two-year outcomes of transcatheter aortic valve...

TCT 2012 | Miami, FL | October 24, 2012

Three-Year Outcomes of Transcatheter Aortic Valve Replacement (TAVR) in “Inoperable” Patients With Severe Aortic Stenosis: The PARTNER Trial

Samir R. Kapadia, MD On behalf of The PARTNER Trial Investigators

Background (1)

• Transcatheter aortic valve replacement (TAVR) is

the recommended treatment for “inoperable”

patients with severe aortic stenosis (AS), based

upon 1-year results of The PARTNER Trial which

demonstrated reduced mortality and improved

quality of life.

• However, whether clinical benefit and valve

performance are sustained beyond two years

is unknown and longer term outcomes will

importantly alter clinical practice decisions.

Background (2)

Objectives

• To evaluate the clinical outcomes of TAVR

compared to standard therapy at 3 years in

“inoperable” aortic stenosis patients.

• To assess valve hemodynamics and durability

using echocardiography.

• To perform subgroup analyses to better define

the impact of co-morbidities on outcomes.

PARTNER Study Design

n = 358 Inoperable

Standard

Therapy

n = 179

ASSESSMENT:

Transfemoral

Access

TF TAVR

n = 179

Primary Endpoint: All-Cause Mortality

Over Length of Trial (Superiority)

1:1 Randomization

VS

Symptomatic Severe Aortic Stenosis

• Primary endpoint evaluated when all patients reached one year follow-up.

• After primary endpoint analysis reached, patients were allowed to cross-over to TAVR.

Inclusion Criteria

• Severe calcific aortic stenosis defined as echo

derived valve area of < 0.8 cm2 (EOA index

< 0.5 cm2/m2), and mean gradient > 40 mmHg

or jet velocity > 4.0 m/s.

• NYHA functional class ≥ II

• Inoperable defined as risk of death or serious

irreversible morbidity of AVR as assessed by

cardiologist and two surgeons exceeding 50%.

Key End-Points for 3 Year Analysis

• All cause mortality

• Cardiac mortality

• Rehospitalization

• Adverse outcomes including stroke, bleeding,

renal failure, and MI

• NYHA functional class

• Days alive and out of hospital

• Echo-derived valve areas, transvalvular gradients,

and paravalvular aortic regurgitation

• Mortality outcomes stratified by STS score

n = 358

Randomized Inoperable

n = 179

TAVR

n = 179

Standard Therapy

124/124 patients 100% followed at 1 Yr


101/102 patients* 99.0% followed at 2 Yr


Study Flow Inoperable Cohort

• *One TAVR patient was alive and censored prior to the window

• **Two TAVR patients were alive and censored prior to the window (including the one in the same status at 2 years); one TAVR patient withdrew between 2 and 3 years

• No patients were lost to follow-up

80/82 patients** 97.6% followed at 3 Yr


Cross over

11 pts

Cross over

9 pts

Statistical Method

• Primary analysis was by “intention-to-treat” (ITT).

• Clinical outcomes were analyzed by ITT with

censoring of Standard Rx cross-over patients.

• Additional analysis of death was performed by

following cross-over patients with their randomized

trial arms.

• Event rates are given as Kaplan-Meier estimates.

• Core lab echo results are presented from

the valve implant population (valve retained

in position).

Patient Characteristics (1)

Characteristic TAVR n = 179

Standard Rx n = 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

NYHA

I or II (%)

III or IV (%)

7.8

92.2

6.1

93.9

0.68

0.68

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

Note: Same as previously presented at TCT 2010 and published in the NEJM manuscript.

Patient Characteristics (2)


Standard Rx n = 179

p value

PVD (%) 30.3 25.1 0.29

COPD

Any (%)

O2 dependent (%)

41.3

21.2

52.5

25.7

0.04

0.38

Creatinine > 2 mg/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

Note: Same as previously presented at TCT 2010 and published in the NEJM manuscript.

