Abbott Absorb GT1 Bioresorbable Vascular Scaffold System Manual page 7

8.4.2 Summary of Clinical Results out to 1 year (Interim Data Cutoff)
Of the total of 605 patients registered in ABSORB EXTEND as of December 3, 2012, 37-day
(30 days ±7-day window), 194-day (180 days ±14-day window) and 393-day (365 days
±28-day window) clinical follow-up data were available for 591, 537, and 450 subjects,
respectively (Table 6). The composite endpoints are presented using the protocol definitions
for MI. The component endpoints are based on non-hierarchical counts unless otherwise
noted.
Table 6: ABSORB EXTEND Subject Counts of Ischemia-driven Adverse Events through
393 Days (All Subjects Registered Population)
ABSORB EXTEND ABSORB EXTEND
Events 0 – 37 Days 0 – 194 Days
(N = 591) (N = 537)
Hierarchical MACE 2.4% (14/591) 3.0% (16/537)
Hierarchical TVF 2.4% (14/591) 3.4% (18/537)
Non-Hierarchical Counts
Cardiac Death 0.2% (1/591) 0.2% (1/537)
MI 2.4% (14/591) 2.8% (15/537)
QMI 0.7% (4/591) 0.6% (3/537)
NQMI 1.7% (10/591) 2.2% (12/537)
ID-TLR 0.3% (2/591) 0.6% (3/537)
ID-non-TL TVR 0.0% (0/591) 0.6% (3/537)
Scaffold Thrombosis 0 – 30 days 0 – 194 days
Definite 0.3% (2/591) 0.4% (2/536)
Probable 0.2% (1/591) 0.2% (1/536)
Definite / Probable 0.5% (3/591) 0.6% (3/536)
Note: Subjects are only counted once for each type of event in each time period.
Note: All table entries were calculated based on the data from data cut-off date of
December 3, 2012.
The 37-day MACE and TVF rates of 2.4% were driven by MI events (10 NQMI and 3 QMI
hierarchically) that were all related to the target vessel. There was one cardiac death per
ARC definition. The overall non-hierarchical MI rate at 37 days was 2.4% (14/591) (10 NQMI
and 4 QMI).
The MACE rate increased to 3.0% at 6 months, attributed mostly to the 15 hierarchical MI
and 1 cardiac death. The TVF rate at 6 months was 3.4% (18/537 [1 cardiac death, 15 MI,
and 2 ID-Non-TL TVR hierarchically]). One patient who died at day 108 was adjudicated
as cardiac death per the ARC definition for cardiac death (0.2% at 194 days, 1/537). No
Absorb BVS was implanted in the target lesion in this patient because there was difficulty
in crossing the lesion with Absorb BVS. A metallic everolimus-eluting stent was implanted
instead. Over the same period, the ID-TLR rate was 0.6% (3/537) due to the occurrence of
two ID-TLR events by PCI and one ID-TLR event by CABG. The ID-non-TL TVR rate was 0.6%
(3/537) due to the occurrence of two ID-non-TL TVR events by CABG and one ID-non-TL
TVR event by PCI.
At 1 year, the MACE rate was 4.2% (19/450 [1 cardiac death, 13 MI (per protocol), and
5 ID-TLR hierarchically]). The TVF rate was 4.7% (21/450 [1 cardiac death, 13 MI (per
protocol), 5 ID-TLR, and 2 ID-non-TL TVR hierarchically]). The overall non-hierarchical MI
rate (per protocol) at 393 days was 2.9% (13/450) (9 NQMI and 4 QMI).
8.4.3 Summary of Clinical Results out to 2 years (Interim Data Cutoff)
In the subset of first 250 patients that reached 2-year follow-up (758 days) (19 July 2013
data cut), there was one case of cardiac death and the 758-day MACE and rate was low
(7.3%). TLF and TVF rates were also low at 6.9% and 8.1%, respectively. Further, the ARC
defined definite + probable scaffold thrombosis rate through 758-days for this population
was 0.8%.
