Aortic StenosisA brief summary of prevalence, guidelines,new treatment options, and current data

2

Aortic Valve Disease is Common in Elderly Patients

New Options forAortic Valve Replacement

Prevalence of Valvular Heart Disease by Age 1

Epidemiological studies have determined that more than one in eight people aged 75 and older have moderate or severe aortic stenosis (AS).1 A study observed that many symptomatic patients with severe AS are not referred to a heart team for valve replacement evaluation.2 Surgical aortic valve replacement (SAVR) is the gold standard for treatment of severe AS and transcatheter aortic valve implantation (TAVI) offers a new treatment option for patients considered high risk for surgery. Here is how you can help.

“Valvular heart diseases represent an underappreciated yet serious and growing public health problem that should be addressed.” –V.T. Nkomo, Mayo Clinic, Rochester, USA

1

As the chart illustrates, aortic valve disease is common and its prevalence increases with age. For people over the age of 75 years, the prevalence of aortic stenosis is 3%.

More than one in eight people over the age of 75 have moderate or severe valve disease.1 As the population ages, this condition becomes an important public health problem.1

PR

EV

AL

EN

CE

OF

MO

DE

RA

TE

OR

SE

VE

RE

V

ALV

E D

ISE

AS

E

AGE (YEARS)

0 <45 45-54 55-64 65-74 ≥75

All valve disease

Mitral valve disease

Aortic valve disease

2%

4%

6%

8%

10%

12%

14%

3

Progression of Aort ic Stenosis 4

0

20 %

40 %

60 %

80 %

100 %

40 80

Onset Severe Symptoms

SU

RV

IVA

L

AGE (YEARS)

Latent Period(Increasing Obstruction,Myocardial Overload)

ANGINA SYNCOPE FAILURE

AVERAGE SURVIVAL (YEARS)

0 2 4 6

60

Aortic Stenosis is Life-threatening

Valvular aortic stenosis is progressive and life-threatening. Once symptoms appear, untreated patients have a poor prognosis; they will experience worsening symptoms,

eventually leading to death. After the onset of symptoms, average survival is 50% at two years and 20% at five years.4

“Unless investigation and surgery can be performed very quickly, death, whether sudden or not, is still unacceptably common in severe aortic stenosis.” –J. Chambers & P. Das, Guy’s and St. Thomas’ Hospitals, London

3

Aortic Stenosis Treatment Guidelines

European Society of Cardio logy AS Treatment Guidel ines 6

“Surgical intervention should be performed promptly once even minor symptoms occur.” – C.M. Otto, University of Washington School of Medicine, Seattle, Washington 5

The 2012 ESC/EACTS guidelines for AS recommend replacement for Class I patients, i.e. those with severe AS and symptoms. TAVI is indicated in patients with severe symptomatic AS who are not suitable for AVR as assessed by a “heart team” and should be considered in high risk patients who may still be suitable for surgery, but in whom TAVI is favored by a “heart team” based on the individual risk profile.6 The 2008 ACC/AHA guidelines recommend that AVR should be performed in virtually all symptomatic patients with severe AS. Both guidelines stress that age is not a contraindication to surgery.6,7

According to the ESC/EACTS Guidelines, severe AS is defined by the following echocardio-graphic characteristics:

6

• Aortic valve area: < 1 cm2 • Velocity ratio: < 0.25• Indexed valve area < 0.6 cm2/m2 body surface area • Jet velocity: > 4.0 m/s• Mean transvalvular pressure: > 40 mmHg

4

Symptoms

No

No

No

No

No

No

No

Yes

Yes

Yes

Yes No Yes

Yes

Yes

Yes

LVEF < 50%

Physically Active

Exercise Test

High risk for AVR Short life expectancy

Symptoms or fall in bloodpressure below baseline

Contraindicationfor AVR

Presence of risk factor and lowor intermediate individual surgical risk

Severe AS

Re-evaluate in 6 months

AVR AVR or TAVI TAVI Med Rx

Treatment is Urgent andAortic Valve Replacement is Effective

Pat ient Surv iva l 8

AVR, Asymptomatic

AVR, SymptomaticNo AVR, AsymptomaticNo AVR, Symptomatic

% S

urv

iva

l

There are no medications to reverse or slow the progression of AS. AVR is the standard of care. Because of the risk of sudden death, AVR should be performed promptly after the onset of symptoms.7 Without timely aortic valve replacement, patients with severe AS and symptoms have high mortality: mortality is 3% to 4% soon after symptoms appear and 7% among patients on a waiting list for AVR. In contrast, mortality in a fit patient is 1% to 2%after AVR.9

In recent decades, surgical AVR has consistently produced outstanding results in prolonging life and improving quality of life.6,10,11 Even among patients over the age of 80 years, functional outcomes have been excellent in patients after AVR.11 Survival is good, with 60% to 65% of patients who underwent AVR alive five years later,10,12 with improved quality of life.6 AVR takes patients out of full-time care or sedentary lifestyles, enabling a return to independence.