Numbers at Risk

Standard Rx 179 121 85 62 46 27 17

TAVR 179 138 124 110 101 88 70

All Cause Mortality (ITT) Crossover Patients Censored at Crossover

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

30.7%

50.8%

43.0%

68.0%

54.1%

80.9%

All

Cause M

ort

alit

y (

%)

Months

HR [95% CI] = 0.53 [0.41, 0.68]

p (log rank) < 0.0001

20.1%

25.0%

26.8%

NNT = 5.0 pts

NNT = 4.0 pts

NNT = 3.7 pts

Standard Rx

TAVR

Cardiovascular Mortality (ITT) Crossover Patients Censored at Crossover

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

20.5%

44.6%

30.7%

62.4%

41.4%

74.5%

Card

iovascula

r M

ort

alit

y (

%)

Numbers at Risk

Standard Rx 179 121 85 62 46 27 17

TAVR 179 138 124 110 101 88 70

Months

HR [95% CI] = 0.41 [0.30, 0.56]

p (log rank) < 0.0001

24.1%

31.7%

33.1%

NNT = 4.1 pts

NNT = 3.2 pts

NNT = 3.0 pts

Standard Rx

TAVR

0%

20%

40%

60%

80%

100%

Months Numbers at Risk

Standard Rx 179 121 85 62 46 27 17

TAVR 179 138 124 110 101 88 70

0 6 12 18 24 30 36

All Cause Mortality (ITT) Landmark Analysis

30.7%

50.8%

17.8%

35.1%

19.3%

40.3%

All

Cause M

ort

alit

y (

%)

HR [95% CI] = 1.90 [1.05, 3.43]

p (log rank) = 0.03

HR [95% CI] = 2.03 [1.36, 3.04]

p (log rank) = 0.0005

HR [95% CI] = 0.53 [0.41, 0.68]

p (log rank) < 0.0001

∆ = 20.1% ∆ = 17.3% ∆ = 21.0%

NNT = 5.0 pts NNT = 5.8 pts NNT = 4.8 pts

Standard Rx

TAVR

Repeat Hospitalization (ITT)

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

53.9%

27.0%

72.5%

34.9%

75.7%

42.3%

71.6%

44.1%

88.0%

56.5%

93.1%

66.3%

Numbers at Risk

Standard Rx 179 86 49 30 19 11 7 179 86 49 30 19 11 7

TAVR 179 115 100 89 77 64 49 179 115 100 89 77 64 49

Months Months

Re

ho

sp

ita

liza

tio

n (

%)

Mo

rta

lity o

r R

eh

osp

ita

liza

tion

(%

)

Rehospitalization Mortality or Rehospitalization

Standard Rx

TAVR

33.4%

HR [95% CI] = 0.39 [0.28, 0.54]

p (log rank) < 0.0001

NNT = 3.7 pts

NNT = 2.7 pts

NNT = 3.0 pts NNT = 3.6 pts

NNT = 3.2 pts

NNT = 3.7 pts 37.6%

26.9%

26.8%

31.5%

27.5%

HR [95% CI] = 0.46 [0.36, 0.58]

p (log rank) < 0.0001

TAVR 944 [233-1096] Standard Rx 368 [147-1096] p <.0001 Days Alive Out of Hospital Median [IQR]

NYHA Class Over Time (ITT)

0%

20%

40%

60%

80%

100%

TAVR

179

Standard Rx

179

TAVR

173

Standard Rx

167

TAVR

173

Standard Rx

160

TAVR

165

Standard Rx

146

Dead

IV

III

II

I

Baseline 1 Year 2 Year 3 Year

p < 0.0001

N =

p = NS p < 0.0001 p < 0.0001

58.8%

91.1%

45.7%

76.9%

34.7%

59.3%

43.6% 45.3%

All Stroke (ITT)

0%

10%

20%

30%

40%

50%

0 6 12 18 24 30 36

5.5%

11.2%

5.5%

13.7%

5.5%

15.7% Str

oke (

%)

Months

HR [95% CI] = 2.77 [1.24, 6.19]

p (log rank) = 0.0094

∆ = 5.7%


NNT = 9.8 pts

∆ = 8.2% ∆ = 10.2%

Standard Rx

TAVR

Numbers at Risk

TAVR 179 128 116 105 96 82 65

Standard Rx 179 118 84 62 46 27 17

Stroke – Between year 2-3

ITT arm Age Days post

randomization Description Comorbidity

Procedure

related*

Device

related* Comments

TAVR 97 879 Ischemic Blood stream

infection,

Right carotid

stenosis

(80%)