Table 7: ABSORB EXTEND Subject Counts of Ischemia-driven Adverse Events through
758 Days (250 Subjects Registered Population)
30 Days, 6 Months,
Events N = 250 N = 250 N = 250
(30 ± 7 days) (180 ± 14 days) (365 ± 28 days)
Hierarchical,
Per protocol
MACE 2.0% (5/250) 2.8% (7/250) 4.4% (11/250)
TVF 2.0% (5/250) 3.2% (8/250) 4.8% (12/250)
TLF 2.0% (5/250) 2.8% (7/250) 4.4% (11/250)
Non-
hierarchical
counts
MI (per
2.0% (5/250) 2.4% (6/250) 2.8% (7/250)
protocol)
Cardiac
0.0% (0/250) 0.4% (1/250) 0.4% (1/250)
death
Ischemia-
driven 0.4% (1/250) 0.4% (1/250) 2.0% (5/250)
TLR
Ischemia-
driven non- 0.0% (0/250) 0.4% (1/250) 0.8% (2/250)
TL TVR
Scaffold
Thrombosis
0.4% (1/250) 0.4% (1/249) 0.8% (2/249)
(ARC Def /
Prob)
1. Data are % (number of subjects with event / number of subjects)
2. TLR = target lesion revascularization, TV = target vessel
3. MACE = major adverse cardiac events (composite endpoint of cardiac death, MI,
ischemia-driven TLR)
4. TLF = target lesion failure (composite endpoint of cardiac death, TVMI, ischemia-
driven TVR)
5. TVF = target vessel failure (composite endpoint of cardiac death, MI, ischemia-driven
TLR, ischemia-driven Non-TLR TVR)
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Conclusion: The interim outcomes from ABSORB EXTEND further demonstrate the 12- and
24-month safety and performance of Absorb BVS in a larger population of subjects where
longer lesion can be treated. Patients will be followed for up to 3 years.
8.5 Propensity Score Adjusted Analysis of Absorb BVS System and XIENCE V
Rationale and Method: Abbott Vascular is using its large body of historical clinical data on
XIENCE V stents as a control group for comparison against the currently available Absorb
BVS clinical data utilizing the propensity score method. Propensity score analysis is a
valid statistical method that is well accepted and commonly used in the clinical trial, and
in scientific and statistical communities for the comparison of data from non-randomized
studies. This approach adjusts for the baseline imbalance between the test and control
ABSORB EXTEND
groups, creates a better match between both groups, and hence, reduces real and potential
0 – 393 Days
bias in the comparative analysis. After propensity score adjustment, baseline characteristics
(N = 450)
between the two groups are more balanced, and therefore, the comparisons of the clinical
outcomes become more reliable. Key results for a 6-month and a 1-year propensity analysis
4.2% (19/450)
comparing Absorb BVS to XIENCE V data are presented using the inverse propensity score
4.7% (21/450) weighted (IPSW) method
additional data from ongoing trials become available. The results of this comparison are
being confirmed through ongoing clinical trials.
0.2% (1/450)
8.5.1 6-month Propensity Analysis
2.9% (13/450)
Thirty-eight patients from ABSORB Cohort B Group 1 and 73 XIENCE V patients treated with
3.0 x 18 mm stents from SPIRIT FIRST and SPIRIT II with 6-month QCA data are used for
0.9% (4/450)
this 6-month analysis. Their unadjusted 6-month MACE rates are 2.63% (1/38) and 4.11%
2.0% (9/450) (3/73), respectively.
Results: The propensity score adjustment yielded adjusted sample sizes of 34 (Absorb BVS)
1.8% (8/450)
and 66 (XIENCE V) from the 38 and 73, respectively, in the unadjusted arms. The adjusted
0.9% (4/450)
data were more balanced in baseline patient demographics and angiographic characteristics
between both arms. At 6 months, their clinical outcomes and angiographic results were
0 – 393 days
comparable. The adjusted 6-month MACE rates were 2.01% (0.7/34) and 5.27% (3.5/66),
0.7% (3/449) respectively, for the Absorb BVS and XIENCE V arms (Table 8) with a lower MACE observed
with Absorb BVS, a trend that is consistent with the results from the unadjusted groups.
