1 Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued...

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Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued Access High Surgical Risk – SCAI 2011

Comparison of EVEREST II High Surgical Risk and Continued Access High Surgical

Risk Patient Cohorts

1 Year Preliminary Results

Michael Rinaldi, Saibal Kar, Scott Lim, Ted Feldman, and the EVEREST II

InvestigatorsSCAI 2011

Baltimore, MD

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Disclosures

Consulting Fees/Honoraria• Abbott Vascular

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Percutaneous Mitral Valve Repair

MitraClip® System

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MitraClip TherapyWorldwide Clinical Experience

Over 3,000 patients have been treated with the MitraClip device worldwide:

• 75% are considered high risk* for mitral valve surgery

• 67% have functional mitral regurgitation (MR)

1,453 patients have been enrolled in prospective clinical trials worldwide:

• 50% are considered high risk* for mitral valve surgery

• 60% have functional MREstimates of worldwide clinical experience as of March 31, 2011

* Determination of high surgical risk based on: logistic EuroSCORE ≥ 20%, or STS calculated mortality ≥ 12%, or pre-specified high surgical risk comorbidities.

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High Surgical Risk Patients Treated with the

MitraClip Device in EVEREST II Trials

EVEREST High Surgical Risk Clinical Trials

EVEREST II – High Risk Trial 78

EVEREST II Continued Access – High Risk Trial

294

TOTAL High Surgical Risk Patients 372

As of April 12, 2011

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BackgroundEVEREST II Outcomes Through 2 Years

Randomized Controlled Trial (RCT) comparing percutaneous device and mitral valve surgery

• Percutaneous repair provides increased safety• Surgery provides more complete MR reduction• Both percutaneous and surgical treatment

reduced MR and demonstrated significant clinical benefits

High Risk study evaluating MitraClip device• Patients experienced reduced MR and significant

clinical benefits

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EVEREST II Continued Access 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, NCM Kellett, P Weldner, R Quinn Maine Medical Center, Portland, MER 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, TXV Rajagopal, J Kauten, W Mashman Piedmont Hospital, Atlanta, GAJ 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 Svenssen, E Roselli, L Rodriquez, W Stewart The Cleveland Clinic, Cleveland, OHW Gray, A Stewart, M Williams, M Argenziano, S Homma, R Pizzarello, L Gillam Columbia University, New York, NY; Danville, CTD Steinberg, F Crawford, J Ikonimidis, D Gregg, P Zwerner Medical University of South Carolina, Charleston, SCB 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, MNC Rammohan, C Vial, R Beygui, D Nair, A Prakash El Camino Hospital, Mountain View, CASC 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, NYC Ruiz, D Loulmet, V Subramanian, I Kronzon, N Marino Lenox Hill Hospital, New York, NYR Kipperman, S Lucas, RM Bodenhamer, J Randolph, J Williams Oklahoma Heart Hospital, Okalahoma City, OKZ Hijazi, R March, K Cao, J Soble Rush University Medical Center, Chicago, ILP 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, NYT Bajwa, D O’Hair, D Kress, K Sagar St. Luke’s Medical Center, Milwaukee, WIM Sanz, S Tahta, JM Maxwell, B Berry, J Knapp St. Patrick's Hospital & Health Science Ctr, Missoula,

MTM 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, LAR 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, VAR Kipperman, J Brown, D Cohen, H Hamrah Morristown Memorial Hospital, Morristown, NJK 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

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Purpose

To present initial safety and effectiveness data of MitraClip device in Continued Access “real world” high surgical risk patients • Enrollment is ongoing

To compare initial Continued Access high surgical risk study results to EVEREST II high surgical risk study results

To assess the impact of operator learning on outcomes of high surgical risk patients

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KEY INCLUSION CRITERIA• Predicted procedural mortality risk ≥ 12% (STS calculated or Surgeon estimated based on specific co-morbidities)• Symptomatic significant (3+ or 4+) MR• Etiology: Degenerative or Functional • Primary regurgitant jet originates from leaflet mal-coaptation at A2 / P2 region