No No Cerebellar infarct;

Linear echodensity on

mitral valve, Ao valve:

Mild AI

TAVR 87 837 Acute infarct

with surrounding

intraparenchymal

bleed

Atrial

Fibrillation

not on

warfarin

No No Cerebellar infarct/

hemorrhage;

Ao valve: Ok

*CEC adjudicated

Numbers at Risk

Standard Rx 179 118 84 62 46 27 17

TAVR 179 128 116 105 96 82 65

Mortality or Stroke (ITT)

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

51.3%

35.2%

45.8%

57.5%

68.0%

80.9%

Mort

alit

y o

r S

troke (

%)

Months

HR [95% CI] = 0.60 [0.46, 0.77]

p (log rank) < 0.0001

16.1%

22.2%

23.4%

NNT = 6.2 pts

NNT = 4.5 pts

NNT = 4.3 pts

Standard Rx

TAVR

Mean Gradient & Valve Area

44.2

10.2 11.0 10.9 10.8 11.3

0.6

1.5

1.6 1.6 1.6 1.5

0

0.5

1

1.5

2

2.5

0

10

20

30

40

50

60

70

Baseline

159

30 Day

137

6 Month

96

1 Year

86

2 Year

70

3 Year

43

Mean G

radie

nt

(mm

Hg)

EOA

Mean Gradient

Valv

e A

rea (

cm

²)

N =

Error bars = ± 1 Std Dev

Paravalvular Leak

0%

20%

40%

60%

80%

100%

30 Day

44

6 Month

45

1 Year

44

2 Year

45

3 Year

46

Valve Implant Patients (restricted to patients with 3 year values)

Severe

Moderate

Mild

Trace

None

Perc

ent of

evalu

able

echos

N =

Numbers at Risk

Mild 78 61 54 47 43 36 26

Mod.-Severe 23 17 16 15 13 12 9

None-Trace 64 51 47 43 41 37 29

Mortality Stratified by Paravalvular Leak Valve Implant Patients

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

26.6%

30.8%

30.4%

34.4%

43.5%

44.9%

45.6%

55.7%

57.0%

None-Trace

Moderate-Severe

Mild

Mort

alit

y (

%)

Months

HR [95% CI] = 1.09 [0.82, 1.45]

p (log rank) = 0.8059

Mortality Stratified by STS Score (ITT)

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

Mo

rta

lity (

%)

Months Months Months

STS: 0 - 4.9 STS: 5.0 - 14.9 STS ≥ 15

Standard Rx

TAVR

∆ = 66.8%


∆ = 20.8% ∆ = 22.3%

Numbers at Risk

Standard Rx 12 8 7 6 5 3 0 123 86 61 44 33 19 13 43 27 17 12 8 5 4

TAVR 28 26 25 24 21 19 16 113 84 79 70 65 55 44 38 28 20 16 15 14 10

100%

33.2%

86.6%

65.8% 55.2%

77.5%

Non-Randomized Continued Access

Cohort B: 235 Patients

Randomized PARTNER

Cohort A: 699 Patients

May 2007 – September 2009

PARTNER Secondary Analysis Pooled Cohort (ITT)

Randomized PARTNER

Cohort B: 358 Patients

2007 2008 2009

Randomized PARTNER

Cohort B Randomized Continued Access: 91 Patients

May 2007 – March 2009 March 2009 – September 2009

September 2009 –

January 2012

Non-Randomized Continued Access

Cohort A: 1,833 Patients

September 2009 –

July 2011

Primary Outcome (Composite) All Cause Mortality

Conclusions (1)

• At 3 years follow-up benefits of TAVR were

sustained as measured by:

– All cause mortality

– Cardiovascular mortality

– Repeat hospitalization

– Functional status

• Valve durability was demonstrated with no increase

in transvalvular gradient or attrition of valve area.

• Detailed analysis of all randomized inoperable

patients showed consistent results for all outcomes.

Conclusions (2)

• Survival benefit of TAVR is dependent on the

presence of comorbid illness.

• Without TAVR, mortality is similar irrespective

of comorbid illness.

Clinical Implications

• Three year data continue to support the role of

TAVR as the standard-of-care for symptomatic

patients with aortic stenosis who are not surgical

candidates.

