Martin B. Leon, MD

on behalf of the

PARTNER Investigators

TCT 2010; Washington, DC; September 23, 2010

Transcatheter Aortic Valve Implantation in Inoperable Patients

with Severe Aortic Stenosis

Presenter Disclosure Information for PARTNER at TCT ; September 23, 2010

Martin B. Leon, M.D.Martin B. Leon, M.D.

Scientific Advisory Board Edwards Lifesciences, Medtronic, and Symetis

Equity Relationship Sadra

Scientific Advisory Board Edwards Lifesciences, Medtronic, and Symetis

Equity Relationship Sadra

Background

• There has been explosive growth in transcatheter aortic valve implantation (TAVI) since the first procedure in 2002.

• Although patient selection, operator skills, and technology have improved, all previous TAVI studies have been observational registries, without standardization of endpoint definitions.

• There is a paucity of evidence-based clinical data to substantiate incremental benefits of TAVI compared with current standard therapies.

Purpose

To assess the safety and effectiveness of TAVI compared with standard therapy, in patients with severe aortic stenosis and cardiac symptoms, who cannot undergo surgery (“inoperable”), using rigorous evidence-based clinical trial methodologies.

Symptomatic Severe Aortic StenosisSymptomatic Severe Aortic Stenosis

ASSESSMENT: High Risk AVR Candidate3105 Total Patients Screened

ASSESSMENT: High Risk AVR Candidate3105 Total Patients Screened

PARTNER Study Design

High Risk TAHigh Risk TA

ASSESSMENT: Transfemoral

Access

ASSESSMENT: Transfemoral

Access

TAVITrans

femoral

TAVITrans

femoral

Surgical AVR

Surgical AVR

High Risk TFHigh Risk TF

Primary Endpoint: All Cause Mortality (1 yr)(Non-inferiority)

Primary Endpoint: All Cause Mortality (1 yr)(Non-inferiority)

TAVITrans

femoral

TAVITrans

femoral

Surgical AVR

Surgical AVR

1:1 Randomization1:1 Randomization1:1 Randomization1:1 Randomization

VS

VS

Standard Therapy

(usually BAV)

Standard Therapy

(usually BAV)

ASSESSMENT: Transfemoral

Access

ASSESSMENT: Transfemoral

Access

Not In StudyNot In Study

TAVITrans

femoral

TAVITrans

femoral

Primary Endpoint: All Cause Mortality over length of trial (Superiority)

Primary Endpoint: All Cause Mortality over length of trial (Superiority)

1:1 Randomization1:1 Randomization

VS

Total = 1058 patientsTotal = 1058 patients

2 Parallel Trials: Individually Powered

2 Parallel Trials: Individually Powered

High Riskn= 700n= 700 Inoperable n=358n=358

Primary and Co-Primary Endpoints

• PRIMARY: All-cause mortality over the duration of the study

Superiority test (two-sided), 85% power to detect a difference, α = 0.05, sample size = 350 total patients

• CO-PRIMARY: Hierarchical composite of all-cause mortality and repeat hospitalization Non-parametric method described by Finkelstein and

Schoenfeld (multiple pair-wise comparisons) > 95% power to detect a difference, α = 0.05

• Positive study if both endpoints P < 0.05, or if either endpoint is < 0.025

Other Important Endpoints

• Cardiovascular mortality• Repeat hospitalization (after the index procedure)

Due to valve or procedure-related clinical deterioration Mortality and repeat hospitalization (KM analysis)

• Major strokes (modified Rankin Score ≥ 2 @ ≥ 30 days) Mortality and major strokes (KM analysis)

• Major vascular complications (VARC definition) • NYHA symptom classification• QOL and cost-effectiveness assessments• Six-minute walk tests• Echo assessments of valve function (core lab)

