PML04248 Rev. A Effectiveness of Transcatheter Reduction of Significant Mitral Regurgitation in High Surgical Risk Patients with MitraClip ® : Final 5

PML04248 Rev. A

Effectiveness of Transcatheter Reduction of Significant Mitral

Regurgitation in High Surgical Risk Patients with MitraClip®:

Final 5 Year Results of The EVEREST II High Risk Registry

Saibal Kar, MD, FACCon behalf of the EVEREST II Investigators

ACC 2014Washington, DC

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Disclosure Statement of Financial Disclosure Statement of Financial InterestInterest

Saibal Kar, MD, FACC

• Grant/Research SupportGrant/Research Support

• Consulting Fees/HonorariaConsulting Fees/Honoraria

• Other Financial BenefitOther Financial Benefit

• Abbott Vascular, Atritech, Abbott Vascular, Atritech, AGA Medical , St Jude AGA Medical , St Jude Medical, Circulite, CoherexMedical, Circulite, Coherex

• Abbott Vascular, AGA Abbott Vascular, AGA Medical, Atritech, GoreMedical, Atritech, Gore

• CoherexCoherex

Within the past 12 months, I or my spouse/partner have had a financial Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below.interest/arrangement or affiliation with the organization(s) listed below.

Affiliation/Financial Relationship Company

Off-label use of products and investigational deviceswill be discussed in this presentation

The EVEREST II High Risk Registry was funded by Abbott Vascular

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MitraClip TherapyWorldwide Experience

• More than 13,000 patients have been treated with the MitraClip device worldwide Nearly 2,000 patients have been enrolled in prospective clinical trials worldwide

• A majority of patients are considered high risk for mitral valve (MV) surgery

• On October 24, 2013, FDA approved MitraClip for treating significant symptomatic DMR in patients who have been determined to be at prohibitive risk for MV surgery by a heart team

Data as of 3/14/2014. Source: Abbott Vascular

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BackgroundEVEREST II High Risk Registry

• The EVEREST II High Risk Registry was a prospective, multi-center single arm clinical study designed to assess the safety and effectiveness of the MitraClip device in patients with significant MR considered to be high risk for MV surgery

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BackgroundEVEREST II High Risk Registry

• One-year outcomes in the EVEREST II High Risk Registry have been reported*: Procedural safety demonstrated

Reduction of MR with the MitraClip device was associated with improved LV function, NYHA Class & Quality of Life, and a reduction in CHF hospitalizations

MV surgery was not required for any EVEREST II High Risk Registry patient through 1 year

• Five-year follow-up on all patients is complete and the EVEREST II High Risk Registry is closed

• Totality of DMR data in the EVEREST II High Risk Registry provided foundation for approved indication

*Whitlow et al. JACC 2012;59:130-9

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“Transcatheter MV repair may be considered for severely symptomatic patients (NYHA class III/IV) with chronic severe primary MR (stage D) who have a reasonable life expectancy but a prohibitive surgical risk because of severe comorbidities.”

Class IIb recommendationLevel of Evidence B

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Purpose

• To present final 5-year results from the EVEREST II High Risk Registry

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Study DesignEVEREST II High Risk Registry

• Symptomatic patients with significant MR (≥3+)

• Surgical risk based on a STS calculated risk score ≥12% or a surgeon estimated risk score ≥12% based on prespecified criteria

• Left ventricular function: EF>20%; LVESD<60mm

• Mitral valve anatomy suitable for the MitraClip Device

78 High Surgical Risk Patients Enrolled

Functional MRN=46 (59%)

Degenerative MRN=32 (41%)

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Study DesignPredicted Procedural Mortality Risk: STS-Calculated or Surgeon

