Transcript at 1 Year - ClipTime

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, FACC
on behalf of the EVEREST II Investigators
ACC 2014
Washington, DC
PML04248 Rev. A
Disclosure Statement of Financial Interest
Saibal Kar, MD, FACC
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
Affiliation/Financial Relationship
• Grant/Research Support
• Consulting Fees/Honoraria
• Other Financial Benefit
Company
• Abbott Vascular, Atritech,
AGA Medical , St Jude
Medical, Circulite, Coherex
• Abbott Vascular, AGA
Medical, Atritech, Gore
• Coherex
Off-label use of products and investigational devices
will be discussed in this presentation
The EVEREST II High Risk Registry was funded by Abbott Vascular
PML04248 Rev. A
MitraClip Therapy
Worldwide 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
PML04248 Rev. A
Background
EVEREST 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
PML04248 Rev. A
Background
EVEREST 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
PML04248 Rev. A
Class IIb recommendation
Level of Evidence B
“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.”
PML04248 Rev. A
Purpose
• To present final 5-year results from the EVEREST II
High Risk Registry
PML04248 Rev. A
Study Design
EVEREST 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 MR
N=46
(59%)
Degenerative MR
N=32
(41%)
PML04248 Rev. A
Study Design
Predicted 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-morbidity
1)
2)
3)
4)
5)
6)
7)
8)
9)
Porcelain aorta or mobile ascending aortic atheroma
Post-radiation mediastinum
Previous mediastinitis
Functional MR with EF<40
Over 75 years old with EF<40
Re-operation with patent grafts
Two or more prior chest surgeries
Hepatic cirrhosis
Three or more of the following:
a)
b)
c)
d)
Creatinine > 2.5 mg/dL
Prior chest surgery
Age over 75
EF<35
PML04248 Rev. A
Baseline Co-morbidities
EVEREST II High Risk Registry
Baseline Co-Morbidities
EII - HRR
Euro Heart Survey*
N=78
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
*Mirabel et al. European Heart Journal 2007;28:1358-65
PML04248 Rev. A
Clinical Follow-Up
EVEREST II High Risk Registry
1st patient enrolled:
February 14, 2007
Baseline: 78 Patients
Last patient enrolled:
January 30, 2008
N = 8 Withdrawals
5-Years: 70 Patients
90% Clinical Follow-Up
Median follow-up 3.05 years. 229 total patient-years of follow-up.
PML04248 Rev. A
Site-Reported Adverse Events Through 5 Years
Adverse Event Rates (%)
Per Patient-Year of Follow-up
EVEREST II High Risk Registry
AE Categories
Cardiac
Vascular
Neurologic
Renal
Index
30 Days 1 Year
2 Years 3 Years 4 Years
Through Through Through Through Through Through
30 Days
1 Year 2 Years 3 Years 4 Years 5 Years
PML04248 Rev. A
Long-Term MitraClip Device Safety
EVEREST 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
PML04248 Rev. A
Kaplan-Meier Freedom From Mortality
EVEREST II High Risk Registry
75.6%
1 year
58.8%
3 years
Baseline 6 Months 12 Months 2 Years 3 Years 4 Years 5 Years
MitraClip # At Risk
78
64
58
46
40
37
14
42.5%
5 years
PML04248 Rev. A
Kaplan-Meier Freedom From Mortality
EVEREST II High Risk Registry and Duke High Risk Cohort
75.6%
73.8%
1 year
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.
