SUPPLEMENTAL ONLINE-ONLY MATERIAL
Table 1. Categories of Deaths within Timeframes Stratified by Randomized Treatment
for PARTNER-A Patients
TF-TAVR
Timeframe
TA-TAVR
AVR
CV
Non-CV
Uncat
CV
Non-CV
Uncat
CV
Non-CV
Uncat
≤30 days
8
0
0
3
1
0
10
12
0
>30 days-≤6 months
6
13
1
5
7
4
16
27
10
>6 months-≤12 months
9
12
5
1
4
5
2
10
2
>12 months
10
14
12
1
7
8
18
11
21
Total
33
39
18
10
19
17
46
60
33
Key: AVR, surgical aortic valve replacement; CV, cardiovascular; Non-CV, non-cardiovascular; TA-TAVR,
transapical transcatheter aortic valve replacement; TF-TAVR, transfemoral transcatheter aortic valve
replacement; Uncat, uncategorizable.
Table 2. Categories of Deaths within Timeframes Stratified by Randomized
Treatment for PARTNER-B Patients
Standard Therapy
Timeframe
TF-TAVR
CV
Non-CV
Uncat
CV
Non-CV
Uncat
≤30 days
3
2
0
7
1
1
>30 days-≤6 months
29
5
15
15
15
2
>6 months-≤12 months
18
7
11
4
4
6
>12 months
17
7
21
14
12
21
Total
67
21
47
40
32
30
Key: CV, cardiovascular; Non-CV, non-cardiovascular; TF-TAVR, transfemoral transcatheter aortic valve
replacement; Uncat, uncategorizable.
Figure 1. Instantaneous risk of death after surgical aortic valve replacement
(AVR) stratified by pre-randomization assessment as to suitability for a
transfemoral (TF, light red) or transapical (TA, dark red) approach. Overlap of
68% dashed confidence bands indicates that these 2 subgroups can be pooled.
Figure 2. Estimated lifetime gained by TF-TAVR over TA-TAVR. This represents
the integrated difference between respective survival curves in Figure 1B. Dashed
lines form a 90% confidence band.
Figure 3. Estimated lifetime gained by AVR over TA-TAVR. This represents the
integrated difference between respective survival curves in Figure 1B. Dashed
lines form a 90% confidence band.
Figure 4. Mortality after randomization in all PARTNER-A and B groups, with, for
reference, a series of nearly super-imposable dash-dot-dash lines representing
risk of death in an age-sex-race–matched US population.
Key: PARTNER-A: A-AVR, surgical aortic valve replacement (red); A-TA-TAVR,
transapical transcatheter aortic valve replacement (blue); A-TF-TAVR,
transfemoral TAVR (green). PARTNER-B: B-Standard Therapy (pink); B-TFTAVR, transfemoral TAVR (purple).
A. Instantaneous risk of death stratified by group.
B. Survival stratified by group. Each symbol represents a death and vertical bars
68% confidence limits (CL) equivalent to 1 standard error. Solid lines represent
parametric survival estimates.
Figure 5. Composite instantaneous risk of cardiovascular, non-cardiovascular,
and uncategorizable death in PARTNER-A treatment groups. Solid lines are
point estimates enclosed within dashed 68% confidence bands.
A. Transfemoral transcatheter aortic valve replacement.
B. Transapical transcatheter aortic valve replacement.
C. Surgical aortic valve replacement.
Figure 6. Composite instantaneous risk of cardiovascular, non-cardiovascular,
and uncategorizable death in PARTNER-B treatment groups. Solid lines are
point estimates enclosed within dashed 68% confidence bands.
A. Transfemoral transcatheter aortic valve replacement.
B. Standard therapy.
Figure 7. Composite instantaneous risk of cardiovascular and noncardiovascular death in PARTNER-A and B.
Key: PARTNER-A: A-AVR, surgical aortic valve replacement (red); A-TA-TAVR,
transapical transcatheter aortic valve replacement (blue); A-TF-TAVR,
transfemoral TAVR (green). PARTNER-B: B-Standard Therapy (pink); B-TFTAVR, transfemoral TAVR (purple).
A. Instantaneous risk of cardiovascular death.
B. Instantaneous risk of non-cardiovascular death.
Figure 8. Competing risks of cardiovascular, non-cardiovascular, and
uncategorizable death after transcatheter aortic valve replacement (TAVR) by the
transfemoral (TF) or transapical (TA) approach, surgical aortic valve replacement
(AVR), or standard therapy in PARTNER-A and B. Each symbol represents a
death and vertical bars 68% confidence limits (CL) equivalent to 1 standard
error. Solid lines enclosed within dashed 68% confidence bands represent
parametric survival estimates.
A. Full competing risk analysis for TF-TAVR in PARTNER-A. Patients are initially
all in the “Survival” category. Thereafter, patients can experience cardiovascular,
non-cardiovascular, or uncategorizable death, and these result in decrement in
survival across time. At a given time, all estimates of necessity add to 100%. In
subsequent graphs, we depict only the 3 categories of death, but each has a
corresponding survival curve.