• These data underscore the importance of patient

selection before TAVR and the need for

aggressive management of illnesses after TAVR.

Thank You to the Dedicated Study Teams at All PARTNER Investigational Sites

Backup Slides

n = 358

Randomized Inoperable

n = 179

TAVR

n = 179

Standard Therapy



101/102 patients* 99.0% followed at 2 Yr


Study Flow Inoperable Cohort – Crossover Patients Followed in Standard Therapy Arm

• *One TAVR patient was alive and censored prior to the window

• **Two TAVR patients were alive and censored prior to the window (including the one in the same status at 2 years); one TAVR patient withdrew between 2 and 3 years

• No patients were lost to follow-up

80/82 patients** 97.6% followed at 3 Yr


Survival of Crossover Patients

1-2 year n = 11

2-3 year n = 9

Alive, n (%) Dead, n (%) Alive, n (%) Dead, n (%)

8 (72%) 3 (28%) 7 (77%) 2 (22%)

Crossover Follow-up (days) Crossover Follow-up (days)

522 ± 129 323 ± 248 469 ± 178 110 ± 11

• No patients crossed over after three years

Survival of Crossover Patients

Crossover Patients n 30 Day Mortality

Events (%)

1 Year Mortality

Events (%)

Last Follow-Up Mortality

Events (%)

1-2 year 11 0 (0) 1 (9) 3 (27)

2-3 year 9 0 (0) 2 (22) 2 (22)

All 20 0 (0) 3 (15) 5 (20)

Follow-up of surviving patients = 497 ± 150 days

Cardiovascular Mortality (ITT) Landmark Analysis

0%

20%

40%

60%

80%

100%

20.5%

44.6%

12.7%

32.1%

15.1%

32.2%

Ca

rdio

va

scu

lar

Mo

rta

lity (

%)

Numbers at Risk

Standard Rx 179 121 85 62 46 27 17

TAVR 179 138 124 110 101 88 70

HR [95% CI] = 0.41 [0.30, 0.56]

p (log rank) < 0.0001

HR [95% CI] = 2.48 [1.56, 3.95]

p (log rank) < 0.0001

HR [95% CI] = 2.09 [1.05, 4.16]

p (log rank) = 0.0314

∆ = 24.1% ∆ = 19.4% ∆ = 17.1%


0 6 12 18 24 30 36

Months

Standard Rx

TAVR

NYHA Class Over Time (ITT) Survivors

0%

20%

40%

60%

80%

100%

TAVR

179

Standard Rx

179

TAVR

118

Standard Rx

79

TAVR

96

Standard Rx

41

TAVR

69

Standard Rx

14

IV

III

II

I


N =

29.0%

50.0%

17.7%

56.1%

23.7%

60.8%

92.2% 93.9%

p = NS p = NS p < 0.0001 p < 0.0001

Adverse Events Between 2 and 3 years (ITT)

3 Year n = 179

2-3 Year n = 179

Outcome TAVR Standard Rx TAVR Standard Rx

Myocardial infarction

All, % (n) 4.0 (4) 2.5 (2) 2.4 (2) 0 (0)

Acute kidney injury

Renal failure (CEC), % (n) 3.2 (5) 11.1 (10) 0 (0) 3.7 (1)

Bleeding – major, % (n) 32.0 (51) 32.9 (28) 3.4 (3) 13.0 (3)

Cardiac re-intervention

BAV, % (n) 3.8 (5) 85.3 (140) 1.0 (1) 4.7 (2)

TAVR, % (n) 1.7 (3) 4.5 (4) 0 (0) 0 (0)

AVR, % (n) 0.9 (1) 8.9 (11) 0 (0) 0 (0)

Endocarditis, % (n) 2.3 (3) 0.8 (0) 0 (0) 0 (0)

New pacemaker, % (n) 7.6 (11) 8.6 (14) 1.2 (1) 0 (0)

Numbers at Risk

Mild-Severe 101 78 70 62 56 48 35

None-Trace 64 51 47 43 41 37 29

Mortality Stratified by Paravalvular Leak Valve Implant Patients

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

30.7%

26.6%

44.6%

34.4%

56.0%

45.6%

Months

Mort

alit

y (

%)

