ACORN CoreCap Trial Results: Implications for Cardiologists and Surgeons'

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ACORN CoreCap Trial ResultsImplications for
Cardiologists and Surgeons.

• Mariell Jessup MD
• Professor of Medicine
• University of Pennsylvania
• Philadelphia, Pennsylvania

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The Acorn Trial Clinical Evaluation of
the CorCapTM Cardiac Support Device in Patients
with Dilated Cardiomyopathy
Douglas L. Mann, M.D.
Michael Acker, M.D. Mariell Jessup,
M.D. Hani N. Sabbah, Ph.D Randall C.
Starling, M.D.
On behalf of the Acorn Trial Principal
Investigators and Study Coordinators
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The Unmet Need in Heart Failure

• Progressive LV dilation with a change in the
  shape of the heart from an ellipse to a more
  spherical shape are classic features of advancing
  heart failure
• LV remodeling predicts mortality in heart failure
  patients
• Despite optimal therapy heart failure remains a
  progressive disease that is accompanied by
  progressive LV remodeling
• No specific therapies for the treatment of
  progressive LV remodeling in patients with
  advancing heart failure

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CorCapTM Cardiac Support Device (CSD)

• Designed to reduce LV wall stress which is a
  primary determinant of LV remodeling
• Studied in 3 different animal models of heart
  failure1-4
• Human safety experience demonstrates structural
  clinical benefit out to 4 years 5

1JACC 2002392069 2 Circ Res 2003931095
3 Cardiovasc Res 199944549 4Circ 2002 106
(suppl I) I-207 5 JCTVS 2003126983
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The Acorn Trial
Hypothesis
Preventing LV remodeling with a cardiac support
device will favorably impact the untoward natural
history of heart failure.
Mann et al., J. Card Failure 2004 10 185-192
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Acorn Trial Clinical Centers and Core Labs
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Acorn Randomized Trial Design
300 Patients
Mitral Surgery Stratum 193 Patients
No Mitral Surgery Stratum 107 Patients
(Randomized)
(Randomized)
Control MVR Alone 102 Patients
Treatment MVR plus CSD 91 Patients
Control Med Rx Alone 50 Patients
Treatment Med Rx plus CSD 57 Patients
Common Closing Date July 4, 2004 with a Minimum
Follow-up of 1 year Intent-to-treat analysis
study powered for total of 300 patients Median
Follow-up of 23 Months (504 patient - years of
follow-up)
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Acorn Trial
Inclusion Criteria

• Men and women age 18-80 years of age
• NYHA class II IV HF of ischemic or non-ischemic
  etiology
• LVEF lt 35 and LVEDD gt 60 mm
• 6 minute walk test lt 450 meters
• Stable optimal medical therapy

Exclusion Criteria

• Planned cardiac surgical procedure other than MVR
• Patent CABG
• Planned LVAD implant or a transplant list

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Primary Endpoint Clinical Composite
Assessment of patient functional status after a
minimum of 12 months of follow-up
(1) Adjudicated Major Cardiac Procedures
indicative of HF Progression Transplant, LVAD,
CABG, BiV Pacing, and MV surgery (repeat)
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Baseline Characteristics
? Multiple etiologies possible
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Acorn Trial Baseline Medications
Minimum 3 month treatment
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Primary Endpoint Clinical Composite
Odds Ratio 1.73 (1.07-2.79) p 0.02
50
45
45
38
37
40
35
27
30
27
25
Percent of Patients
25
20
15
10
5
0
Improved
Unchanged
Worsened
As of common closing date July 4, 2004
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Freedom from Major Cardiac Procedures
CSD Treatment (n148)
100
90
80
Control (n152)
70
60
p 0.007
Free from Cardiac Procedures
50
Cardiac Procedure
Control
Treatment
40
Cardiac Transplant
n16
n7
30
LVAD
n8
n3
Bi-V Pacing
n14
n10
20
n3
MVR
n1
10
0
0
6
12
18
24
Months after Randomization
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Acorn Trial Survival
Control (n152)
100
90
80
CSD Treatment (n148)
70
60
50
p 0.90
Percent Survival
40
30
20
10
0
0
6
12
18
24
Months after Randomization
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Change in NYHA Classification
Odds Ratio 1.64 p 0.12
52
50
43
43
40
35
30
Percent of Patients
20
14
13
10
0
Improved
Unchanged
Worsened
(Censored for death and MCP)
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Reduction in LV End Diastolic Volume
3 Months 6 Months
12 Months n 217
n 200 n 185
0
-10
Change from Baseline in LVEDV (ml)
-20
-30
p 0.009
-40
Mean ? SEM
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Reduction in LV End Systolic Volume
3 Months 6 Months
12 Months n 217
n 200 n 185
15
10
5
0
-5
Change from Baseline in LVESV (ml)
-10
-15
-20
-25
p 0.017
-30
-35
Mean ? SEM
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Change in LV Ejection Fraction
6
p 0.45
4
Change from Baseline in EF (units)
2
0
-2
3 Months 6 Months
12 Months n 217
n 200 n 185
Mean ? SEM
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Change in LV Sphericity Index
0.14
p 0.026
0.12
0.1
0.08
Change from Baseline in Sphericity Index (units)
0.06
0.04
0.02
0
3 Months 6 Months
12 Months n 213 n
203 n 184
Mean ? SEM
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Change in Minnesota Living with Heart Failure
Questionnaire (MLHFQ)
3 Months 6 Months
12 Months n 260 n
250 n 244
0
-5
-10
Change from Baseline in MLHFQ (units)
-15
-20
p 0.05
-25
Mean ? SEM
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Change in SF 36 (Physical Function Domain)
25
p 0.015
20
15
Change from Baseline in SF 36 (units)
10
5
0
3 Months 6 Months
12 Months n 260 n
250 n 244
Mean ? SEM
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Acorn Trial Re-Hospitalizations
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Reportable Adverse Events (gt 5 Incidence)
No device related AEs No AEs related to Cardiac
Constriction
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No Mitral Surgery Stratum
Freedom from Major Cardiac Procedure
Primary Endpoint Clinical Composite
60
49
50
38
40
35
32
Percent of Patients
27
30
19
20
10
0
Improved
Same
Worsened
OR 2.56 (1.09- 6.05) p 0.03
p 0.03
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Summary of CSD Treatment Effects
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Comparative Changes in LV Size
Control
Treatment
25
10
-5
Change in LVEDV (ml)
-20
-35
Drugs
CRT
CSD
-50
1. Greenberg et al, Circ 1995 912573 2.
Doughty et al, JACC 1997 291060 3.
Medtronic SSE P010015 4. Young et al JAMA
20032892689
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Conclusions

• In patients with progressive HF on optimal
  medical therapy, treatment with the CSD favorably
  impacted the untoward natural history of HF, as
  indicated by
• Improved clinical composite score
• Fewer Major Cardiac Procedures
• Sustained improvement in LV size and shape
• Sustained improvement in Quality of Life
• Acceptable safety profile
• These results suggest that the CorCapTM CSD
  represents a novel and effective new therapy for
  patients with enlarged hearts