5

100

90

80

70

60

50

40

30

20

10

0

0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15

YEARS

Many Aortic Stenosis Patients are not Treated

0

20%

40%

60%

80%

100%

Bouma13

1999Iung14

2005Pellikka15

2005Charlson16

2006Bach17

2007

41 33 43 60 48

59 67 57 40 52

No Surgery

Surgery

Surgery vs No Surgery in AS Patients

Reasons for AVR Non-Referra l 18

Reasons Many Aortic Stenosis Patientsdon’t get Needed Treatment

"Analysis of patients with severe valve diseases showed that symptomatic patientswere frequently denied surgery"—B. Iung, Bichat Hospital, Paris 2

Guidelines are not consistently followed. In actual practice, more than one third of patients eligible for AVR are not referred for evaluation. As the chart illustrates, five different surveys identified 33% to 60% of patients not referred for surgery. Additionally, the Euro Heart Survey of 5000 patients from 92 centers in 25 European countries determined that 32.3% of patients over the age of 75 were denied surgery.2

Treatment decisions for older patients with severe AS are challenging due to comorbidity; they have a higher operative risk and have reduced life expectancy. In addition, their risk is increased by comorbidities such as heart disease and other conditions that are often present in this age group.6

6

High Risk34%

Other/ Unclear

19%

MildSymptoms

19%

Stenosis non-severe

14%

PatientPreference

9%

Decision under consideration

5%

Transcatheter Treatment Option Addresses an Unmet Need

Transcatheter Aort ic Valve Implantat ion

“Today, TAVI allows patients who are at very high surgical risk or with contraindica-tions to surgical AVR to benefit from an effective treatment of AS.”—D. Himbert, Bichat Hospital, Paris

19

A new option for patients with severe AS considered to be high risk for surgical AVR is transcatheter aortic valve implantation, or TAVI. In this procedure, the valve is delivered via transfemoral, transapical or transaortic access without open-heart surgery. The Edwards SAPIEN valve received the CE mark in 2007.

7

Transfemoral Valve Implantation

Transapical Valve Implantation

TransaorticValve Implantation

Porcelain aorta 15%

CAD 71%

Frail 23%

The PARTNER Trial

COHORT B POPULATION PROFILE

Mean age 83 y

NYHA Class III-IV 93%

COPD, O2 dependent 23%

PVD 28%

No

Yes

YesASSESSMENT

Transfemoral Access

TransfemoralTAVI

StandardTherapyVS

Cohort Bn = 358

Cohort An = 694

ASSESSMENTOperability

No

1:1 Randomization

Symptomatic Severe Aortic Stenosis

The PARTNER Tr ia l Cohort B 20

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.20

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 were published in 2011.21

• 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.20

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

8

Not inStudy

KC

CQ

Sc

ore

70

60

50

40

30

20

10

0

∆ = 13.3P < .0001

∆ = 20.8P < .0001

∆ = 26.0P < .0001

Minimal clinically important difference = 5 points

Months0 2 4 6 8 10 12

The Edwards SAPIEN THVSignificantly Improves Survival

Co-Pr imary Endpoint : A l l -Cause Morta l i ty 20

The Edwards SAPIEN THV Significantly Improves Patient Symptoms & Quality of Life

Kansas City Cardiomyopathy Questionnaire Scores Over Time 22

*Pat ients in contro l arm received best medical management which f requent ly (78.2%) inc luded bal loon aort ic va lvu loplasty.

“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 20

The magnitude of improvement in quality of life scores with TAVI was roughly equivalent to a 10-year reduction in age.22

9

Edwards THV Control*

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%

Among inoperable patients with severe AS, TAVI conferred a 25-point improvement in the KCCQ quality of life score after one year.22

Refer Symptomatic Aortic StenosisPatients to a Heart Team

Heart Team Evaluat ion

An increasing number of heart centers offer all of the available AS solutions. Referral to such a center offers the most options for your patients. A multidisciplinary approach is necessary in order to direct each patient toward the best therapeutic option. The team will evaluate patients for surgical AVR, balloon valvuloplasty, TAVI, or medical management.

10

Patient is referred to a heart team

Low Risk

Surgical AVR

High Risk

TranscatheterValve Implantation

Balloon AorticValvuloplasty

Medical Management

Impact of TAVI on Referra ls23

New Treatment Options Lead to Increased Referral, Awareness, and Proper Treatment

A retrospective study determined that the introduction of TAVI was associated with an increase in aortic valve replacement referrals and a decrease in the rate of unoperated AS. This positive impact was due to increases in both TAVI and AVR volume. Increased volume was not associated with worse patient survival.23

“A significant population of patients with AS are still treated medically.” – SC Malaisrie, Bluhm Cardiovascular Institute, Northwestern University Memorial Hospital, Chicago, Illinois 23

11

80%

70%

60%

50%

40%

30%

20%

10%

0

2006 (N=179)

Pre-TAVI Post-TAVI

2007 (N=183) 2008 (N=214) 2009 (N=265)

YEAR

(A) Unoperated AS (Pre-TAVI vs. Post-TAVI, p=.002)

(B) Referral for Surgery (Pre-TAVI vs. Post-TAVI, p=.003)

For professional use. See instructions for use for full prescribing information, including indications, contraindications,

warnings, precautions and adverse events.