KEY EXCLUSION CRITERIA• Evidence of an AMI in 2 weeks prior• EF ≤ 20% and/or LVESD > 60mm• Leaflet anatomy which may preclude MitraClip device implantation / proper positioning• Prior MV leaflet surgery• Echo evidence of intra-cardiac mass, thrombus, vegetation• Active endocarditis• Clip implant criteria

• Mitral valve area < 4 cm2

• Flail gap ≥ 10 mm, • Flail width ≥ 15 mm•Coaptation length < 2 mm

All high risk patients were enrolled using the same inclusion/exclusion criteria

Key Eligibility CriteriaEVEREST II and Continued Access High Surgical Risk

Patients

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High Surgical Risk Concurrent Control Group

Control group includes 36 patients screened for EVEREST II – High Surgical Risk• All patients met clinical eligibility criteria• All patients had significant MR (3+ to 4+) and

met high surgical risk criteria

Baseline co-morbidities well matched with EVEREST II High Surgical Risk Cohort

Management of MR through 1 year• 86% medical management • 14% mitral valve surgery

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Mitral Valve Anatomic CriteriaHigh Surgical Risk Concurrent Control

(N=36)

22%

20%

19%

11%

11%

8%

6%

3%

0% 10% 20% 30% 40%

Met all MitraClip anatomic criteria

No TEE performed

Leaflet calcification

MVA<4.0cm2

Jet origin other than A2-P2

Captation length >2mm

Flail width >15mm, or flail gap >10mm

Severely retracted posterior leaflet

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EVEREST II High Surgical Risk CohortEnrollment

* As of April 12, 2011, ^ Enrolled by February 28, 2010

1 YearN = 133

1 YearN = 78

REALISM High Surgical Risk Trial^

N = 294 Enrolled

EVEREST II High Surgical Risk CohortN = 372*

EVEREST II High Surgical Risk CohortWith 1 Year Follow-Up^

N = 211

EVEREST High Surgical Risk Trial^

N = 78 Enrolled

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Patient AccountabilityEVEREST II and Continued Access High Surgical Risk

Patients

EVEREST IIHigh Surgical Risk Patients

N = 78

211 EVEREST IIHigh Surgical Risk Patients

With 1 Year Follow-up

Enrolled by 28 Feb 2010

Continued Access High Surgical Risk Patients

N = 133

N = 1281 Year Analysis

N = 75 1 Year Analysis

N = 3 Withdrawals

N = 5 Withdrawals

96% of patient data available for analysis

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Baseline Demographics and Co-MorbiditiesEVEREST II and Continued Access High Surgical Risk

PatientsEVEREST II

High Surgical Risk Patients (N = 78)

Continued Access High Surgical Risk

Patients (N = 133)

p-value

Age, years, Mean ± SD 77 ± 10 76 ±11 0.43

Estimated Mortality Risk* (%) 18 ± 8 19 ± 8 0.73

Gender, male (%) 63 59 0.66

Coronary Artery Disease (%) 84 80 0.47

Atrial Fibrillation (%) 62 65 0.76

Moderate – Severe Renal Disease (%)

23 35 0.07

Prior CV Surgery (%) 59 58 0.89

Prior MI (%) 56 45 0.15

NYHA Class III/IV (%) 90 84 0.23

Functional MR (%) 59 78 0.008

LVEF, Mean ± SD (%) 54 ± 14 46 ± 13 < 0.001

LVID-s, Mean (cm) 3.9 ±1.1 4.5 ± 1.0 < 0.001*STS risk calculated or surgeon estimate based on prespecified co-morbidities

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Implant Rate and Procedural ResultsEVEREST II and Continued Access High Surgical Risk

PatientsEVEREST II



Patients (N = 133)

p-value

MitraClip Implant Rate (%) 96 95 0.80

0 MitraClips 4 5 n/a

1 MitraClip 59 62 n/a

2 MitraClips 37 33 n/a

MR ≤ 2+ at discharge, all patients (%) 72 88 0.009

MR ≤ 2+ at discharge for patients with MR ≥ 3+ at baseline (%)

