Transcript Five-Year Outcomes of Transcatheter Aortic Valve

Five-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
TCT 2014 | September 13, 2014
Background
• Transcatheter aortic valve
replacement (TAVR) is the
recommended treatment for
“inoperable” patients with
severe aortic stenosis (AS).
• Long term clinical benefit
and valve performance in
this population remain
unknown.
PARTNER Study Design
Symptomatic Severe Aortic Stenosis
Inoperable
Severe Symptomatic AS with
AVA< 0.8 cm2 (EOA index
< 0.5 cm2/m2), and mean
gradient > 40 mmHg
or jet velocity > 4.0 m/s
N = 358
ASSESSMENT:
Transfemoral
Access
1:1 Randomization
TF TAVR
n = 179
VS
Inoperable defined as risk of
death or serious irreversible
morbidity of AVR as assessed
by cardiologist and two
surgeons exceeding 50%.
Standard
Therapy
n = 179
Primary Endpoint: All-Cause Mortality
Over Length of Trial (Superiority)
• Primary endpoint evaluated when all patients reached one year follow-up.
• After primary endpoint analysis reached, patients were allowed to cross-over to TAVR.
Key End-Points for 5 Year Analysis
• All-Cause Mortality
• Cardiac Mortality
• Re-hospitalization
• Stroke
• NYHA functional class
• Echo-derived valve areas, transvalvular gradients,
and paravalvular leak.
• Mortality outcomes stratified by STS score,
paravalvular leak and age.
Study Flow
Inoperable Cohort
N = 358
Randomized Inoperable
N = 179
Standard Therapy
N = 179
TAVR
10 Patients Withdrew
85 / 85 patients
100% followed at 1 Yr
124 / 124 patients
100% followed at 1 Yr
Cross Over
11 pts
19 / 19 patients
100% followed at 3 Yrs
81 / 83 patients
97.6% followed at 3 Yrs
Cross Over
9 pts
6 / 6 patients
100% followed at 5 Yrs*
50 / 51 patients
98.0% followed at 5 Yrs*
* ± 2 months follow-up window
Patient Characteristics
TAVR
Standard Rx
N = 179
N = 179
83.1 ± 8.6
83.2 ± 8.3
0.95
45.8
46.9
0.92
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
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
Frailty (%)
18.1
28.0
0.09
Porcelain aorta (%)
19.0
11.2
0.05
Chest wall radiation (%)
8.9
8.4
1.00
Characteristic
Age – yr
Male sex (%)
STS Score
p-value
All-Cause Mortality (ITT)
Crossover Patients Censored at Crossover
Standard Rx (n = 179)
TAVR (n = 179)
93.6%
All-Cause Mortality (%)
80.9%
87.5%
68.0%
71.8%
50.8%
64.1%
53.9%
43.0%
30.7%
HR [95% CI] = 0.50 [0.39, 0.65]
p (log rank) < 0.0001
Months
* In an age and gender matched US population without comorbidities,
the mortality at 5 years is 40.5%.
Median Survival
11.1 Months
p (log rank) < 0.0001
29.7 Months
Months
All-Cause Mortality (ITT)
Landmark Analysis
Standard Rx (n = 179)
TAVR (n = 179)
HR [95% CI] = 0.50 [0.39, 0.65]
p (log rank) < 0.0001
All-Cause Mortality (%)
HR [95% CI] = 0.46 [0.32, 0.66]
p (log rank) < 0.0001
HR [95% CI] = 0.47 [0.24, 0.94]
p (log rank) = 0.028
66.7%
0-1 Year
1-3 Years
3-5 Years
61.1%
50.8%
0
6
12
38.9%
33.4%
30.7%
18
24
30
Months
36
42
48
54
60
Cardiovascular Mortality (ITT)
Crossover Patients Censored at Crossover
Standard Rx (n = 179)
TAVR (n = 179)
Cardiovascular Mortality (%)
85.9%
74.5%
80.6%
62.4%
44.6%
57.3%
47.6%
41.2%
30.7%
HR [95% CI] = 0.41 [0.31, 0.55]
p (log rank) < 0.0001
20.5%
Months
Causes of Death
Percent Patients
18% vs 34%
48% vs 33%
n=179
n=179
All-Cause Mortality
