Edwards Lifesciences Irvine, USA I Nyon, Switzerland I Tokyo, Japan I Singapore, Singapore I São Paulo, Brazil edwards.com

The Edwards SAPIEN transcatheter heart valve and delivery systems bearing the CE conformity marking comply with the requirements of the European Medical Device Directive 93/42/EEC. For professional use. See instructions for use for full prescribing information, including indications, contraindications, warnings, precautions, and adverse events.

Caution: not intended for uS distribution.

Edwards is a trademark of Edwards Lifesciences Corporation. Edwards Lifesciences, the stylized E logo, Edwards SAPIEN, and PARTNER are trademarks of Edwards Lifesciences Corporation and registered in the United States Patent and Trademark Office.

© 2010 Edwards Lifesciences Corporation. All rights reserved. E1679/11-10/THV

References

1. Data on file, Edwards Lifesciences LLC. 2. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363;1597-1607. 3. Spertus J, Peterson E, Conrad MW, et al. Monitoring clinical changes in patients with heart failure: a comparison of methods. Am Heart J. 2005;150:707-715. 4. National Institutes of Health. National Cancer Institute. Surveillance Epidemiology and End Results. Cancer Fact Sheets. http://seer.cancer.gov/statfacts/. Accessed November 16, 2010.

Establishing the New Standard of Care for Inoperable Aortic Stenosis

THE PARTNER TRIALCOHORT B RESULTS

E D W A R D S T R A N S C A T H E T E R H E A R T V A L V E P R O G R A M

• Superior survival

• Significantly improved cardiac function

• Dramatic reduction in symptoms

• Restored quality of life

A New Lifeline for Inoperable Aortic Stenosis Patients

T h e E d w a r d s S A P I E N T r a n s c a t h e t e r H e a r t V a l v e

T H E P A R T N E R T R I A L E S T A B L I S H I N G T H E N E w S T A N D A R D o f C A R E f o R I N o P E R A B L E A o R T I C S T E N o S I S

in all-cause mortality orhospitalization at 1 year(co-primary endpoint; P < .001)2

in cardiovascular mortalityat 1 year (P < .001)2

All

-Ca

use

Mo

rta

lity

, %

Months

100

80

60

40

20

00 6 12 18 24

P < .001∆ at 1 y = 20.0%NNT = 5.0 pts

Standard Therapy

Edwards THV

30.7%

50.7%

Co-PRImARy ENDPoINT: ALL-CAuSE moRTALITy1,2

absolute reduction29%

absolute reduction24%

Need to treat just 5 patients to save a life1

20%absolute reduction

in mortality 2

Despite expert care and frequent BAV (78.2%), standard therapy failed to alter the dismal

natural course of disease1

The Edwards SAPiEN THV Significantly improves Survival

NNT = 5

COHORT B POPULATiON PROfiLE1

Mean age 83 y

NYHA Class III-IV 93%

COPD, O2 dependent 23%

PVD 28%

Porcelain aorta 15%

Chest wall deformity 7%

CAD 71%

Frail 23%

Definitive Results Through Rigorous Design

The PARTNER (Placement of AoRtic TraNscathetER Valves) Trial represents a paradigm shift in clinical investigation and interpretability. As the world’s first prospective, randomized, and controlled trial for transcatheter heart valves, the PARTNER Trial sets new standards in site selection, case screening, study management, multidisciplinary teamwork, and patient follow-up.1

The PARTNER Trial consists of two individually powered patient cohorts.

• In Cohort A, the safety and effectiveness of the Edwards SAPIEN Transcatheter Heart Valve (THV) was compared to surgical aortic valve replacement (sAVR) in high-risk patients with severe aortic stenosis. The results of Cohort A are forthcoming.1

• In Cohort B, the safety and effectiveness of the Edwards SAPIEN THV was compared to best medical management (standard therapy) in inoperable patients with severe aortic stenosis. Patient selection required at least two cardiothoracic surgeons and an interventional cardiologist to agree that patients were not suitable candidates for surgery.1

CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; NYHA, New York Heart Association; PVD, peripheral vascular disease; BAV, balloon aortic valvotomy.

