Aortic stenosisA brief summary of prevalence, guidelines,

new treatment options, and current data

20%BAlloon-exPAnDABle

trAnscAtheter Aortic VAlVe imPlAntAtion (tAVi)

ABSOLUTE REDUCTION IN ALL-CAUSE mORTALITy AT

ONE yEAR22

stAnDArD meDicAl therAPy*

2

A o r t i c VA lV e D i s e A s e i s c o m m o n i n e l D e r ly PAt i e n t s

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 5%.4 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.3

new options for Aortic Valve replacement Epidemiological studies have determined that more than one in eight people aged

75 and older have moderate or severe aortic stenosis (AS).1 Multiple surveys have

shown that many 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 under appreciated yet serious and growing public health problem that should be addressed.”

—V.T. Nkomo, Mayo Clinic, USA3

0

2%

4%

6%

8%

10%

12%

14%

45 45-54 55-64 65-74 >75

PR

EV

AL

EN

CE

OF

MO

DE

RA

TE

O

R S

EV

ER

E V

ALV

E D

ISE

AS

E

AGE (YEARS)

All valve diseaseMitral valve diseaseAortic valve disease

Prevalence of Valvu lar Heart Disease by Age3

3

A o r t i c s t e n o s i s i s l i f e - t h r e At e n i n g

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.7

“Unless investigation and surgery can be performed very quickly, death, whether sudden or not, is still unacceptably common in severe aortic stenosis.”

—J.B. Chambers & P. Das, Guy’s and St. Thomas’ Hospitals, London25

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

Progress ion of Aort ic Stenosis6

3

4

A o r t i c s t e n o s i s t r e At m e n t g u i D e l i n e s

According to the ESC Guidelines, severe AS is defined by these characteristics:

The 2012 ESC/EACTS guidelines for AS recommend valve replacement for Class Ipatients, i.e. those with severe AS and symptoms

8. 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 favoured by a “heart team” based on the individual risk profile.8

• Aortic valve area: < 1cm2 • Jet Velocity: > 4.0m/sec • Mean transvalvular pressure: > 40mmHg

“Surgical intervention should be performed promptly once even minor symptoms occur.”

—C.M. Otto, University of Washington School of Medicine, Seattle, Washington6

No Yes

No

No

No

Yes

Yes

Yes

Severe AS

Symptoms

LVEF < 50%

Symptoms or fall in bloodpressure below baseline

No Yes

Re-evaluate in 6 months

AVR

Physically active

Exercise test

Presence of risk factor and low/intermediateindividual surgical risk

Contraindicationfor AVR

No Yes

High risk for AVR Short life expectancy

No Yes No Yes

AVR or TAVI

TAVI Med Rx

ESC/EACTS AS Treatment Guidel ines8

4

5

t r e At m e n t i s u r g e n t A n D A o r t i c VA lV e r e P l A c e m e n t i s e f f e c t i V e

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.9 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.5

In recent decades, surgical AVR has consistently produced outstanding results in prolonging life and improving quality of life.8,11,12,13 Even among patients over the age of 80 years, functional outcomes have been excellent in patients after AVR.13 Survival is good, with 60% to 65% of patients who underwent AVR alive five years later,11,12 with improved quality of life.8 AVR takes patients out of full-time care or sedentary lifestyles, enabling a return to independence.

Pat ient Surv iva l 10

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

% S

urv

iva

l

YEARS

AVR, AsymptomaticAVR, SymptomaticNo AVR, AsymptomaticNo AVR, Symptomatic

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

% S

urv

iva

l

YEARS

AVR, AsymptomaticAVR, SymptomaticNo AVR, AsymptomaticNo AVR, Symptomatic

6

m A n y A o r t i c s t e n o s i s PAt i e n t s A r e n o t t r e At e D

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 30% 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

“Too many patients with severe symptomatic valve disease are denied surgery.” —B. Iung, Bichat Hospital, Paris2

0

20%

40%

60%

80%

100%

Bouma15 1999

Iung16

2005Pellikka17

2005Charlson18

2006Bach19

2007

No Surgery Surgery41 33 30 60 48

50 67 70 40 52

0

20%

40%

60%

80%

100%

Bouma15 1999

Iung16

2005Pellikka17

2005Charlson18

2006Bach19

2007

No Surgery Surgery41 33 30 60 48

50 67 70 40 52

Surgery vs No Surgery in AS Pat ients14

Reasons for AVR Non-Referra l 14

r e A s o n s m A n y A o r t i c s t e n o s i s PAt i e n t s D o n ’ t g e t n e e D e D t r e At m e n t

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.8

High Risk45%

Mild Symptoms25%

AS Not Severe

18%

Patient Preference

12%

7

t r A n s c At h e t e r t r e At m e n t o P t i o n A D D r e s s e s A n u n m e t n e e D

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. TAVI received the CE mark in 2007.

“Today, TAVI allows patients who are at very high surgical risk or with contraindications to surgical AVR to benefit from an effective treatment of AS.”