Stratified by STS Score (ITT)
STS < 5
STS 5-15
STS > 15
p (log rank) = 0.0012
p (log rank) = 0.0002
p (log rank) = 0.0749
Mortality (%)
100%
93.4%
93.3%
75.2%
73.7%
55.9%
Months
Standard Rx (n = 12)
Months
Standard Rx (n = 123)
Months
Standard Rx (n = 43)
TAVR (n = 28)
TAVR (n = 113)
TAVR (n = 38)
Cardiovascular Mortality
Stratified by STS Score (ITT)
STS < 5
STS 5-15
STS > 15
p (log rank) < 0.0001
p (log rank) < 0.0001
p (log rank) = 0.0098
100%
91.8%
82.4%
Mortality (%)
61.6%
57.8%
41.1%
Months
Standard Rx (n = 12)
Months
Standard Rx (n = 123)
Months
Standard Rx (n = 43)
TAVR (n = 28)
TAVR (n = 113)
TAVR (n = 38)
Repeat Hospitalization (ITT)
Standard Rx (n = 179)
TAVR (n = 179)
83.0%
87.3%
46.3%
47.6%
75.7%
Rehospitalization (%)
72.5%
53.9%
43.1%
34.9%
27.0%
HR [95% CI] = 0.40 [0.29, 0.55]
p (log rank) < 0.0001
Months
NYHA Class Over Time (ITT)
Survivors
p = NS
p = NS
p < 0.0001
p = NS
14.3%
23.7%
30.0%
40.0%
50.0%
60.8%
92.2%
93.9%
N=
Baseline
1 Year
3 Years
5 Years
Competing Risks Analysis (ITT)
Incidence (%)
Death and Stroke
14.6%
5.7%
Months
Percent of Evaluable Echocardiograms
Paravalvular Leak (AT)
N=
Mortality by Paravalvular Leak
All-Cause Mortality
Cardiovascular Mortality
None-Mild (n = 142)
None-Mild (n = 142)
Moderate-Severe (n = 23)
Moderate-Severe (n = 23)
78.3%
74.6%
69.2%
51.3%
p (log rank) = 0.510
p (log rank) = 0.043
Mean Gradient & Valve Area (AT)
EOA
Mean Gradient
Valve Area (cm²)
Mean Gradient (mmHg)
Error bars = ± 1 Std Dev
N=
159
86
70
44
31
15
163
91
71
46
31
15
Mean Gradient & Valve Area (AT)
Restricted to Patients with 5 Year Data
EOA
Mean Gradient
Valve Area (cm²)
Mean Gradient (mmHg)
Error bars = ± 1 Std Dev
N=
15
14
14
12
13
15
16
14
14
12
13
15
Subgroup Analysis
All-Cause Mortality
Overall (N=358)
Age < 85 (N=186)
Age ≥ 85 (N=172)
Male (N=166)
Female (N=192)
BMI ≤ 25 (N=170)
BMI > 25 (N=188)
STS ≤ 11 (N=170)
STS > 11 (N=187)
EF ≤ 55 (N=173)
EF > 55 (N=171)
Pulmonary Hypertension
No (N=136)
Yes (N=103)
Mod / Sev MR
No (N=261)
Yes (N=77)
Oxygen Dependent COPD
No (N=270)
Yes (N=88)
Prior CABG or PCI
No (N=182)
Yes (N=176)
Hazard Ratio [95% CI]
0.50
[0.39-0.65]
Interaction
p-value
0.46
0.56
0.46
0.55
0.58
0.44
0.52
0.53
0.47
0.61
[0.33-0.66]
[0.39-0.79]
[0.32-0.66]
[0.40-0.78]
[0.41-0.84]
[0.31-0.63]
[0.36-0.76]
[0.37-0.74]
[0.33-0.67]
[0.42-0.88]
0.56
0.51
[0.37-0.85]
[0.32-0.82]
0.87
0.58
0.30
[0.43-0.77]
[0.17-0.53]
0.03
0.46
0.68
[0.35-0.62]
[0.42-1.10]
0.14
0.55
0.46
[0.39-0.78]
[0.32-0.66]
0.27
0.40
0.34
0.71
0.65
0.09
TAVR Mortality Stratified by Age (ITT)
96.0%
91.8%
Mortality (%)
73.5%
70.4%
Months
Clinical Observations
• Mortality benefit was similar in elderly (>85 yr) patients
compared to those ≤85 years.
• Cardiovascular mortality and all-cause mortality benefit
was seen even in patients with high STS score.
• Patients with O2 dependent COPD may have less
mortality benefit.
• Beyond early procedural risk of stroke there was no
persistent risk over 5-year follow up.
• Moderate and severe paravalvular leak is associated with
higher cardiovascular mortality particularly in patients with
less comorbidities.
Main Conclusions
• At 5 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.
Thank You to the Dedicated
Study Teams at All PARTNER
Investigational Sites