HR [95% CI] = 1.15 [0.76, 1.74]

p (log rank) = 0.5114

∆ = 10.4%

NNT = 24.4 pts

NNT = 9.8 pts

NNT = 9.6 pts

∆ = 4.1%

∆ = 10.2%

Mild-Severe

None-Trace

Echo Analysis PV Leak Changes 30 Days Compared to 3 Years

16.6% Progressed 31.0% Improved 52.4% Unchanged

3 Year

30 Day None Trace Mild Moderate

None 7 3 0 0

Trace 5 5 2 0

Mild 5 1 11 2

Moderate 0 1 2 0

Of the 42 patients alive with data at 3 years:

Patients With Data at Both Time Points

Numbers at Risk

> 15 38 28 20 16 15 14 10

5 - 15 113 84 79 70 65 55 44

< 5 28 26 25 24 21 19 16

TAVR Mortality Stratified by STS Score (ITT)

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

10.7%

47.4%

30.1%

21.6%

60.5%

42.5%

33.2%

65.8%

55.2%

Mort

alit

y (

%)

5 - 15

> 15

< 5

Months

p (log rank) = 0.0503

Patient Characteristics (1) Pooled


Standard Rx n = 220

p value

Age – yr (SD) 83.2 (8.5) 83.0 (8.5) 0.8

Male sex (%) 48.5 47.7 0.9

STS Score (SD) 12.2 (5.4) 11.4 (6.0) 0.1

NYHA III or IV (%) 94.3 92.7 0.6

CAD (%) 73.8 65.9 0.08

Prior MI (%) 28.4 22.3 0.1

Prior CABG (%) 42.4 31.8 0.02

Prior PCI (%) 22.7 25.9 0.4

Prior BAV (%) 21.4 13.6 0.04

CVD (%) 25.8 26.8 0.6

Patient Characteristics (2) Pooled


Standard Rx n = 220

p value

PVD (%) 24.9 30.0 0.2

COPD

Any (%)

O2 dependent (%)

72.9

24.7

64.3

22.0

0.1

0.8

Creatinine > 2 mg/dL (%) 8.8 5.5 0.2

Atrial fibrillation (%) 26.6 20.8 0.2

Perm. pacemaker (%) 19.7 20.5 0.9

Pulmonary HTN (%) 50.7 47.7 0.6

Frailty (%) 25.6 17.8 0.1

Porcelain aorta (%) 11.8 18.6 0.049

Chest wall radiation (%) 7.9 7.7 1.0

Chest wall deformity (%) 6.1 7.7 0.6

Liver disease (%) 3.5 5.0 0.4

Primary Outcome (Composite) Functional Status

Primary Outcome (Composite) Mean Gradient & AVA

Univariate and Multivariate Predictors of Mortality after TAVR

Univariate Predictors

Hazard Ratio p value

BMI > 26 0.58 (0.39 – 0.86) 0.007

Peripheral Vascular Disease 1.67 (1.13 – 2.47) 0.01

Oxygen dependent COPD 1.62 (1.05 -2.49) 0.03

History of Stroke or TIA 3.19 (1.28 – 7.92) 0.01

History of CABG 0.64 (0.42 – 0.98) 0.04

Multivariate Predictors

Hazard Ratio p value

BMI > 26 0.47 (0.31 – 0.70) 0.02

Peripheral Vascular Disease 1.59 (1.07 – 2.38) 0.02

Oxygen dependent COPD 1.83 (1.17 – 2.85) 0.008

Moderate or Severe MR 0.56 (0.33 – 0.94) 0.03

Pooled Randomized

Numbers at Risk

Standard Rx 229 163 118 77 56 33 17

TAVR 220 169 151 133 117 103 70

All Cause Mortality (ITT) Pooled Randomized Crossover Patients Censored at Crossover

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

31.4%

45.5%

44.8%

64.3%

54.9%

78.0%

All

Ca

use M

ort

alit

y (

%)

Months

HR [95% CI] = 0.60 [0.47, 0.76]

p (log rank) < 0.0001

14.1%

19.5%

23.1%

NNT = 7.1 pts

NNT = 5.1 pts

NNT = 4.3 pts

Standard Rx

TAVR

Cardiovascular Mortality (ITT) Pooled Randomized Crossover Patients Censored at Crossover