Estimate• High Risk Eligibility = Risk Score ≥12% • STS calculated score or Surgeon estimate based on the

presence of at least one pre-specified co-morbidity1) Porcelain aorta or mobile ascending aortic atheroma2) Post-radiation mediastinum 3) Previous mediastinitis4) Functional MR with EF<405) Over 75 years old with EF<406) Re-operation with patent grafts7) Two or more prior chest surgeries8) Hepatic cirrhosis9) Three or more of the following:

a) Creatinine > 2.5 mg/dLb) Prior chest surgeryc) Age over 75d) EF<35

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Baseline Co-morbiditiesEVEREST II High Risk Registry

*Mirabel et al. European Heart Journal 2007;28:1358-65

Baseline Co-MorbiditiesEII - HRR

N=78

Euro Heart Survey*

Not Operated, N=193 Operated, N=203

Age (mean) 77 69 63

Gender, male (%) 63 47 53

NYHA Class III or IV (%) 90 70 65

History Coronary Artery disease (%) 85 60 38

Prior Cardiac Surgery (%) 59 7 3

Prior MI (%) 56 28 18

Hypertension (%) 90 53 47

Diabetes Mellitus (%) 41 21 10

COPD / Chronic Lung Disease (%) 35 21 11

Moderate to Severe Renal Failure (%) 23 n/a n/a

Atrial Fibrillation (%) 62 36 32

Ejection Fraction, % (mean) 54 48 56

LVIDs, cm (mean) 3.9 4.1 4.0

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Clinical Follow-UpEVEREST II High Risk Registry

Baseline: 78 Patients1st patient enrolled: February 14, 2007

Last patient enrolled:January 30, 2008

N = 8 Withdrawals

5-Years: 70 Patients90% Clinical Follow-Up

Median follow-up 3.05 years. 229 total patient-years of follow-up.

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Site-Reported Adverse Events Through 5 Years

EVEREST II High Risk Registry

IndexThrough30 Days

1 YearThrough2 Years

2 YearsThrough3 Years



Ad

vers

e E

ven

t Rat

es

(%)

Pe

r P

atie

nt-

Ye

ar

of F

ollo

w-u

p

30 DaysThrough1 Year

Cardiac

Vascular

Neurologic

Renal

AE Categories

Long-Term MitraClip Device SafetyEVEREST II High Risk Registry

Through 1 Year# (%) of patients

1 Year to 5 Years# (%) of patients

Single Leaflet Device Attachment (SLDA)

1 (1.3%) 0 (0.0%)

MV stenosis 0 (0.0%) 2 (2.7%)

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

Based on N=75 who were implanted with 1 or 2 MitraClip devices

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Kaplan-Meier Freedom From MortalityEVEREST II High Risk Registry

75.6%1 year

42.5%5 years

58.8%3 years

Baseline 6 Months 12 Months 2 Years 3 Years 4 Years 5 YearsMitraClip # At Risk 78 64 58 46 40 37 14

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Kaplan-Meier Freedom From MortalityEVEREST II High Risk Registry and Duke High Risk Cohort

EVEREST II High Risk Registry (N=78)

Duke High Risk Cohort (N=953)

Duke cohort data from Abbott Vascular Executive Summary. Presented March 20, 2013; Gaithersburg, MD. http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/CirculatorySystemDevicesPanel/UCM343684.pdf.

75.6%73.8%1 year

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Re-Interventions Through 5 YearsEVEREST II High Risk Registry

# (%) of patients

Time to Re-Intervention

Post-Index Procedure

Conversion to MV Surgery 2 (2.6%) 1.3 years3.2 years

Second Intervention to Place an Additional MitraClip

2 (2.6%) 45 days2.8 years

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Mitral Regurgitation GradeEVEREST II High Risk Registry

4+

3+

3+ 3+

2+2+

1+

1+

4+

3+

78% 82%

4+

2+

% MR ≤ 2+ at

1 and 5 Years

Baseline1 YearN=54

Baseline5 YearsN=24

p < 0.005p <

0.005p <

0.005p <

0.005

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

Reduction in LV Volumes at 1 and 5 Years


Mean +/-SD (ml)