71 81 0.20

Procedural Results (min)

Mean Procedure Time 190 153 < 0.001

Mean Device Time 145 117 0.005

Mean Fluoroscopy Duration 53 39 < 0.001

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Implant Rate and Procedural ResultsEVEREST II and Continued Access High Surgical Risk

Patients

EVEREST II High Surgical Risk

Patients (N = 78)


Patients (N = 133)

p-value

Post-Procedural Results

ICU Duration (hours) 52 25 0.005

Hospital Stay (days) 3.9 2.5 0.05

Discharged To, (%)

0.26

Home 80 87

Home With Home Health Care 10 8

Nursing Facility 10 3

Died Prior to Discharge 4 2

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Predicted vs Observed 30 Day Mortality EVEREST II and Continued Access High Surgical Risk

Patients

0

2

4

6

8

10

12

14

16

18

20

EVEREST II HR Continued Access HR

% M

orta

lity

PredictedObserved

7.7%

18.2%

P = 0.006

3.8%

18.2%

P < 0.0001

P = 0.34

N = 78 N = 133

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30 Day MAEEVEREST II and Continued Access High Surgical Risk

PatientsEVEREST II


# (%) Patients


Patients (N = 133)

# (%) Patients

p-value

Death 6 (7.7%) 5 (3.8%) 0.34

Major Stroke 2 (2.6%) 4 (3.0%) > 0.99

Re-operation of Mitral-Valve 0 0 n/a

Urgent / Emergent CV Surgery 0 1 (0.8%) > 0.99

Myocardial Infarction 2 (2.6%) 1 (0.8%) 0.56

Renal Failure 3 (3.8%) 1 (0.8%) 0.14

Deep Wound Infection 0 0 n/a

Ventilation >48 hrs 2 (2.6%) 2 (1.5%) 0.63

New Onset Permanent Atrial Fib 0 0 n/a

Septicemia 0 1 (0.8%) > 0.99

GI Complication Requiring Surgery 1 (1.3%) 0 0.37

Transfusions ≥ 2 Units 14 (17.9%) 16 (12.0%) 0.31

Total 21 (26.9%) 22 (16.5%) 0.08

Total Excluding Transfusions 10 (12.8%) 10 (7.5%) 0.23

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Investigator MitraClip Procedure Experience

EVEREST II and Continued Access High Surgical Risk Patients

EVEREST II High Surgical Risk

Patients (N = 78)


Patients (N = 133)

p-value

Number of Operators 25 34

Operator Experience:

Rolling average number of cases performed

10 23 < 0.0001

Median (Inter-quartile range) 7 (5, 16) 17 (8, 27)

* Includes patients treated in all EVEREST studies

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Baseline Demographics and Co-Morbidities EVEREST II, Continued Access and Concurrent

ControlEVEREST II

High Risk Patients

(N = 78)

Continued Access High Risk Patients

(N = 133)

Concurrent Control(N = 36)

Age, years, Mean ± SD 77 ± 10 76 ±11 77 ± 13

Estimated Mortality Risk (%) 18 ± 8 19 ± 8 17 ± 7

Gender, male (%) 63 59 50

Coronary Artery Disease (%) 84 80 71

Atrial Fibrillation (%) 62 65 53

Moderate – Severe Renal Disease (%)

23 35 31

Prior CV Surgery (%) 59 58 53

Prior MI (%) 56 45 36

NYHA Class III/IV (%) 90 84 84

Functional MR (%) 59 78 64

LVEF, Mean ± SD (%) 54 ± 14 46 ± 13^ 55 ± 18

LVID-s, Mean (cm) 3.9 ±1.1 4.5 ±1.0^ 3.8 ±1.1^p<0.001, REALISM HR vs CC

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EVEREST II High Risk

Continued Access High Risk

Kaplan-Meier Freedom from Death At 1 Year EVEREST II, Continued Access and Concurrent