EOA, mean gradient, aortic regurgitation

Study Administration

• Co-Principle Investigators Martin B. Leon, Craig R. Smith

Columbia University Med Center

• Executive Committee Martin B. Leon, Michael Mack,

D. Craig Miller, Jeffrey W. Moses, Craig R. Smith, Lars G. Svensson, E. Murat Tuzcu, John G. Webb

• Data & Safety Monitoring Board Chairman: Joseph P. Carrozza

Tufts University School of Med

• Clinical Events Committee Chairman: John L. Petersen

Duke University Med Center

• Echo Core Laboratory Chairman: Pamela C. Douglas

Duke University Med Center

• Quality of Life and Cost Effectiveness Assessments

Chairman: David J. CohenMid-America Heart Inst, KC

• Independent Biostatistical Core Laboratory

Chairman: Stuart PocockLondon School of Hygiene &Tropical Medicine

William N. Anderson• Publications Committee

Co-Chairman: Jeffrey W. Moses, Lars G. Svensson

• Sponsor Edwards Lifesciences:

Jodi J. Akin

Executive Committee

Michael MackJohn Webb

Murat TuzcuCraig Miller

Marty LeonJeff Moses

Craig Smith

Lars Svensson

Total Enrollment

TF TA Total

High Risk SurgicalRoll-in 21 19 40

Randomized 493 207 700

Cont Access (non-rand)* 251 242 493

InoperableRoll-in 21 NA 21

Randomized 358 NA 358

Cont Access (rand) 91 NA 91

Cont Access (non-rand)* 132 NA 132

Overall 1,365 464 1,835

*as of September 1, 2010

Intermountain Medical CenterSalt Lake City

Emory University

Atlanta, GA

Univ. of MiamiMiami, FL

St. Luke’s Hospital Kansas City, MO

Barnes-Jewish HospitalSt. Louis, MO

Medical City DallasDallas, TX

St. Paul's HospitalVancouver, Canada

Univ of Washington Seattle, WA

Mayo ClinicRochester, MN

Stanford UniversityPalo Alto, CA

Hospital LavalQuebec City,

Canada

Ochsner FoundationNew Orleans, LA

Scripps ClinicLa Jolla, CA

Cedars-Sinai Medical CenterLos Angeles, CA

Cleveland ClinicCleveland, OH

Columbia University New York, NY

Washington Hosp. CenterWash., DC

Cornell UniversityUniv. Penn

Phila., PA

Mass GeneralBoston, MA Brigham & Women’s

Boston, MA

Northwestern Univ.Chicago, IL

Toronto Gen. HospitalCanada

Evanston Hospital

Leipzig Heart Center Leipzig, Germany

Total Enrollment

Univ. of Virginia Charlottesville, VA

n = 1058 patients26 Investigator Sites22 USA, 3 Canada, 1 Germany

Intermountain Medical CenterSalt Lake City

Emory University

Atlanta, GA

Univ. of MiamiMiami, FL

St. Luke’s Hospital Kansas City, MO

Barnes-Jewish HospitalSt. Louis, MO

Medical City DallasDallas, TX

St. Paul's HospitalVancouver, Canada

Univ of Washington Seattle, WA

Mayo ClinicRochester, MN

Stanford UniversityPalo Alto, CA

Hospital LavalQuebec City,

Canada

Ochsner FoundationNew Orleans, LA

Scripps ClinicLa Jolla, CA

Cedars-Sinai Medical CenterLos Angeles, CA

Cleveland ClinicCleveland, OH

Columbia University New York, NY

Washington Hosp. CenterWash., DC

Cornell UniversityUniv. Penn

Phila., PA

Mass GeneralBoston, MA Brigham & Women’s

Boston, MA

Northwestern Univ.Chicago, IL

Toronto Gen. HospitalCanada

Evanston Hospital

Leipzig Heart Center Leipzig, Germany

Enrollment - Inoperable

n = 358 patients21 Investigator Sites17 USA, 3 Canada, 1 Germany

Univ. of Virginia Charlottesville, VA

Cedars-Sinai Medical Ctr Los Angeles, CA G. Fontana, R. Makkar

169

Columbia University New York City, NY M. Leon, C. Smith

133

Medical City Dallas Dallas, TX D. Brown, M. Mack

120

Emory University Atlanta, GA P. Block, R. Guyton

118

Washington Hospital Ctr District of Columbia P. Corso, A. Pichard

99

Cleveland Clinic Found Cleveland, OH L. Svensson, M. Tuzcu

97

University of Pennsylvania Philadelphia, PA J. Bavaria, H. Herrmann

95

University of Miami Miami, FL W. O’Neill, D. Williams

44

Barnes-Jewish Hospital St. Louis, MO R. Damiano, J, Lasala

41

St. Paul's Hospital Vancouver, BC, Canada A. Cheung, J. Webb

41

Stanford University Palo Alto, CA C. Miller, A. Yeung

39

Northwestern University Chicago, IL C. Davidson, P. McCarthy

30

Overall Enrollment by Site

Overall Enrollment by Site St. Luke’s Hospital Kansas City, MO K. Allen, D. Cohen