B. Competing modes of death after TF-TAVR in PARTNER-A on expanded
vertical axis scale, with the initial category of survival suppressed.
C. Competing modes of death after TA-TAVR in PARTNER-A on expanded
vertical axis scale, with the initial category of survival suppressed.
D. Competing modes of death after AVR in PARTNER-A on expanded vertical
axis scale, with the initial category of survival suppressed.
E. Competing modes of death after TF-TAVR in PARTNER-B on expanded
vertical axis scale, with the initial category of survival suppressed.
F. Competing modes of death after standard therapy in PARTNER-B on
expanded vertical axis scale, with the initial category of survival suppressed.
Appendix. Fate of As-Treated Patients in PARTNER-A
Forty-two patients did not undergo aortic valve replacement (AVR) in PARTNER-A,
38 randomized to surgical AVR and 4 to transcatheter AVR (TAVR). Reasons
included refusal of treatment, withdrawal for medical reasons, and death before
treatment (Figure E9). Risk of pre-treatment mortality peaked by 2 months after
randomization (Figure E10A), and by 6 months, estimated survival without treatment
was 76% (Figure E10B). Mortality before treatment was higher in the AVR group due,
in part, to a longer average interval from randomization to procedure (Figure E11).
Unlike intent-to-treat analyses, the hazard functions for as-treated patients are
highest immediately after the procedure (Figure 12A); however, relationships among
stratified randomized groups remain similar to those of intent-to-treat groups (Figure
12B).
Instantaneous risk of cardiovascular death was highest immediately after the
procedure (Figure 13A), and hazard functions for non-cardiovascular death peaked
somewhat later (Figure 13B).
Competing risks of non-cardiovascular and uncategorizable deaths after
transfemoral (TF) TAVR were similar to those in the intent-to-treat analysis, but the
pattern of cardiovascular deaths was somewhat different due to absence of deaths
before treatment, which were generally cardiovascular (Figure 14A). After transapical
(TA) TAVR, patterns of risk were similar to those of intent-to-treat patients (Figure
14B), as were those after surgical AVR (Figure 14C).
Figure 9. CONSORT-style diagram of patients who did not receive assigned
randomized treatment in PARTNER-A.
Key: AVR, surgical aortic valve replacement; TAVR, transcatheter aortic valve
replacement
Figure 10. Mortality after randomization and before procedure in PARTNER-A.
A. Instantaneous risk of death. Solid line is parametric hazard estimate enclosed
within a dashed 68% confidence band equivalent to ±1 standard error. Patients are
censored at time of surgical or transcatheter aortic valve replacement, withdrawal
from the trial, or last follow-up, if alive without valve replacement.
B. Survival. Each symbol represents a death and vertical bars 68% confidence limits
equivalent to ±1 standard error. Solid line enclosed within a dashed 68% confidence
band represents parametric survival estimates. Numbers beneath the horizontal axis
are number of patients remaining at risk.
Figure 11. Cumulative distribution of interval from randomization to implant, stratified
by treatment group in PARTNER-A. The lag time for transcatheter aortic valve
replacement (TAVR) procedures in PARTNER-B mirrors that for PARTNER-A. For
orientation, vertical axis represents percentiles. Thus, the median value is the interval
at which cumulative distribution reaches 50%.
Key: AVR, surgical aortic valve replacement; TA-TAVR, transapical transcatheter
aortic valve replacement; TF-TAVR, transfemoral transcatheter aortic valve
replacement.
Figure 12. All-cause mortality in as-treated groups in PARTNER-A.
A. Instantaneous risk of death after transcatheter aortic valve replacement (TAVR)
via transfemoral (TF, green) or transapical (TA, blue) access, or surgical aortic valve
replacement (AVR, red) in PARTNER-A. Solid lines enclosed within dashed 68%
confidence bands are parametric estimates of the hazard function.
B. Survival stratified by randomized groups of as-treated patients in PARTNER-A.
Format is as in Figure E10B.
Figure 13. Instantaneous risk of cardiovascular and non-cardiovascular death in astreated patients after transcatheter aortic valve replacement (TAVR) via transapical
(TA, blue) or transfemoral (TF, green) access versus surgical aortic valve
replacement (AVR, red) in PARTNER-A. Dashed lines enclosing the solid parametric
hazard estimates form 68% confidence bands.
A. Cardiovascular death.
B. Non-cardiovascular death.
Figure 14. Competing risks of cardiovascular, non-cardiovascular, and
uncategorizable death after transcatheter aortic valve replacement (TAVR) via
transfemoral (TF) or transapical (TA) access, or surgical aortic valve replacement
(AVR) in as-treated PARTNER-A patients. Each symbol represents a death and
vertical bars 68% confidence limits equivalent to ±1 standard error. Solid lines
enclosed within dashed 68% confidence bands represent parametric survival
estimates.
A. Competing modes of death after TF-TAVR in PARTNER-A on expanded vertical
axis scale.
B. Competing modes of death after TA-TAVR in PARTNER-A on expanded vertical
axis scale.
C. Competing modes of death after AVR in PARTNER-A on expanded vertical axis
scale.