Control

Concurrent Control

75.6%

75.2%

55.6%

1yr6m0 Days 30 Days# At RiskEVEREST II High RiskREALISM High RiskConcurrent Control

133 126 115 5378 72 64 58

36 32 28 20

p = 0.048 vs CC

p = 0.008 vs CC

At 1 Year

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Kaplan-Meier Freedom from MV Surgery At 1 Year

EVEREST II and Continued Access High Surgical Risk Patients

1yr6m0 Days 30 Days# At RiskEVEREST II High RiskREALISM High Risk 133 126 115 53

78 72 64 58

EVEREST II High Risk

Continued Access High Risk

100%

96.8%

At 1 Year

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Core Lab MR Grade at 1 Year (matched)EVEREST II and Continued Access High Surgical Risk

Patients

78%

0

20

40

60

80

100

Baseline 1 Year

Perc

ent Pa

tient

s 3+

4+3+

4+

2+

1+

2+

p < 0.0001

0

20

40

60

80

100

Baseline 1 Year

3+

4+3+

4+

2+

1+

83%

2+

0+

p < 0.0001

EVEREST IIHigh Surgical Risk Patients

(n=54 matched cases)



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LV End Diastolic and Systolic Volumes EVEREST II and Continued Access High Surgical Risk

PatientsEVEREST IIHigh Surgical Risk Patients


Continued AccessHigh Surgical Risk Patients


0

40

80

120

160

200

LVEDV LVESV

Baseline 1 Year

0

40

80

120

160

200

LVEDV LVESV

Baseline 1 Year

158 143

89 80

p = 0.0003 p = 0.011

172 140

82 72

Vo

lum

e (

mL

)

p < 0.0001 p = 0.0012

Baseline 1 year Baseline 1 year Baseline 1 year Baseline 1 year

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NYHA Functional Class at 1 Year EVEREST II and Continued Access High Surgical Risk

PatientsEVEREST II

High Surgical Risk Patients(n=54 matched cases)



0

20

40

60

80

100

Baseline 1 Year

Perc

ent

Patien

ts

II

III

IV

II

III

IV

I

0

20

40

60

80

100

Baseline 1 Year

II

III

IV

II

III

I

P < 0.0001 P < 0.0001

I

IV

74%84%

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SF-36 Quality of Life Scores at 1 Year EVEREST II and Continued Access High Surgical Risk

PatientsBaseline 1 Year

Continued Access HRn=70 matched

EVEREST II HRn=47 matched

Physical Component

p < 0.05 p < 0.001

Mental Component

p < 0.0001p < 0.06

Baseline 1 year Baseline 1 year Baseline 1 year Baseline 1 year

Continued Access HRn=70 matched

EVEREST II HR n=47 matched

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Hospitalization for CHFEVEREST II and Continued Access High Surgical Risk

Patients

0.86

0.45

0

0.2

0.4

0.6

0.8

1p=0.0002

1 Year Prior to MitraClip 1 Year Post MitraClip

48% Reduction0.65

0.36

0

0.2

0.4

0.6

0.8

1

An

nu

al R

ate

of

CH

F R

eh

op

*

p=0.02

45% Reduction

*CHF hospitalizations per patient-year

EVEREST II High Surgical Risk Patients


1 Year PriorN=78

1 Year PostN=75

1 Year PriorN=133

1 Year PostN=128

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Summary

Results consistent with previously demonstrated data in high surgical risk patients• MitraClip procedure safe• MitraClip device provides significant MR reduction and clinical benefits

– LV function, NYHA Function Class and Quality of Life (SF-36)

Procedural safety improved with increased experience• Significantly decreased procedure time with comparable effectiveness• Significantly decreased post-procedure ICU time and hospital stay• Decreased 30-day mortality

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Conclusion

The MitraClip procedure provides significant clinical benefits in select patients with significant MR who are at high risk for surgical mortality.

1 Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued...

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Transcript of 1 Investigational Device only in the U.S. Not available for sale in the U.S.EVEREST II and Continued...