24

Mass General Hospital Boston, MA I. Palacios, G. Vlahakis

24

Mayo Clinic Rochester, MN C. Rihal, T. Sundt

20

Scripps Clinic La Jolla, CA S. Brewster, P. Teirstein

20

Univ of Washington Seattle, WA M. Reisman, E. Verrier

19

Northshore Univ Health Sys Evanston, IL J. Alexander, T. Feldman

17

Universitaire de Quebec Laval, Quebec, CA D. Doyle, J. Rodes-Cabau

12

Herzzentrum Leipzig Leipzig, Germany F. Mohr, G. Schuler

11

University of Virginia Charlottesville, VA I. Kron, S. Lim

7

Brigham & Women’s Hosp Boston, MA M. Davidson, A. Eisenhauer

6

Cornell University New York City, NY K. Krieger, C. Wong

5

Ochsner Foundation New Orleans, LA E. Parrino, S. Ramee

5

Intermountain Med Center Salt Lake City, UT K. Jones, B. Whisenant

4

Toronto General Hospital Toronto, Ontario, CA C. Feindel, E. Horlick

2

Enrollment by Site - Inoperable

Cedars-Sinai Medical Ctr Los Angeles, CA G. Fontana, R. Makkar

36

Columbia University New York City, NY M. Leon, C. Smith

33

Medical City Dallas Dallas, TX D. Brown, M. Mack

21

Emory University Atlanta, GA P. Block, R. Guyton

43

Washington Hospital Ctr District of Columbia P. Corso, A. Pichard

50

Cleveland Clinic Found Cleveland, OH L. Svensson, M. Tuzcu

45

University of Pennsylvania Philadelphia, PA J. Bavaria, H. Herrmann

21

University of Miami Miami, FL W. O’Neill, D. Williams

15

Barnes-Jewish Hospital St. Louis, MO R. Damiano, J, Lasala

12

St. Paul's Hospital Vancouver, BC, Canada A. Cheung, J. Webb

22

Stanford University Palo Alto, CA C. Miller, A. Yeung

6

Northwestern University Chicago, IL C. Davidson, P. McCarthy

6

St. Luke’s Hospital Kansas City, MO K. Allen, D. Cohen

5

Mass General Hospital Boston, MA I. Palacios, G. Vlahakis

2

Mayo Clinic Rochester, MN C. Rihal, T. Sundt

7

Scripps Clinic La Jolla, CA S. Brewster, P. Teirstein

8

Univ of Washington Seattle, WA M. Reisman, E. Verrier

8

Northshore Univ Health Sys Evanston, IL J. Alexander, T. Feldman

10

Universitaire de Quebec Laval, Quebec, CA D. Doyle, J. Rodes-Cabau

4

Herzzentrum Leipzig Leipzig, Germany F. Mohr, G. Schuler

2

University of Virginia Charlottesville, VA I. Kron, S. Lim

0

Brigham & Women’s Hosp Boston, MA M. Davidson, A. Eisenhauer

0

Cornell University New York City, NY K. Krieger, C. Wong

0

Ochsner Foundation New Orleans, LA E. Parrino, S. Ramee

0

Intermountain Med Center Salt Lake City, UT K. Jones, B. Whisenant

0

Toronto General Hospital Toronto, Ontario, CA C. Feindel, E. Horlick

2

Enrollment by Site - Inoperable

Study Devices

Retroflex 1Edwards-SAPIEN THV

23mm and 26mmvalve sizes

22F and 24Fsheath sizes

Inclusion Criteria

• Severe calcific aortic stenosis defined as echo derived valve area of < 0.8 cm2 (EOA index <0.5cm2), and mean gradient > 40 mmHg or jet velocity > 4.0 m/s