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

21.0%

38.4%

31.2%

56.9%

41.4%

70.2%

Card

iovascula

r M

ort

alit

y (

%)

Numbers at Risk

Standard Rx 229 163 118 77 56 33 17

TAVR 220 169 151 133 117 103 70

Months

HR [95% CI] = 0.47 [0.36, 0.63]

p (log rank) < 0.0001

17.4%

25.7%

28.8%

NNT = 5.7 pts

NNT = 3.9 pts

NNT = 3.5 pts

Standard Rx

TAVR

All Cause Mortality (ITT) Pooled Randomized – Landmark Analysis

0%

20%

40%

60%

80%

100%

31.4%

45.5%

19.6%

34.4%

18.3%

38.5%

All

Cause M

ort

alit

y (

%)

Months

Numbers at Risk

Standard

Rx 229 163 118 77 56 33 17

TAVR 220 169 151 133 117 103 70

HR [95% CI] = 1.94 [1.09, 3.45]

p (log rank) = 0.0223

HR [95% CI] = 1.94 [1.33, 2.83]

p (log rank) = 0.0004

HR [95% CI] = 0.60 [0.47, 0.76]

p (log rank) < 0.0001

∆ = 14.1% ∆ = 14.8% ∆ = 20.2%


Standard Rx

TAVR

0 6 12 18 24 30 36

Cardiovascular Mortality (ITT) Pooled Randomized – Landmark Analysis

0%

20%

40%

60%

80%

100%

21.0%

38.4%

12.9%

30.1%

14.8%

30.9%

Ca

rdio

va

scu

lar

Mo

rta

lity (

%)

Months

Numbers at Risk

Standard

Rx 229 163 118 77 56 33 17

TAVR 220 169 151 133 117 103 70

∆ = 17.4% ∆ = 17.2% ∆ = 16.1%


0 6 12 18 24 30 36

HR [95% CI] = 0.47 [0.36, 0.63]

p (log rank) < 0.0001

HR [95% CI] = 2.44 [1.57, 3.78]

p (log rank) < 0.0001

HR [95% CI] = 2.13 [1.09, 4.16]

p (log rank) = 0.0229

Standard Rx

TAVR

Repeat Hospitalization (ITT) Pooled Randomized

Numbers at Risk

Standard Rx 229 120 74 43 26 14 7 229 120 74 43 26 14 7

TAVR 220 142 122 106 87 73 49 220 142 122 106 87 73 49

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

47.4%

26.4%

66.5%

35.0%

71.4%

42.4%

65.4%

44.6%

83.8%

58.5%

90.6%

67.5%

HR [95% CI] = 0.45 [0.33, 0.61]

p (log rank) < 0.0001

29.0%

NNT = 4.8 pts

NNT = 3.2 pts


NNT = 4.0 pts

NNT = 4.3 pts 31.5%

21.0%

23.1%

25.3%

20.8%

HR [95% CI] = 0.54 [0.44, 0.68]

p (log rank) < 0.0001

Rehospitalization Mortality or Rehospitalization

Re

ho

sp

ita

liza

tio

n (

%)

Mo

rta

lity o

r R

eh

osp

ita

liza

tion

(%

)

Months Months

Standard Rx

TAVR

NYHA Class Over Time (ITT) Pooled Randomized

0%

20%

40%

60%

80%

100%

TAVR

220

Standard Rx

229

TAVR

214

Standard Rx

213

TAVR

209

Standard Rx

187

TAVR

201

Standard Rx

169

Dead

IV

III

II

I


p < 0.0001 p = NS p < 0.0001 p < 0.0001

60.2%

90.5%

47.9%

75.9%

35.1%

54.9%

44.1% 46.7%

N =

NYHA Class Over Time (ITT) Pooled Randomized (Survivors)

0%

20%

40%

60%

80%

100%

TAVR

220

Standard Rx

229

TAVR

145

Standard Rx

113

TAVR

111

Standard Rx

49

TAVR

81

Standard Rx

17

IV

III

II

I


25.9%

41.2%

18.0%

53.1%

23.4%

61.9%

92.7% 94.3%

p = NS p = NS

N =

p < 0.0001 p < 0.0001

All Stroke (ITT) Pooled Randomized

Numbers at Risk

Standard Rx 229 160 117 77 56 33 17

TAVR 220 158 142 127 112 97 65

0%

10%

20%

30%

40%

50%

0 6 12 18 24 30 36

4.2%

10.5%

4.2%

12.7%

4.2%

14.4% Str

oke (

%)