THE PARTNER TRIAL PRoToCoL1

No

Yes

Yes ASSESSMENTTransfemoral Access

Not in Study

TransfemoralStandardTherapyVS

Cohort Bn = 358

Cohort An = 700

ASSESSMENTOperability

No

1:1 Randomization

Symptomatic Severe Aortic Stenosis

T H E P A R T N E R T R I A L E S T A B L I S H I N G T H E N E w S T A N D A R D o f C A R E f o R I N o P E R A B L E A o R T I C S T E N o S I S

in all-cause mortality orhospitalization at 1 year(co-primary endpoint; P < .001)2

in cardiovascular mortalityat 1 year (P < .001)2

All

-Ca

use

Mo

rta

lity

, %

Months

100

80

60

40

20

00 6 12 18 24

P < .001∆ at 1 y = 20.0%NNT = 5.0 pts

Standard Therapy

Edwards THV

30.7%

50.7%

Co-PRImARy ENDPoINT: ALL-CAuSE moRTALITy1,2

absolute reduction29%

absolute reduction24%

Need to treat just 5 patients to save a life1

20%absolute reduction

in mortality 2

Despite expert care and frequent BAV (78.2%), standard therapy failed to alter the dismal

natural course of disease1

The Edwards SAPiEN THV Significantly improves Survival

NNT = 5

COHORT B POPULATiON PROfiLE1

Mean age 83 y

NYHA Class III-IV 93%

COPD, O2 dependent 23%

PVD 28%

Porcelain aorta 15%

Chest wall deformity 7%

CAD 71%

Frail 23%

Definitive Results Through Rigorous Design

The PARTNER (Placement of AoRtic TraNscathetER Valves) Trial represents a paradigm shift in clinical investigation and interpretability. As the world’s first prospective, randomized, and controlled trial for transcatheter heart valves, the PARTNER Trial sets new standards in site selection, case screening, study management, multidisciplinary teamwork, and patient follow-up.1

The PARTNER Trial consists of two individually powered patient cohorts.

• In Cohort A, the safety and effectiveness of the Edwards SAPIEN Transcatheter Heart Valve (THV) was compared to surgical aortic valve replacement (sAVR) in high-risk patients with severe aortic stenosis. The results of Cohort A are forthcoming.1

• In Cohort B, the safety and effectiveness of the Edwards SAPIEN THV was compared to best medical management (standard therapy) in inoperable patients with severe aortic stenosis. Patient selection required at least two cardiothoracic surgeons and an interventional cardiologist to agree that patients were not suitable candidates for surgery.1

CAD, coronary artery disease; COPD, chronic obstructive pulmonary disease; NYHA, New York Heart Association; PVD, peripheral vascular disease; BAV, balloon aortic valvotomy.

THE PARTNER TRIAL PRoToCoL1

No

Yes

Yes ASSESSMENTTransfemoral Access

Not in Study

TransfemoralStandardTherapyVS

Cohort Bn = 358

Cohort An = 700

ASSESSMENTOperability

No

1:1 Randomization

Symptomatic Severe Aortic Stenosis

T H E P A R T N E R T R I A L E S T A B L I S H I N G T H E N E w S T A N D A R D o f C A R E f o R I N o P E R A B L E A o R T I C S T E N o S I S

The Edwards SAPiEN THV Significantly improves Hemodynamics and Sustains Valve Performance

The Edwards SAPiEN THV Significantly improves Patient Symptoms and Quality of Life (QOL)

• Increase in ejection fraction at 1 year (P < .01)1

• Reduction in left ventricular mass index at 6 months and 1 year (P < .0001)1

• Reduction in mitral regurgitation at 1 year (P < .001)1

KCCQ, Kansas City Cardiomyopathy Questionnaire; MCID, minimum clinically important difference.

