medical Center, CA Saibal Kar, MD 77 50 127University of Virginia, VA David Scott Lim, MD 70 26 96Terrebonne General Medical Center, LA Peter Fail, MD 22 14 36Baptist Hospital of Miami, FL Ramon Quesada, MD 32 3 35Intermountain Medical Center, UT Brian Whisenant, MD 19 15 34St. Luke's Medical Center, WI Tanvir Bajwa, MD 26 6 32Carolina's Medical Center (Sanger Clinic), NC Michael Rinaldi, MD 18 11 29Baylor University Medical Center, TX Paul Grayburn, MD 24 5 29Memorial Hermann Hospital, TX Richard Smalling, MD 13 15 28Piedmont Hospital, GA Vivek Rajagopal, MD 21 6 27El Camino Hospital, CA Chad Rammohan, MD 12 15 27The Care Group Medical Center (St. Vincent Hospital), IN James Hermiller, MD 17 9 26Cleveland Clinic Foundation, OH Patrick Whitlow, MD 23 0 23Maine Medical Center, ME Mirle Kellett, Jr., MD 16 5 21Columbia University Medical Center, NY William Gray, MD 13 7 20Oklahoma Heart Hospital, OK Robert Kipperman, MD / John Williams, MD 12 8 20Morristown Memorial Hospital, NJ Robert Kipperman, MD 14 6 20Rush University Medical Center, IL Clifford Kavinsky, MD 16 4 20William Beaumont Hospital, MI George Hanzel, MD 17 2 19Duke University Medical Center, NC Andrew Wang, MD 14 3 17UC Davis Medical Center, CA Reginald Low, MD 13 4 17University of Colorado Health Sciences Center, CO John Carroll, MD 10 6 16Lenox Hill Hospital, NY Carlos E. Ruiz, MD, PhD 8 8 16Hospital of the University of Pennsylvania, PA Howard Herrmann, MD 7 8 15NYU Medical Center, NY James Slater, MD 8 7 15East Carolina Heart Institute Ramesh Dagubatti, MD / Curtis Anderson, MD 15 0 15Minneapolis Heart Institute, MN Wesley Pedersen, MD 10 4 14St. Patrick's Hospital & Health Science Center, MT Mark Sanz, MD / J. Tod Maddux, MD 12 1 13St Joseph’s Hospital, Atlanta Louis I. Heller, MD 11 1 12Washington Hospital Center, Washington DC Lowell Satler, MD 11 0 11St. Francis Hospital, NY Andrew Berke, MD 7 3 10Washington University School of Medicine, MO John Lasala, MD 5 3 8New York Presbyterian Hospital, NY S. Chiu Wong, MD 5 3 8Medical University of South Carolina Daniel H. Steinberg, MD 4 2 6Swedish Medical Center, WA Paul Huang, MD 5 0 5University of Texas Health Science Center, TX Steven R. Bailey, MD 2 2 4Shawnee Mission Medical Center, KS Paul Kramer, MD 3 0 3Total 628 271 899

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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

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.

High Risk Arm

The Non-High Risk (NHR) arm enrolled standard-risk patients. Non-High Risk Arm

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Purpose and Methods

• To present baseline demographics, clinical and acute procedural data results of the High Risk and Non-High Risk arms of EVEREST II REALISM

1 Zoghbi et al. J Am Soc Echocardiogr 2003;16:777-802

• 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

Purpose

Methods

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Key Inclusion/Exclusion CriteriaREALISM High Risk

• 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

• 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

Inclusion Exclusion

Bonow et al. 2008 Focused Update Incorporated Into ACC/AHA 2006 Guidelines (Writing Committee to Revise 1998 Guidelines). JACC 2008;52:e1-e142

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Key Inclusion/Exclusion CriteriaREALISM Non-High Risk

• 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

• 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

Inclusion Exclusion

Bonow et al. 2008 Focused Update Incorporated Into ACC/AHA 2006 Guidelines (Writing Committee to Revise 1998 Guidelines). JACC 2008;52:e1-e142

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Clinical Follow-UpEVEREST II REALISM

EVEREST II REALISMN=965

High Risk Arm N=628

Non-High Risk Arm N=271

Withdrew 5Missing 10

EnrolledJan 2009 - Dec 2013

EnrolledJan 2009 – Apr 2011

High Risk Arm30-Day Analysis

N=613(98% Clinical Follow-Up)

Withdrew 4Missing 5

Non-High Risk Arm30-Day Analysis

N=262(97% Clinical Follow-Up)

Compassionate and Emergency Use

N=66

Through data cut-off of February 7, 2015

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Baseline Demographics and Co-MorbiditiesEVEREST II REALISM

EVEREST II REALISM

Characteristics High-Risk Arm(N=628)

Non-High Risk Arm(N=271)

Age (mean ± SD) 77 ± 11 years 74 ± 11 yearsOver 75 years of age 63% 52%Male 60% 53%NYHA Functional Class III/IV 85% 54%Congestive Heart Failure 98% 82%Coronary Artery Disease 78% 49%Prior Myocardial Infarction 48% 19%Previous CABG 54% 17%Atrial Fibrillation 71% 56%Chronic Obstructive Pulmonary Disease 32% 22%Diabetes 36% 19%Moderate to Severe Renal Disease 30% 9%Cerebrovascular Disease 24% 13%STS Mortality Risk Score (mean ± SD) 11.1 ± 7.0% -