N=54p<0.0001

N=54p<0.005

LVEDV (ml) at 1 Year

LVESV (ml) at 1 Year

-32.1

N=24p<0.0001

N=24p<0.05

LVEDV (ml) at 5 Years

Mean +/-SD (ml)

LVESV (ml) at 5 Years

-10.0

-38.2

-14.6

N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes onlyPML04248 Rev. A

Reduction in LV Dimensions at 1 and 5 Years


Mean +/-SD (cm)

LVIDs (cm) at 1 Year

LVIDd (cm) at 1 Year

Mean +/- SD (cm)

LVIDs (cm) at 5 Years

LVIDd (cm) at 5 Years

N=54p<0.0001

N=54p=ns

N=24p=ns

N=24p<0.05

-0.3

-0.1

-0.2

0.2

N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes onlyPML04248 Rev. A

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NYHA Functional ClassEVEREST II High Risk Registry

II

IV

III

III

II

II

II II

IV

III

74% 83%% NYHA I/II at 1 and 5 Years

III

p < 0.005p <

0.005p <

0.005p <

0.005

Baseline1 YearN=54

Baseline5 YearsN=24


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Septal Lateral Annular DimensionsEVEREST II High Risk Registry

Systolic SLAD Diastolic SLAD

p < 0.001p <

0.001 p = nsp = ns p < 0.001p <

0.001 p = nsp = ns

Baseline1 YearN=51

Baseline5 YearsN=21

Baseline1 YearN=51

Baseline5 YearsN=21


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EVEREST II High Risk Registry – 5 Year ResultsSummary• The EVEREST II High Risk Registry is the longest

prospective follow-up of a high surgical risk cohort treated for severe MR

• Clinical benefits provided by MitraClip are durable in high risk patients surviving through 5 years Reduction in MR Severity Improvement in LV Volumes and Dimensions Improvement in NYHA Functional Class

• No new or ongoing safety concerns through 5 years in this high risk population

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EVEREST II High Risk Registry – 5 Year ResultsConclusion

• The MitraClip procedure is a safe and durable therapeutic option for select patients with significant MR who are at high surgical risk

• Durability of outcomes demonstrated in this limited FMR population provides foundation for COAPT trial

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COAPT Trial

COAPT TRIAL OVERVIEW NPL 03976 Rev E CAUTION: Investigational device. Limited by Federal (U.S.) law to investigational use only.

Clinical Investigational Plan 11-512: Version 5.1, November 11, 2013. COAPT protocol approved by FDA July 27, 2012.

Objective

To evaluate the safety and effectiveness of the MitraClip System for treatment of functional mitral regurgitation (FMR ≥3+) in symptomatic heart failure subjects who are treated per standard of care and who have been determined by the site’s local heart team as not appropriate for mitral valve surgery

COAPT is an Abbott Vascular sponsored trial

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COAPT Trial



430 patients enrolled at up to 75 US sites

Randomize 1:1

Clinical and TTE follow-up: Baseline, Treatment, 1-week (phone), 1, 6, 12,

18, 24, 36, 48, 60 months

Control groupStandard of care

N=215

Symptomatic heart failure subjects who are treated per standard of care Determined by the site’s local heart team as not appropriate for mitral valve surgery

Specific valve anatomic criteria

MitraClipN=215

Significant FMR (≥3+ by core lab)

Trial design

2013 ACCF/AHA Guideline for the Management of Heart Failure: Circulation 2013; 128:e240-327


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COAPT Trial



Status as of March 18, 2014

Screened 318

Randomized 52

Roll-ins 25

Data on file at Abbott Vascular.


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COAPT Trial



For More Information

For more information, please contact:

[email protected]

http://www.COAPTtrial.com


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

EVEREST II and COAPT are Abbott Vascular Sponsored Clinical Trials.

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. PML04248 Rev. A

http://www.abbottvascular.com/ifu/

http://www.abbottvascular.com/

Documents

PML04248 Rev. A Effectiveness of Transcatheter Reduction of Significant Mitral Regurgitation in High Surgical Risk Patients with MitraClip ® : Final 5