PML04248 Rev. A
Re-Interventions Through 5 Years
EVEREST II High Risk Registry
# (%)
of patients
Time to Re-Intervention
Post-Index Procedure
Conversion to MV Surgery
2 (2.6%)
1.3 years
3.2 years
Second Intervention to Place
an Additional MitraClip
2 (2.6%)
45 days
2.8 years
PML04248 Rev. A
Mitral Regurgitation Grade
EVEREST II High Risk Registry
p < 0.005
p < 0.005
78%
82%
2+
1+
3+
1+
% MR ≤ 2+ at
1 and 5 Years
3+
2+
2+
4+
4+
3+
3+
4+
Baseline 1 Year
N=54
Baseline 5 Years
N=24
N = survivors with paired data; p-values for descriptive purposes only
PML04248 Rev. A
Reduction in LV Volumes at 1 and 5 Years
EVEREST II High Risk Registry
LVEDV (ml) at 1 Year
N=54
p<0.0001
-32.1
LVESV (ml) at 1 Year
N=54
p<0.005
LVEDV (ml) at 5 Years
N=24
p<0.0001
LVESV (ml) at 5 Years
N=24
p<0.05
-10.0
Mean +/-SD (ml)
-38.2
-14.6
Mean +/-SD (ml)
N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes only
PML04248 Rev. A
Reduction in LV Dimensions at 1 and 5 Years
EVEREST II High Risk Registry
LVIDd (cm) at 1 Year
N=54
p<0.0001
-0.3
LVIDs (cm) at 1 Year
N=54
p=ns
-0.1
Mean +/-SD (cm)
LVIDd (cm) at 5 Years
N=24
p=ns
-0.2
LVIDs (cm) at 5 Years
N=24
p<0.05
0.2
Mean +/- SD (cm)
N = survivors with paired data; p-values baseline vs 1 & 5 years, for descriptive purposes only
PML04248 Rev. A
NYHA Functional Class
EVEREST II High Risk Registry
p < 0.005
p < 0.005
74%
II
I
83%
II
III
III
I
% NYHA I/II at
1 and 5 Years
II
II
IV
III
Baseline 1 Year
N=54
IV
III
Baseline 5 Years
N=24
N = survivors with paired data; p-values for descriptive purposes only
PML04248 Rev. A
Septal Lateral Annular Dimensions
EVEREST II High Risk Registry
Systolic SLAD
p = ns
Baseline 1 Year
N=51
Baseline 5 Years
N=21
p < 0.001
p = ns
Baseline 1 Year
N=51
Baseline 5 Years
N=21
Mean SLADsyst (cm)
Mean SLADdiast (cm)
p < 0.001
Diastolic SLAD
N = survivors with paired data; p-values for descriptive purposes only
PML04248 Rev. A
EVEREST II High Risk Registry – 5 Year Results
Summary
• 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
PML04248 Rev. A
EVEREST II High Risk Registry – 5 Year Results
Conclusion
• 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
PML04248 Rev. A
COAPT Trial
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
Clinical Investigational Plan 11-512: Version 5.1, November 11, 2013. COAPT protocol approved by FDA July 27, 2012.
COAPT TRIAL OVERVIEW NPL 03976 Rev E
CAUTION: Investigational device. Limited by Federal (U.S.) law to investigational use only.
COAPT is an Abbott Vascular sponsored trial
PML04248 Rev. A
COAPT Trial
Trial design
430 patients enrolled at up to 75 US sites
Significant FMR (≥3+ by core lab)
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
Randomize 1:1
MitraClip
N=215
Control group
Standard of care
N=215
Clinical and TTE follow-up:
Baseline, Treatment, 1-week (phone), 1, 6, 12,
18, 24, 36, 48, 60 months
Clinical Investigational Plan 11-512: Version 5.1, November 11, 2013. COAPT protocol approved by FDA July 27, 2012.
COAPT TRIAL OVERVIEW NPL 03976 Rev E
CAUTION: Investigational device. Limited by Federal (U.S.) law to investigational use only.
2013 ACCF/AHA Guideline for the Management of Heart Failure: Circulation 2013; 128:e240-327
COAPT is an Abbott Vascular sponsored trial
PML04248 Rev. A
COAPT Trial
Status as of March 18, 2014
Screened
318
Randomized
52
Roll-ins
25
Data on file at Abbott Vascular.
Clinical Investigational Plan 11-512: Version 5.1, November 11, 2013. COAPT protocol approved by FDA July 27, 2012.
COAPT TRIAL OVERVIEW NPL 03976 Rev E
CAUTION: Investigational device. Limited by Federal (U.S.) law to investigational use only.
COAPT is an Abbott Vascular sponsored trial
PML04248 Rev. A
COAPT Trial
For More Information
For more information, please contact:
[email protected]
http://www.COAPTtrial.com
Clinical Investigational Plan 11-512: Version 5.1, November 11, 2013. COAPT protocol approved by FDA July 27, 2012.
COAPT TRIAL OVERVIEW NPL 03976 Rev E
CAUTION: Investigational device. Limited by Federal (U.S.) law to investigational use only.
COAPT is an Abbott Vascular sponsored trial
PML04248 Rev. A
Abbott Vascular
4045 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 or
photograph. MitraClip is a trademark of the Abbott Group of Companies. www.AbbottVascular.com
©2014 Abbott. All rights reserved. PML04248 Rev. A