Edwards Lifesciences devices placed on the European market meeting the essential requirements referred to in Article 3 of the Medical Device Directive 93/42/ECC bear the CE marking of conformity.

Any quotes used in this material are taken from independent third-party publications and are not intended to imply that such third party reviewed

or endorsed any of the products of Edwards Lifesciences.

Edwards, Edwards Lifesciences, the stylized E logo, Edwards SAPIEN, PARTNER and SAPIEN are trademarks of Edwards Lifesciences Corporation.

© 2014 Edwards Lifesciences Corporation. All rights reserved. E4583/01-14/THV

References

1. Nkomo VT, Gardin JM, Skelton TN, et al. Burden of valvular heart diseases: a population-based study. Lancet 2006;368:1005-11. 2. Iung B, Baron G, Tornos P, et al. Valvular heart disease in the community: a European experience. Curr Probl Cardiol 2007;32:609-61. 3. Chambers J, Das P. Treadmill exercise in apparently asymptomatic aortic stenosis. Heart 2001;86:361-2. 4. Ross J Jr, Braunwald E. Aortic stenosis. Circulation 1968;38:61-7. 5. Otto CM. Timing of aortic valve surgery. Heart 2000;84:211-8. 6. Joint Task Force on the Management of Valvular Heart Disease of the European Society of Cardiology (ESC); European Association for Cardio-Thoracic Surgery (EACTS), Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease (version 2012). Eur Heart J 2012;33:2451-96. 7. Bonow RO, Carabello BA, Chatterjee K, et al.; 2006 Writing Committee Members; American College of Cardiology/American Heart Association Task Force. 2008 Focused update incorporated into the ACC/AHA 2006 guidelines for the management of patients with valvular heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease): endorsed by the Society of Cardiovascular Anesthesiologists, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2008;118:e523-661. 8. Brown ML, Pellikka PA, Schaff HV, et al. The benefits of early valve replacement in asymptomatic patients with severe aortic stenosis. J Thorac Cardiovasc Surg 2008;135:308-15. 9. Chambers JB. Aortic stenosis. Eur J Echocardiogr 2009;10:i11-9. 10. Conti V, Lick SD. Cardiac surgery in the elderly: indications and management options to optimize outcomes. Clin Geriatr Med 2006;22:559-74. 11. Sundt TM, Bailey MS, Moon MR, et al. Quality of life after aortic valve replacement at the age of >80 years. Circulation 2000;102:III70-4. 12. Chiappini B, Camurri N, Loforte A, et al. Outcome after aortic valve replacement in octogenarians. Ann Thorac Surg 2004;78:85-9. 13. Bouma BJ, van Den Brink RB, van Der Meulen JH, et al. To operate or not on elderly patients with aortic stenosis: the decision and its consequences. Heart 1999;82:143-8. 14. Iung B, Cachier A, Baron G, et al. Decision-making in elderly patients with severe aortic stenosis: why are so many denied surgery? Eur Heart J 2005;26:2714-20. 15. Pellikka PA, Sarano ME, Nishimura RA, et al. Outcome of 622 adults with asymptomatic, hemodynamically significant aortic stenosis during prolonged follow-up. Circulation 2005;111:3290-5. 16. Charlson E, Legedza AT, Hamel MB. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis 2006;15:312-21. 17. Bach DS, Cimino N, Deeb GM. Unoperated patients with severe aortic stenosis. J Am Coll Cardiol 2007;50:2018-9. 18. van Geldorp MW, van Gameren M, Kappetein AP, et al. Therapeutic decisions for patients with symptomatic severe aortic stenosis: room for improvement? Eur J Cardiothorac Surg 2009;35:953-7. 19. Himbert D, Descoutures F, Al-Attar N, et al. Results of transfemoral or transapical aortic valve implantation following a uniform assessment in high-risk patients with aortic stenosis. J Am Coll Cardiol 2009;54:303-11. 20. Leon MB, Smith CR, Mack M, et al; PARTNER Trial Investigators. Transcatheter aortic-valve implantation for aortic stenosis in patients who cannot undergo surgery. N Engl J Med 2010;363:1597-607. 21. Smith CR, Leon MB, Mack MJ, et al.; PARTNER Trial Investigators. Transcatheter versus surgical aortic-valve replacement in high-risk patients. N Engl J Med 2011;364:2187-98. 22. Reynolds MR, Magnuson EA, Lei Y, et al.; Placement of Aortic Transcatheter Valves (PARTNER) Investigators. Health-related quality of life after transcatheter aortic valve replacement in inoperable patients with severe aortic stenosis. Circulation 2011;124:1964-72. 23. Malaisrie SC, Tuday E, Lapin B, et al. Transcatheter aortic valve implantation decreases the rate of unoperated aortic stenosis. Eur J Cardiothorac Surg 2011;40:43-8.

Want to Know More?You can access more information on both surgical AVR and TAVI on the Edwards Lifesciences’ website Edwards.com/eu. The site will also help youto locate a heart center and to identify specialists near you who are trained inthe TAVI procedure.

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