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Baseline Echocardiographic ParametersEVEREST II REALISM

EVEREST II REALISM

Characteristics High-Risk Arm(N=628)

Non-High Risk Arm(N=271)

Echo Core Lab Assessed MR ≥3+, (%) 81% 88%Functional MR Etiology 70% 32%Degenerative MR Etiology 30% 68%LV Ejection Fraction (mean ± SD) 47 ± 14% 56 ± 11%LV End Diastolic Volume (mean ± SD) 151 ± 55 ml 131 ± 43 mlLV End Systolic Volume (mean ± SD) 84 ± 45 ml 59 ± 30 mlLV End Diastolic Dimension (mean ± SD) 5.6 ±0.8 cm 5.3 ± 0.7 cmLV End Systolic Dimension (mean ± SD) 4.4 ± 1.1 cm 3.7 ± 0.9 cm

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MitraClip TherapyWorldwide Commercial Implant Experience

Data as of February 6, 2015. Source: Abbott Vascular

Etiology

Implant Rate: 96%

>20,000 Patients

FMR 65%DMR 22%

Mixed 13%

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Implant RateHigh Risk Arm

N=628Non-High Risk Arm

N=271

96.0% Implant Rate 95.2% Implant Rate

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Procedural and Post-Procedural Results

EVEREST II REALISM

Procedural and Post-Procedural Results High-Risk Arm(N=628)

Non-High Risk Arm(N=271)

Procedural (mean ± SD) Procedure time 139 ± 67 min 138 ± 68 minDevice time 107 ± 58 min 112 ± 64 minFluoroscopy duration 39 ± 24 min 35 ± 20 min

Post-Procedural (mean ± SD) ICU/CCU duration 1.5 ± 2.9 days 1.2 ± 2.9 daysLength of hospital stay 3.2 ± 4.6 days 2.8 ± 4.8 days

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Discharge Location

EVEREST II REALISM

Discharge Location High-Risk Arm(N=628)

Non-High Risk Arm(N=271)

Home 90.1% 96.3%Without home healthcare 83.3% 91.5%With home healthcare 6.8% 4.8%

Skilled Nursing Facility 5.4% 1.1%Nursing Home 2.4% 1.1%Long Term Acute Care 0.0% 0.4%Died Prior to Discharge 1.9% 0.7%

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Major Adverse Events at 30 DaysCEC Adjudicated

EVEREST II REALISM

Description of Event High-Risk Arm(N=628)

Non-High Risk Arm(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.

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Device Safety Results Through 30 Days

EVEREST II REALISM

Description of Event High-Risk Arm(N=628)

Non-High Risk Arm(N=271)

Single Leaflet Device Attachment (SLDA) 2.2% 3.5%

MV stenosis 0.8% 0.8%

Device Embolization 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%

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Mitral Regurgitation SeverityEcho Core Lab Assessed

High Risk Arm N=628

Non-High Risk Arm N=271

Paired Data (N=532) Paired Data (N=259)

p < 0.0001

90%

p < 0.0001

89%

N=survivors with paired data at 30 days or hospital discharge, whichever is longer post-procedure; p-values for descriptive purposes only

19% 12%

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NYHA Functional Class

High Risk Arm N=628

Non-High Risk Arm N=271

Paired Data (N=560) Paired Data (N=252)

p < 0.0001

82%

p < 0.0001

89%

15%

46%

N=survivors with paired data at 30 days; p-values for descriptive purposes only

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Change in LV Volumes and Dimensions From BaselineEcho Core Lab Assessed

LVESV (ml)

N=472; p<0.0001

N=227; p=0.9

LVIDs (cm)

N=255; p<0.0001

N=240; p=0.3

LVEDV (ml) LVIDd (cm)

N=227; p<0.0001

N=523; p<0.0001

N=500; p=0.0009N=471; p=0.2

N=survivors with paired data at 30 days or hospital discharge, whichever is longer post-procedure; p-values for descriptive purposes only

REALISM High Risk REALISM Non-High Risk

-9.2 [-11.6, -6.7]

-10.0 [-12.6, -7.3]

0.10 [-1.39, 1.59]

-1.5 [-3.5, 0.52]

-0.17 [-0.20, -0.13]

-0.18 [-0.22, -0.13]

-0.03 [-0.09, 0.03]

-0.07 [-0.11, -0.03]

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SF-36 Quality of LifeEVEREST II REALISM

N=survivors with paired data at 30 days; p-values for descriptive purposes onlyPCS = Physical Component Score; MCS = Mental Component Score

High Risk Arm N=628

Non-High Risk Arm N=271

Paired Data (N=499) Paired Data (N=93)

p < 0.0001 = 5.7 points

p < 0.0001 = 5.1 points

p < 0.0001 = 4.5 points

p < 0.0001 = 4.3 points

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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

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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

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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%).