—D. Himbert, Bichat-Claude Bernard Hospital, Paris20

Transcatheter Aort ic ValveImplantat ion

7

Transfemoral Valve Implantation

Transapical Valve

Implantation

TransaorticValve

Implantation

8

t h e PA r t n e r t r i A l

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.22

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 2011.22

•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.22

cohort B PoPulAtion Profile

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%

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

No

Yes

YesASSESSMENT

Transfemoral Access

Not in Study

TransfemoralStandardTherapyVS

Cohort Bn = 358

Cohort An = 700

ASSESSMENTOperability

No

1:1 Randomization

Symptomatic Severe Aortic Stenosis

The PARTNER Tr ia l Protocol22

9

t h e e D w A r D s s A P i e n t h V s i g n i f i c A n t ly i m P r o V e s s u r V i VA l

Co-Pr imary Endpoint : A l l -Cause Morta l i ty22

“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 Investigators21

t h e e D w A r D s s A P i e n t h V s i g n i f i c A n t ly i m P r o V e s PAt i e n t s y m P t o m s A n D Q u A l i t y o f l i f e

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 Medical Therapy*

Edwards THV

30.7%

50.7%

KC

CQ

Sc

ore

70

60

50

40

30

20

10

0

∆ = 13.9P < .001

∆ = 20.7P < .001

∆ = 24.5P < .001

MCID = 5 pts

Edwards THV Control*

Months

0 2 4 6 8 10 12

KC

CQ

Sc

ore

70

60

50

40

30

20

10

0

∆ = 13.9P < .001

∆ = 20.7P < .001

∆ = 24.5P < .001

MCID = 5 pts

Edwards THV Control*

Months

0 2 4 6 8 10 12

Kansas Ci ty Cardiomyopathy Quest ionnai re (KCCQ) Scores Over T ime21

“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, St Luke’s Mid-America Heart and Vascular Institute, Kansas City, Missouri23

*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.

*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.

1 0

r e f e r s y m P t o m At i c A o r t i c s t e n o s i s PAt i e n t s t o A h e A r t t e A m

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.

TranscatheterValve Implantation

Balloon AorticValvuloplasty

Medical Management

Patient is referred to a heart team

Surgical AVR

High RiskLow Risk

Heart Team Evaluat ion

1 1

n e w t r e At m e n t o P t i o n s l e A D t o i n c r e A s e D r e f e r r A l , A w A r e n e s s , A n D P r o P e r t r e At m e n t

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.24

“A significant population of patients with AS are still treated medically.”

—S.C. Malaisrie, Bluhm Cardiovascular Institute, Northwestern University Memorial Hospital, Chicago, Illinois24

80%

70%

60%

50%

40%

30%

20%

10%

02006 (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)

Impact of TAVI on Referra ls24

want to Know more?You can access more information on both surgical AVR and TAVI on the

Edwards Lifesciences’ web site Edwards.com/eu. The site will also help you

to locate a heart center and to identify specialists near you who are trained

in the TAVI procedure.

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.

© 2012 Edwards Lifesciences Corporation. All rights reserved. E3154/08-12/THV

References

1. National Heart Lung and Blood Institute, U.S. National Institutes of Health. Heart Valve Disease. Accessed at www.nhlbi.nih.gov/health/dci/Diseases/hvd/hvd_whatis.html. November 12, 2010.

2. lung B, Baron G, Tornos P, et al. Valvular heart disease in the community: a European experience. Curr Probl Cardiol 2007; 32:609-61.

3. Nkomo VT, Gardin JM, Skelton TN et al. Burden of valvular heart diseases: a population-based study. Lancet 2006; 368:1005-11.

4. Lindroos M et al. Epidemiological studies estimate the prevalence of aortic stenosis at 5% in subjects over the age of 75 years. J Am Coll Cardiol 1993; 21:1220-5.

5. Chambers JB. Aortic stenosis. Eur J Echocardiography 2009; 10:111-19.

6. Otto M. Valve disease: timing of aortic valve surgery. Heart 200 Chart. In: Ross J Jr, Braunwald E. Aortic Stenosis. Circulation 1968; 38(suppl 1):61-7.

7. Lester SJ, Heilbron B, Gin K, et al. The natural history and rate of progression of aortic stenosis. Chest 1998; 113:1109-14.

8. Vahanian A, Alfieri O, Andreotti F, et al. Guidelines on the management of valvular heart disease. Eur Ht J 2012. Aug 24. Epub ahead of print.

9. Bonow RO, Carabello BA, Chatterjee K, et al. ACC/AHA 2006 Guidelines for the management of patients with valvular heart disease. Circulation 2006 Aug 1; 111(5):e84-231.

10. 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(2): 308-15.

11. Conti V, Lick SD. Cardiac surgery in the elderly: indications and management options to optimize outcomes. Clin Geriatr Med 2006; 22:559-74.

12. Chiappini B, Camurri N, Loforte A, et al. Outcome after aortic valve replacement in octogenarians. Ann Thorac Surg 2004; 78:85-9.

13. Sundt TM, Bailey MS, Moon MR, et al. Quality of life after aortic valve replacement at the age of >80 years. Circulation 2000; 102[suppl III]:III-70-111-74.

14. 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.

15. 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.

16. 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.

17. 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.

18. Charlson E, Legedza AT, Hamel MB. Decision-making and outcomes in severe symptomatic aortic stenosis. J Heart Valve Dis 2006; 15:312-21.

19. Bach DS, Cimino N, Deeb GM. Unoperated patients with severe aortic stenosis. J Am Coll Cardiol 2007; 50:2018-9.

20. 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.

21. Reynolds MR et al; PARTNER Trial Investigators. Health-related quality of life after transcatheter aortic valve replacement in inoperable patients with severe aortic stenosis. Circulation 2011; 124(18):1964-1972.

22. 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.

23. Cohen DJ. Health-related quality of life after transcatheter aortic valve implantation vs non-surgical therapy among inoperable patients with severe aortic stenosis. Results from the PARTNER trial. Presented at the American Heart Association’s Scientific Sessions, Chicago, IL, November 2010.

24. Malaisrie SC, Tuday E, Lapin B, et al. Transcather aortic valve implantation decreases the rate of unoperated aortic stenosis. Eur J Cardiotherac Surg; e-pub Jan 11, 2011.

25. Chambers JB, Das P. Treadmill exercise in apparently asymptomatic aortic stenosis. Heart 2001; 86:361-362.

*Patients in control arm received best medical management which frequently (78.2%) included balloon aortic valvuloplasty

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