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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
• Samir Kapadia – No financial disclosures
– Member of PARTNER Trial steering committee
• Murat Tuzcu– No financial disclosures
– Member of PARTNER Trial executive committee
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 = 358Inoperable
StandardTherapyn = 179
ASSESSMENT: Transfemoral
Access
TF TAVRn = 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 = 358Randomized Inoperable
n = 179TAVR
n = 179Standard Therapy
124/124 patients100% followed at 1 Yr
124/124 patients100% followed at 1 Yr
85/85 patients100% followed at 1 Yr
85/85 patients100% followed at 1 Yr
101/102 patients*99.0% followed at 2 Yr
101/102 patients*99.0% followed at 2 Yr
46/46 patients100% followed at 2 Yr
46/46 patients100% followed at 2 Yr
Study FlowInoperable 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
80/82 patients**97.6% followed at 3 Yr
19/19 patients100% followed at 3 Yr
19/19 patients100% 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 TAVRn = 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
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
Note: Same as previously presented at TCT 2010 and published in the NEJM manuscript.
Patient Characteristics (2)
Characteristic TAVRn = 179
Standard Rxn = 179
p value
PVD (%) 30.3 25.1 0.29
COPD Any (%) O2 dependent (%)
41.321.2
52.525.7
0.040.38
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.
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
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
30.7%
50.8%
43.0%
68.0%
54.1%
80.9%
All
Cau
se M
orta
lity
(%)
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 RxTAVR
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
Cardiovascular Mortality (ITT)Crossover Patients Censored at Crossover
20.5%
44.6%
30.7%
62.4%
41.4%
74.5%
Car
diov
ascu
lar
Mor
talit
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 RxTAVR
0%
20%
40%
60%
80%
100%
MonthsNumbers 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
Cau
se M
orta
lity
(%)
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 RxTAVR
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 360%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
Repeat Hospitalization (ITT)
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 7TAVR 179 115 100 89 77 64 49 179 115 100 89 77 64 49
Months Months
Reh
ospi
taliz
atio
n (%
)
Mor
talit
y or
Reh
ospi
taliz
atio
n (%
)
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 pts37.6%
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 <.0001Days Alive Out of Hospital Median [IQR]
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
NYHA Class Over Time (ITT)
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%
0%
10%
20%
30%
40%
50%
0 6 12 18 24 30 36
All Stroke (ITT)
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 = 17.5 ptsNNT = 12.2 pts
NNT = 9.8 pts
∆ = 8.2%∆ = 10.2%
Standard RxTAVR
Numbers at Risk
TAVR 179 128 116 105 96 82 65
Standard Rx 179 118 84 62 46 27 17
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
Numbers at Risk
Standard Rx 179 118 84 62 46 27 17
TAVR 179 128 116 105 96 82 65
Mortality or Stroke (ITT)
51.3%
35.2%
45.8%
57.5%
68.0%
80.9%
Mor
talit
y or
Str
oke
(%)
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 RxTAVR
44.2
10.211.0 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 Gradient & Valve AreaM
ean
Gra
dien
t (m
mH
g)
EOAMean Gradient
Val
ve A
rea
(cm
²)
N =
Error bars = ± 1 Std Dev
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
Paravalvular LeakP
erce
nt o
f eva
luab
le e
chos
N =
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 360%
20%
40%
60%
80%
100%
0 6 12 18 24 30 360%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
Mortality Stratified by STS Score (ITT)
Mor
talit
y (%
)
Months Months Months
STS: 0 - 4.9 STS: 5.0 - 14.9 STS ≥ 15
Standard Rx
TAVR
∆ = 66.8%
NNT = 1.5 pts NNT = 4.5 pts NNT = 4.8 pts
∆ = 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 BRandomized 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 = 358Randomized Inoperable
n = 179TAVR
n = 179Standard Therapy
124/124 patients100% followed at 1 Yr
124/124 patients100% followed at 1 Yr
85/85 patients100% followed at 1 Yr
85/85 patients100% followed at 1 Yr
101/102 patients*99.0% followed at 2 Yr
101/102 patients*99.0% followed at 2 Yr
56/56 patients100% followed at 2 Yr
56/56 patients100% followed at 2 Yr
Study FlowInoperable 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
80/82 patients**97.6% followed at 3 Yr
34/34 patients100% followed at 3 Yr
34/34 patients100% followed at 3 Yr
Survival of Crossover Patients
1-2 yearn = 11
2-3 yearn = 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 MortalityEvents (%)
1 Year MortalityEvents (%)
Last Follow-Up MortalityEvents (%)
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
0%
20%
40%
60%
80%
100%
Cardiovascular Mortality (ITT)Landmark Analysis
20.5%
44.6%
12.7%
32.1%
15.1%
32.2%
Car
diov
ascu
lar
Mor
talit
y (%
)
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%
NNT = 4.1 pts NNT = 5.2 pts NNT = 5.8 pts
0 6 12 18 24 30 36
Months
Standard RxTAVR
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
NYHA Class Over Time (ITT)Survivors
Baseline 1 Year 2 Year 3 Year
N =
29.0%
50.0%
17.7%
56.1%
23.7%
60.8%
92.2% 93.9%
p = NSp = NS p < 0.0001 p < 0.0001
Adverse EventsBetween 2 and 3 years (ITT)
3 Yearn = 179
2-3 Yearn = 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)
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