• 20-point improvement in KCCQ score represents change of large

clinical importance3

44.6

43.2

33.0

10.8

39.5

11.3

44.4

12.1

Me

an

Gra

die

nt,

mm

Hg 70

60

50

40

30

20

10

0 Baseline 30 Days 6 Months 1 Year N = 163 N = 143 N = 100 N = 89

P < .001Error bars = ± 1 SD

Standard TherapyEdwards THV

mEAN GRADIENTS oVER TImE1

KC

CQ

Sc

ore

70

60

50

40

30

20

10

0

∆ = 13.9P < .001

∆ = 20.7P < .001

∆ = 24.5P < .001

MCID = 5 ptsEdwards THV

Control

Months

0 2 4 6 8 10 12

KCCQ SCoRES oVER TImE1 AoRTIC VALVE AREAS (AVA) oVER TImE1

AV

A, c

m2

2.5

2.0

1.5

1.0

0.5

0

0.64

0.65

1.53

0.77

1.61

0.68

1.57

0.70

Baseline 30 Days 6 Months 1 Year N = 163 N = 143 N = 100 N = 89

P < .001Error bars = ± 1 SD

Standard TherapyEdwards THV

• Significant improvement observed as early

as 30 days (P < .001)2

I

II

III

IVPa

tie

nts

, %

100

80

60

40

20

0 Edwards Standard Edwards Standard THV Therapy THV Therapy Baseline 1 Year

P = .68 P < .001

NyHA CLASS oVER TImE2

Reduced mean gradient

(P < .001)2

Increased and sustained aortic

valve area (P < .001)2

25-point treament effect in KCCQ score

75% of the Edwards SAPiEN THV patients in

NYHA class i or ii at 1 year 2

T H E P A R T N E R T R I A L E S T A B L I S H I N G T H E N E w S T A N D A R D o f C A R E f o R I N o P E R A B L E A o R T I C S T E N o S I S

The Edwards SAPiEN THV Significantly improves Hemodynamics and Sustains Valve Performance

The Edwards SAPiEN THV Significantly improves Patient Symptoms and Quality of Life (QOL)

• Increase in ejection fraction at 1 year (P < .01)1

• Reduction in left ventricular mass index at 6 months and 1 year (P < .0001)1

• Reduction in mitral regurgitation at 1 year (P < .001)1

KCCQ, Kansas City Cardiomyopathy Questionnaire; MCID, minimum clinically important difference.

• 20-point improvement in KCCQ score represents change of large

clinical importance3

44.6

43.2

33.0

10.8

39.5

11.3

44.4

12.1

Me

an

Gra

die

nt,

mm

Hg 70

60

50

40

30

20

10

0 Baseline 30 Days 6 Months 1 Year N = 163 N = 143 N = 100 N = 89

P < .001Error bars = ± 1 SD

Standard TherapyEdwards THV

mEAN GRADIENTS oVER TImE1

KC

CQ

Sc

ore

70

60

50

40

30

20

10

0

∆ = 13.9P < .001

∆ = 20.7P < .001

∆ = 24.5P < .001

MCID = 5 ptsEdwards THV

Control

Months

0 2 4 6 8 10 12

KCCQ SCoRES oVER TImE1 AoRTIC VALVE AREAS (AVA) oVER TImE1

AV

A, c

m2

2.5

2.0

1.5

1.0

0.5

0

0.64

0.65

1.53

0.77

1.61

0.68

1.57

0.70

Baseline 30 Days 6 Months 1 Year N = 163 N = 143 N = 100 N = 89

P < .001Error bars = ± 1 SD

Standard TherapyEdwards THV

• Significant improvement observed as early

as 30 days (P < .001)2

I

II

III

IVPa

tie

nts

, %

100

80

60

40

20

0 Edwards Standard Edwards Standard THV Therapy THV Therapy Baseline 1 Year

P = .68 P < .001

NyHA CLASS oVER TImE2

Reduced mean gradient

(P < .001)2

Increased and sustained aortic

valve area (P < .001)2

25-point treament effect in KCCQ score

75% of the Edwards SAPiEN THV patients in

NYHA class i or ii at 1 year 2

T H E P A R T N E R T R I A L E S T A B L I S H I N G T H E N E w S T A N D A R D o f C A R E f o R I N o P E R A B L E A o R T I C S T E N o S I S

“ on the basis of a rate of death from any cause at 1 year that was 20 percentage points lower with TAVI than with standard therapy, balloon-expandable TAVi should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery.”

— The PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. Oct 2010 2

“ Rarely in medical research has so dramatic an improvement in survival been achieved in such a short time, with so few iterations.”

— Lars Svensson, MD, PhD, Cardiothoracic Surgeon, Cleveland Clinic, Cleveland, Ohio

“ The dramatic improvement in quality of life scores in the Edwards SAPIEN THV group is equivalent to a 10-year reduction in age.”