• NYHA functional class II or greater• Risk of death or serious irreversible

morbidity as assessed by cardiologist and two surgeons must exceed 50%

Key Exclusion Criteria - 1

• Aortic valve is bicuspid or non-calcified• Aortic annulus diameter (echo measurement)

< 18 mm or > 25 mm• Aortic dissection or iliac-femoral dimensions or

disease which precludes safe sheath insertion• Severe LV dysfunction (LVEF < 20%)• Untreated CAD requiring revascularization• Severe AR or MR (> 3+) or prosthetic valve

(any location)

Key Exclusion Criteria - 2

• Serum Cr > 3.0 mg/dL or dialysis dependent• Acute MI within 1 month• Upper GI bleed within 3 months• CVA or TIA within 6 months• Any cardiac procedure, other than BAV, within 1

month or within 6 months for DES• Hemodynamic instability (e.g. requiring inotrope

support)• Life expectancy < 12 months (or little hope for

meaningful lifestyle recovery)

Patient Characteristics - 1

Characteristic TAVIn=179

Standard Rxn=179

P value

Age - yr 83.1 ± 8.6 83.2 ± 8.3 0.95

Male sex (%) 45.8 46.9 0.92

STS Score 11.2 ± 5.8 12.1 ± 6.1 0.14

Logistic EuroSCORE 26.4 ± 17.2 30.4 ± 19.1 0.04

NYHA I or II (%) III or IV (%)

7.892.2

6.193.9

0.680.68

CAD (%) 67.6 74.3 0.20

Prior MI (%) 18.6 26.4 0.10

Prior CABG (%) 37.4 45.6 0.17

Prior PCI (%) 30.5 24.8 0.31

Prior BAV (%) 16.2 24.4 0.09

CVD (%) 27.4 27.5 1.00

Patient Characteristics - 2

CharacteristicTAVI

n=179Standard Rx

n=179P value

PVD (%) 30.3 25.1 0.29

COPD Any (%) O2 dependent (%)

41.321.2

52.525.7

0.040.38

Creatinine >2mg/dL (%) 5.6 9.6 0.23

Atrial fibrillation (%) 32.9 48.8 0.04

Perm pacemaker (%) 22.9 19.5 0.49

Pulmonary HTN (%) 42.4 43.8 0.90

Frailty (%) 18.1 28.0 0.09

Porcelain aorta (%) 19.0 11.2 0.05

Chest wall radiation (%) 8.9 8.4 1.00

Chest wall deformity (%) 8.4 5.0 0.29

Liver disease (%) 3.4 3.4 1.00

Baseline Echocardiography(core lab)

Characteristic TAVIn=179

Standard Rxn=179

P value

Aortic valve area (cm2) 0.6 ± 0.2 0.6 ± 0.2 0.96

Mean AV gradient (mm Hg) 44.5 ± 15.7 43.0 ± 15.3 0.39

Mean LVEF (%) 53.9 ± 13.1 51.1 ± 14.3 0.06

Mod-Severe MR (%)(≥ 3+)

22.2 23.0 0.90

Procedural OutcomesTAVI (179 patients)

• 6 (3.4%) pts did not receive TAVI 2 died before scheduled implant 2 unsuccessful transfemoral access 2 intra-procedural annulus measurement too large and

procedure aborted

• After randomization, median time to TAVI was 6 days (inter-quartile range 3 - 11 days)

• During TAVI (first 24 hours) 2 (1.1%) deaths 3 (1.7%) major strokes 1 (0.6%) valve embolization 2 (1.1%) pts with multiple (≥ 2) valve implants

• In the first 30 days, 11 (6.4%) pts receiving TAVI died

Procedural OutcomesStandard Rx (179 patients)

• BAV performed in 114 (63.7%) pts ≤ 30 days and an additional 36 (20.1%) pts > 30 days after randomization (total BAV = 83.8% pts)

• Despite inoperable status: 12 (6.7%) pts received AVR 5 (2.8%) received LV - desc Ao conduit + AVR 4 (2.2%) received TAVI outside US

• 1-year mortality of pts receiving AVR, AVR-conduit, or TAVI (outside US): AVR - 33% AVR + conduit - 80% TAVI (outside US) - 0%