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
30.7%
26.6%
44.6%
34.4%
56.0%
45.6%
Months
Mor
talit
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-SevereNone-Trace
Echo Analysis PV Leak Changes 30 Days Compared to 3 Years
16.0% Progressed31.8% Improved 52.3% 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 44 patients alive with data at both 30 days and 3 years:
Patients With Data at Both Time Points
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
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)
10.7%
47.4%
30.1%
21.6%
60.5%
42.5%
33.2%
65.8%
55.2%
Mor
talit
y (%
)
5 - 15> 15
< 5
Months
p (log rank) = 0.0503
Patient Characteristics (1)Pooled
Characteristic TAVRn = 229
Standard Rxn = 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
Characteristic TAVRn = 229
Standard Rxn = 220
p value
PVD (%) 24.9 30.0 0.2
COPD Any (%) O2 dependent (%)
72.924.7
64.322.0
0.10.8
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
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
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 RandomizedCrossover Patients Censored at Crossover
31.4%
45.5%
44.8%
64.3%
54.9%
78.0%
All
Cau
se M
orta
lity
(%)
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 RxTAVR
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
Cardiovascular Mortality (ITT)Pooled RandomizedCrossover Patients Censored at Crossover
21.0%
38.4%
31.2%
56.9%
41.4%
70.2%
Car
diov
ascu
lar
Mor
talit
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 RxTAVR
0%
20%
40%
60%
80%
100%
All Cause Mortality (ITT)Pooled Randomized – Landmark Analysis
31.4%
45.5%
19.6%
34.4%
18.3%
38.5%
All
Cau
se M
orta
lity
(%)
MonthsNumbers 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%
NNT = 7.1 pts NNT = 6.8 pts NNT = 5.0 pts
Standard RxTAVR
0 6 12 18 24 30 36
0%
20%
40%
60%
80%
100%
Cardiovascular Mortality (ITT)Pooled Randomized – Landmark Analysis
21.0%
38.4%
12.9%
30.1%
14.8%
30.9%
Car
diov
ascu
lar
Mor
talit
y (%
)
MonthsNumbers 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%
NNT = 5.7 pts NNT = 5.8 pts NNT = 6.2 pts
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 RxTAVR
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 360%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
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
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 = 3.4 pts NNT = 4.8 pts
NNT = 4.0 pts
NNT = 4.3 pts31.5%
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
Reh
ospi
taliz
atio
n (%
)
Mor
talit
y or
Reh
ospi
taliz
atio
n (%
)
Months Months
Standard Rx
TAVR
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
NYHA Class Over Time (ITT)Pooled Randomized
Baseline 1 Year 2 Year 3 Year
p < 0.0001p = NS p < 0.0001 p < 0.0001
60.2%
90.5%
47.9%
75.9%
35.1%
54.9%
44.1% 46.7%
N =
0%
20%
40%
60%
80%
100%
TAVR
220
StandardRx
229
TAVR
145
Standard Rx
113
TAVR
111
Standard Rx
49
TAVR
81
Standard Rx
17
IV
III
II
I
NYHA Class Over Time (ITT)Pooled Randomized (Survivors)
Baseline 1 Year 2 Year 3 Year
25.9%
41.2%
18.0%
53.1%
23.4%
61.9%
92.7% 94.3%
p = NSp = NS
N =
p < 0.0001 p < 0.0001
0%
10%
20%
30%
40%
50%
0 6 12 18 24 30 36
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
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 = 15.9 ptsNNT = 11.8 pts
NNT = 9.8 pts
∆ = 8.5% ∆ = 10.2%
Standard RxTAVR
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
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
45.9%
35.5%
47.1%
57.8%
64.2%
78.0%
Mor
talit
y or
Str
oke
(%)
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 RxTAVR
Months
43.6
10.210.7 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 Gradient & Valve AreaPooled Randomized
Mea
n G
radi
ent (
mm
Hg)
EOAMean Gradient
Val
ve A
rea
(cm
²)
N =
Error bars = ± 1 Std Dev
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
Paravalvular LeakPooled Randomized
Per
cent
of e
valu
able
ech
os
N =
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
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
32.5%
24.7%
48.1%
33.6%
59.0%
43.0%
Months
Mor
talit
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-SevereNone-Trace
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
Mortality Stratified by Paravalvular Leak (ITT)Pooled Randomized – Valve Implant Patients
Numbers at Risk
Mod.-Severe 33 25 22 20 15 14 9Mild 90 70 61 52 47 40 26None-Trace 81 65 61 55 51 46 29
24.7%
33.3%
32.2%
33.6%
47.8%
49.5%
43.0%
60.4%
58.7%
Mor
talit
y (%
)
Months
HR [95% CI] = 1.18 [0.92, 1.51]p (log rank) = 0.3517
None-TraceMildModerate-Severe
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
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
9.4%
46.8%
31.2%25.4%
63.8%
42.8%
35.9%
68.1%
54.8%
Mor
talit
y (%
)
Months
p (log rank) = 0.01685 - 15> 15
< 5
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 360%
20%
40%
60%
80%
100%
0 6 12 18 24 30 360%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
Mortality Stratified by STS Score (ITT)Pooled Randomized
Mor
talit
y (%
)
Months Months Months
STS: 0 - 4.9 STS: 5.0 - 14.9 STS ≥ 15
∆ = 64.1%
NNT = 1.6 pts NNT = 5.1 pts NNT = 6.7 pts
∆ = 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
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
0%
20%
40%
60%
80%
100%
0 6 12 18 24 30 36
Numbers at Risk
Mild 78 61 54 47 43 36 26Mod.-Severe 23 17 16 15 13 12 9None-Trace 64 51 47 43 41 37 29
Mortality Stratified by Paravalvular LeakValve Implant Patients
26.6%
30.8%
30.4%
34.4%
43.5%
44.9%
45.6%
55.7%
57.0%
None-TraceModerate-SevereMild
Mor
talit
y (%
)
Months
HR [95% CI] = 1.09 [0.82, 1.45]p (log rank) = 0.8059