— David J. Cohen, MD, PhD, Cardiologist and Director of Cardiovascular Research, St Luke’s Mid America Heart and Vascular Institute, Kansas City, Missouri

with standard therapy, predicted survival of inoperable patients with aortic stenosis is lower than with certain metastatic cancers

Based on 1-year results of Cohort B patients treated with the Edwards SAPIEN THV:

Critical insights

to save a life1 5only need to treat

patientsout of

patients were asymptomatic or mildly

symptomatic2

3 4

Increased experience and next-generation technology may lower the incidence of acute major complications:

• Vascular complications (16.2%)2

• Bleeding episodes (16.8%)2

• Strokes (5.0%)2

*Using constant hazard ratio

23

Breast4 Lung4 Colorectal4 Prostate4 Ovarian4 Severe Inoperable AS*1

412

30

3

28

5-yEAR SuRVIVAL RATE, %

*Using constant hazard ratio.

T H E P A R T N E R T R I A L E S T A B L I S H I N G T H E N E w S T A N D A R D o f C A R E f o R I N o P E R A B L E A o R T I C S T E N o S I S

“ on the basis of a rate of death from any cause at 1 year that was 20 percentage points lower with TAVI than with standard therapy, balloon-expandable TAVi should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery.”

— The PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. Oct 2010 2

“ Rarely in medical research has so dramatic an improvement in survival been achieved in such a short time, with so few iterations.”

— Lars Svensson, MD, PhD, Cardiothoracic Surgeon, Cleveland Clinic, Cleveland, Ohio

“ The dramatic improvement in quality of life scores in the Edwards SAPIEN THV group is equivalent to a 10-year reduction in age.”

— David J. Cohen, MD, PhD, Cardiologist and Director of Cardiovascular Research, St Luke’s Mid America Heart and Vascular Institute, Kansas City, Missouri

with standard therapy, predicted survival of inoperable patients with aortic stenosis is lower than with certain metastatic cancers

Based on 1-year results of Cohort B patients treated with the Edwards SAPIEN THV:

Critical insights

to save a life1 5only need to treat

patientsout of

patients were asymptomatic or mildly

symptomatic2

3 4

Increased experience and next-generation technology may lower the incidence of acute major complications:

• Vascular complications (16.2%)2

• Bleeding episodes (16.8%)2

• Strokes (5.0%)2

*Using constant hazard ratio

23

Breast4 Lung4 Colorectal4 Prostate4 Ovarian4 Severe Inoperable AS*1

412

30

3

28

5-yEAR SuRVIVAL RATE, %

*Using constant hazard ratio.

Edwards Lifesciences Irvine, USA I Nyon, Switzerland I Tokyo, Japan I Singapore, Singapore I São Paulo, Brazil edwards.com

The Edwards SAPIEN transcatheter heart valve and delivery systems bearing the CE conformity marking comply with the requirements of the European Medical Device Directive 93/42/EEC. For professional use. See instructions for use for full prescribing information, including indications, contraindications, warnings, precautions, and adverse events.

Caution: not intended for uS distribution.

Edwards is a trademark of Edwards Lifesciences Corporation. Edwards Lifesciences, the stylized E logo, Edwards SAPIEN, and PARTNER are trademarks of Edwards Lifesciences Corporation and registered in the United States Patent and Trademark Office.

© 2010 Edwards Lifesciences Corporation. All rights reserved. E1679/11-10/THV

References

1. Data on file, Edwards Lifesciences LLC. 2. Leon MB, Smith CR, Mack M, et al. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med. 2010;363;1597-1607. 3. Spertus J, Peterson E, Conrad MW, et al. Monitoring clinical changes in patients with heart failure: a comparison of methods. Am Heart J. 2005;150:707-715. 4. National Institutes of Health. National Cancer Institute. Surveillance Epidemiology and End Results. Cancer Fact Sheets. http://seer.cancer.gov/statfacts/. Accessed November 16, 2010.

Establishing the New Standard of Care for Inoperable Aortic Stenosis

THE PARTNER TRIALCOHORT B RESULTS

E D W A R D S T R A N S C A T H E T E R H E A R T V A L V E P R O G R A M

• Superior survival

• Significantly improved cardiac function

• Dramatic reduction in symptoms

• Restored quality of life

A New Lifeline for Inoperable Aortic Stenosis Patients

T h e E d w a r d s S A P I E N T r a n s c a t h e t e r H e a r t V a l v e