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

Press Conference

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

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%

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

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

TAVI Standard Rx0

20

40

60

80

100

120

140

160

73

55

100

65

120

84

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