All Cause Mortality

Numbers at Risk

TAVI 179 138 122 67 26 Standard Rx 179 121 83 41 12

All

-cau

se m

ort

alit

y (%

)

Months

HR [95% CI] =0.54 [0.38, 0.78]

P (log rank) < 0.0001

Standard Rx

TAVI

All Cause Mortality

Numbers at Risk

TAVI 179 138 122 67 26 Standard Rx 179 121 83 41 12

Standard Rx

TAVI

All

-cau

se m

ort

alit

y (%

)

Months

∆ at 1 yr = 20.0%NNT = 5.0 pts

50.7%

30.7%

• Compare, at random, every TAVI patient with every Standard Rx patient; 179 x 179 (32,041) patient pairs, which did better?

• #1, compare “time to death” 72% chance that we know who died first If so, 63% chance that Standard Rx patient died first and

37% chance that TAVI patient died first

• #2, if necessary, compare “time to repeat hospitalization” 17% chance that we know who had repeat hosp first If so, 75% chance that Standard Rx patient had repeat

hosp first and 25% chance that TAVI patient had repeat hosp first

Finklestein & Schoenfeld Analysis(hierarchical multiple pair-wise comparison)

FS MethodProduces a

P-value< 0.0001

124/124 or 100% followedat 1 Yr

124/124 or 100% followedat 1 Yr

85/90 or 94.4% followedat 1 Yr

5 = Withdrawal = 0

89 = Death = 55

Study Flow - Inoperable

n=358Randomized Inoperable

n=358Randomized Inoperable

167/167 or 100% followedat 30 days

167/167 or 100% followedat 30 days

173/174 or 99.4% followedat 30 days

1 = Withdrawal = 0

5 = Death = 12

n=179TAVI

n=179TAVI

n=179Standard therapy

0 6 12 18 24

Cardiovascular Mortality

Numbers at Risk

TAVI 179 138 122 67 26 Standard Rx 179 121 83 41 12

Standard Rx

TAVI

Car

dio

vasc

ual

r m

ort

alit

y (%

)

Months

0

20

40

60

80

100

HR [95% CI] =0.39 [0.27, 0.56]

P (log rank) < 0.0001

0 6 12 18 24

Cardiovascular Mortality

Numbers at Risk

TAVI 179 138 122 67 26 Standard Rx 179 121 83 41 12

Standard Rx

TAVI

Car

dio

vasc

ual

r m

ort

alit

y (%

)

Months

0

20

40

60

80

100

∆ at 1 yr = 24.1%NNT = 4.1 pts

44.6%

20.5%

0 6 12 18 24

Mortality or Repeat Hosp

Standard Rx

TAVI

All

-cau

se m

ort

alit

y o

rR

epea

t H

osp

ital

izat

ion

(%

)

Months

0

20

40

60

80

100

Numbers at Risk

TAVI 179 117 102 56 22 Standard Rx 179 121 49 23 4

HR [95% CI] =0.46 [0.35, 0.59]

P (log rank) < 0.0001

0 6 12 18 24

Standard Rx

TAVI

All

-cau

se m

ort

alit

y o

rR

epea

t H

osp

ital

izat

ion

(%

)

Months

0

20

40

60

80

100

Numbers at Risk

TAVI 179 117 102 56 22 Standard Rx 179 121 49 23 4

∆ at 1 yr = 29.1%NNT = 3.4 pts

71.6%

42.5%

Mortality or Repeat Hosp

0 6 12 18 24

Mortality or Major Stroke

Standard Rx

TAVI

All

-cau

se m

ort

alit

y o

rM

ajo

r S

tro

ke (

%)

Months

0

20

40

60

80

100

Numbers at Risk

TAVI 179 132 118 56 25 Standard Rx 179 118 83 41 12

HR [95% CI] =0.58 [0.43, 0.78]

P (log rank) = 0.0003

0 6 12 18 24

Mortality or Major Stroke

Standard Rx

TAVI

All

-cau

se m

ort

alit

y o

rM

ajo

r S

tro

ke (

%)

Months

0

20

40

60

80

100

Numbers at Risk

TAVI 179 132 118 56 25 Standard Rx 179 118 83 41 12

∆ at 1 yr = 18.3%NNT = 5.5 pts

51.3%

33.0%

Outcome 30 Days n=179

TAVI Standard Rx P-value

 1 Year n=179

TAVI Standard Rx P-value

Clinical Outcomes at 30 Days & 1 Year

Myocardial infarction

All (%) 0 0 . 0.6 0.6 1.00 Peri-procedural (% 0 0 . 0 0 .