Months

HR [95% CI] = 3.33 [1.51, 7.35]

p (log rank) = 0.0016

∆ = 6.3%


NNT = 9.8 pts

∆ = 8.5% ∆ = 10.2%

Standard Rx

TAVR

Mortality or Stroke (ITT) Pooled Randomized

Numbers at Risk

Standard Rx 229 160 117 77 56 33 17

TAVR 220 158 142 127 112 97 65

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

45.9%

35.5%

47.1%

57.8%

64.2%

78.0%

Mort

alit

y o

r S

troke (

%)

Months

HR [95% CI] = 0.67 [0.53, 0.85]

p (log rank) = 0.0008

10.4%

17.1%

20.2%

NNT = 9.6 pts

NNT = 5.8 pts

NNT = 5.0 pts

Standard Rx

TAVR

Mean Gradient & Valve Area Pooled Randomized

43.6

10.2 10.7 10.7 10.9 11.6

0.6

1.6

1.6 1.6 1.5 1.5

0

0.5

1

1.5

2

2.5

0

10

20

30

40

50

60

70

Baseline

196

30 Day

168

6 Month

120

1 Year

107

2 Year

82

3 Year

49

Mean G

radie

nt

(mm

Hg)

EOA

Mean Gradient

Valv

e A

rea (

cm

²)

N =

Error bars = ± 1 Std Dev

Paravalvular Leak Pooled Randomized

0%

20%

40%

60%

80%

100%

30 Day

50

6 Month

50

1 Year

50

2 Year

51

3 Year

52

Valve Implant Patients (restricted to patients with 3 year values)

Severe

Moderate

Mild

Trace

None

Perc

ent of

evalu

able

echos

N =

Mortality Stratified by Paravalvular Leak (ITT) Pooled Randomized – Valve Implant Patients

Numbers at Risk

Mild-Severe 123 95 83 72 62 54 35

None-Trace 81 65 61 55 51 46 29

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

32.5%

24.7%

48.1%

33.6%

59.0%

43.0%

Months

Mort

alit

y (

%)

HR [95% CI] = 1.32 [0.90, 1.94]

p (log rank) = 0.1483

∆ = 16.0%

NNT = 12.8 pts

NNT = 6.9 pts

NNT = 6.3 pts

∆ = 7.8%

∆ = 14.5%

Mild-Severe

None-Trace

Mortality Stratified by Paravalvular Leak (ITT) Pooled Randomized – Valve Implant Patients

Numbers at Risk

Mod.-Severe 33 25 22 20 15 14 9

Mild 90 70 61 52 47 40 26

None-Trace 81 65 61 55 51 46 29

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

24.7%

33.3%

32.2%

33.6%

47.8%

49.5%

43.0%

60.4%

58.7%

Mort

alit

y (

%)

Months

HR [95% CI] = 1.18 [0.92, 1.51]

p (log rank) = 0.3517

None-Trace

Mild

Moderate-Severe

Mortality Stratified by STS Score (ITT) Pooled Randomized

Numbers at Risk

> 15 47 33 25 20 17 16 10

5 - 15 141 106 97 85 77 66 44

< 5 32 30 29 28 23 21 16

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

9.4%

46.8%

31.2%

25.4%

63.8%

42.8%

35.9%

68.1%

54.8%

Mort

alit

y (

%)

Months

p (log rank) = 0.0168

5 - 15

> 15

< 5

Mortality Stratified by STS Score (ITT) Pooled Randomized

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36

Mo

rta

lity (

%)

Months Months Months

STS: 0 - 4.9 STS: 5.0 - 14.9 STS ≥ 15

∆ = 64.1%


∆ = 15.0% ∆ = 19.6%

Numbers at Risk

Standard Rx 16 11 9 6 5 3 0 154 113 84 56 41 24 13 58 39 25 15 10 6 4

TAVR 32 30 29 28 23 21 16 141 106 97 85 77 66 44 47 33 25 20 17 16 10

100%

35.9%

83.1%

68.1% 54.8%

74.4%

Standard Rx

TAVR

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