Stroke or TIA

All (%) 6.7 1.7 0.03 10.6 4.5 0.04 TIA (%) 0 0 . 0.6 0 1.00

Minor stroke (%) 1.7 0.6 0.62 2.2 0.6 0.37

Major stroke (%) 5.0 1.1 0.06 7.8 3.9 0.18

Death (all) or major stroke (%) 8.4 3.9 0.12 33.0 50.3 0.001

Repeat hospitalization (%) 5.6 10.1 0.17 22.3 44.1 <.0001

Death (all) or repeat hosp (%) 10.6 12.3 0.74 42.5 70.4 <.0001

Death

All (%) 5.0 2.8 0.41 30.7 49.7 0.0004

Cardiovascular (%) 4.5 1.7 0.22 19.6 41.9 <.0001

Outcome 30 Days n=179

TAVI Standard Rx P-value

 1 Year n=179

TAVI Standard Rx P-value

Clinical Outcomes at 30 Days & 1 Year

Acute kidney injury Creatinine >3 mg/dL (%) 0 1 1.00 1.1 2.8 0.45 RRT (%) 1.1 1.7 1.00 1.7 3.4 0.50

Cardiac re-intervention

BAV (%) 0.6 1.1 1.0 0.6 36.9 <.0001

Re-TAVI (%) 1.7 na 1.7 na

AVR (%) 0 1.7 0.25 1.1 9.5 <.0001

Endocarditis (%) 0 0 . 1.1 0.6 0.31

Vascular complications

All (%) 30.7 5.0 <.0001 32.4 7.3 <.0001

Major (%) 16.2 1.1 <.0001 16.8 2.2 <.0001

Bleeding - major (%) 16.8 3.9 <.0001 22.3 11.2 0.007

Arrhythmias

New atrial fibrillation (%) 0.6 1.1 1.00 0.6 1.7 0.62

New pacemaker (%) 3.4 5.0 0.60 4.5 7.8 0.27

P (log rank) = 0.069

Major Vascular Complication (n=31)

No Major Vascular Complication (n=148)

Mo

rta

lity

(%)

Months

Mortality vs. Major Vasc Complics TAVI patients

27.7%

47.2%

P (log rank) = 0.0046Major Bleed (n=46)

No Major Bleed (n=133)

Mo

rta

lity

(%)

Months

Mortality vs. Major Bleeding TAVI patients

26.3%

43.5%

Major Stroke (n=15)

No Major Stroke (n=164)

Mo

rta

lity

(%)

Months

P (log rank) <0.0001

Mortality vs. Major Stroke TAVI patients

27.7%

66.7%

Subgroup Analyses of Primary Endpoint (All-Cause Mortality)

TAVI better Standard Rx better

Subgroup TAVI (%)n=179

Standard Rx (%)n=179 RR (95% CI) RR (95% CI) NNT P

interaction

Overall 30.7 49.7 0.62 (0.47, 0.81) 5  

Age<85>85

29.232.5

51.1 48.3

0.57 (0.39, 0.83) 0.67 (0.46, 0.98)

56 0.54

SexFemaleMale

30.930.5

48.4 51.2

0.64 (0.44, 0.92)0.60 (0.40, 0.88)

65 0.80

Body-mass Index<25>25

38.624.0

52.9 46.7

0.73 (0.52, 1.02) 0.51 (0.34, 0.78)

74 0.20

STS score<11>11

23.738.4

42.1 54.9

0.56 (0.36, 0.88) 0.70 (0.51, 0.96)

56 0.44

LV ejection fraction<55>55

36.626.4

61.1 36.4

0.60 (0.43, 0.83) 0.73 (0.46, 1.14)

410 0.50

Subgroup Analyses of Primary Endpoint (All-Cause Mortality)

TAVI better Standard Rx better

Subgroup TAVI (%)n=179

Standard Rx (%) n=179 RR (95% CI) RR (95% CI) NNT P

interaction

Pulmonary hypertension

NoYes

26.135.4

45.549.4

0.57 (0.36, 0.92) 0.72 (0.50, 1.03)

57 0.47

Mitral regurgitation ≥3+

NoYes

32.323.7

46.560.5

0.70 (0.51, 0.95) 0.39 (0.21, 0.73)

73 0.09

COPD (02 dependent)NoYes

29.136.8

48.154.3

0.60 (0.44, 0.83) 0.68 (0.41, 1.11)

56 0.70

Prior CABG or PCINoYes

27.827.4

47.154.3

0.59 (0.38, 0.93) 0.50 (0.34, 0.75)

54 0.60

Peripheral vascular disease

NoYes

28.237.0

52.242.2

0.54 (0.39, 0.75) 0.88 (0.54, 1.43)

419 0.10

Walking Distance

P = 0.002

Wal

king

dis

tanc

e (m

eter

s)

Baseline 30 Days

Six-Minute Walk Tests

P = 0.004

1 Year

P = 0.67

P = 0.55

NYHA Class Over TimeSurvivors

P = 0.68 P < 0.0001 P < 0.0001 P < 0.0001

I II III IV

TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx TAVI Standard Rx

Per

cen

t

TreatmentVisit

Baseline 30 Day 6 Month 1 Year

BaselineN=163

30 DayN=143

6 MonthsN=100

1 YearN=89

Mea

n G

rad

ien

t (m

m H

g)

50

40

30

20

60

70

10

0

Error bars = ± 1 Std Dev

Mean Gradients Over Time

P < 0.0001

33.0

39.5

44.4

43.2 12.111.310.8

44.6

Standard Rx

TAVI

Paravalvular Regurgitation: TAVI

No changes over time

None/Trace

Mild

Moderate

Severe

30 Day 6 Month 1 Year

Conclusions - 1

In patients with severe AS and symptoms, who are not suitable candidates for surgery…

• Standard therapy (including BAV in 83.8% of pts) did not alter the dismal natural history of AS; all-cause and cardiovascular mortality at 1 year was 50.7% and 44.6% respectively

• Transfemoral balloon-expandable TAVI, despite limited operator experience and an early version of the system, was associated with acceptable 30-day survival (5% after randomization in the intention-to-treat population)

Conclusions - 2

• TAVI was superior to standard therapy, markedly reducing the rate of… all-cause mortality by 46%, P < 0.0001,

NNT = 5.0 pts cardiovascular mortality by 61%, P < 0.0001,

NNT = 4.1 pts all-cause mortality and repeat hospitalization

hierarchical (FS method), P < 0.0001 non-hierarchical (KM analysis) by 54%,

P < 0.0001, NNT = 3.4 pts

Conclusions - 3

• TAVI improved cardiac symptoms (NYHA class, P < 0.0001) and six minute walking distance (P = 0.002), after 1-year follow-up

• TAVI resulted in more frequent complications at 30 days, including… major vascular complications, 16.2% vs.

1.1%, P < 0.0001 major bleeding episodes, 16.8% vs. 3.9%,

P < 0.0001 major strokes, 5.0% vs. 1.1%, P = 0.06

Conclusions - 4

• Serial echocardiograms in TAVI patients indicated… reduced mean gradients (P < 0.0001) which

were unchanged during 1-year FU frequent paravalvular AR, which was usually

trace or mild (~90%), remained stable during 1-year FU, and rarely required further Rx.

Clinical Implications

• Balloon-expandable TAVI should be the new standard of care for patients with aortic stenosis who are not suitable candidates for surgery!

• Next generation devices (e.g. SAPIEN XT) may help to reduce the frequency of procedure-related complications in the future.

• The ultimate value of TAVI will depend on careful assessment of bioprosthetic valve durability, which will mandate obligatory long-term clinical and echocardiography FU of all TAVI patients.

September 22, 2010 on NEJM.org

Dedication

Thank you, to theoutstanding study sitesand to the courageous

patients who participated in the PARTNER Trial!