0.2% (1/449)
Table 8: MACE at 6 Months from the IPSW-Adjusted Data
0.9% (4/449)
Clinical Outcomes at
6 Months
MACE
[95% CI]
The 6-month in-device late loss in the IPSW-adjusted arms was 0.14 ±0.18 mm for the
Absorb BVS System vs. 0.12 ±0.26 mm for the XIENCE V EECSS, representing a non-
significant difference in outcomes between the Absorb BVS System and the XIENCE V EECSS
(p = 0.68). Similarly, differences in the in-device % diameter stenosis, in-segment late loss,
and in-segment % diameter stenosis were not significant between the two devices in this
propensity score adjusted analysis (Table 9).
Table 9: Angiographic Outcomes at 6 Months from the IPSW-Adjusted Data
QCA Results at 6 Months
In-device % Diameter
Stenosis
In-segment % Diameter
Stenosis
In-device Late Loss (mm)
In-segment Late Loss (mm)
8.5.2 1-year Propensity Analysis
Prior to propensity adjustment, a total of 314 Absorb BVS pooled from Cohort B and an
interim dataset from ABSORB EXTEND, and 905 XIENCE V patients pooled from SPIRIT
FIRST, SPIRIT II, and SPIRIT III with 1-year follow-up were available, irrespective of the device
sizes used for their treatment. Their unadjusted 1-year MACE rates are 5.41% (17/314) and
5.64% (51/905), respectively.
1 year, 2 years,
Results: After the propensity adjustment, 282 Absorb BVS and 583 XIENCE V patients
N = 250
remained for the comparative analysis. An improved balance was achieved between both
(730 ± 28 days)
cohorts with the most striking changes observed in the lesion characteristics, which were
no longer statistically different between Absorb BVS and XIENCE V cohorts. The MI, ID-TLR,
MACE, and TLF (Target Lesion Failure defined as cardiac death, target vessel related MI and
ID-TLR) rates were comparable between both adjusted cohorts at 37, 193, and 393 days.
7.3% (18/248)
A summary of key 1-year outcomes is shown in Table 10. After adjustment, the MACE
rates remained comparable, with a numerically lower rate obtained for Absorb BVS (4.15%,
8.1% (20/248)
11.7/282) versus XIENCE V (5.63%, 32.8/583). The respective scaffold / stent thrombosis
6.9% (17/248)
rates were not statistically different (0.40% vs. 0.52%, p = 0.80).
Table 10: Clinical Outcomes at 1 year from the IPSW-Adjusted Cohorts
Clinical Outcomes
at 1 year
4.0% (10/248)
MACE
[95% CI]
0.4% (1/248)
MI
[95% CI]
4.0% (10/248)
ID-TLR
[95% CI]
TLF
[95% CI]
2.0% (5/248)
Definite / Probable
Scaffold / Stent
Thrombosis
0.8% (2/246)
[95% CI]
Discussion: The propensity score adjusted method achieved the intent of balancing the
baseline characteristics between both XIENCE V and Absorb BVS groups from different
ABSORB and SPIRIT trials. The adjusted results showed that Absorb BVS is comparable to
the XIENCE V stent for in-stent late loss at 6 months and for clinical outcomes at 6 months
and 1 year after implantation, and further confirms the comparability between Absorb BVS
and XIENCE V in the above parameters found in the unadjusted data.
Rosenbaum PR. Model-based direct adjustment. J Am Stat Assoc. 1987;82:387–394.
2
. Propensity analysis at later time points will be conducted as
12
Absorb BVS System XIENCE V
p-value
(N = 34) (N = 66)
2.01% (0.7) 5.27% (3.5)
0.44
[0.00%, 6.73%] [0.00%, 10.66%]
Absorb BVS System XIENCE V
p-value
(N = 34) (N = 66)
17.59 ±8.61 15.27 ±9.50 0.24
23.87 ±9.48 23.83 ±12.23 0.99
0.14 ±0.18 0.12 ±0.26 0.68
0.11 ±0.29 0.08 ±0.28 0.72
Absorb BVS XIENCE V
p-value
(N = 282) (N = 583)
4.15% 5.63%
0.35
[1.82%, 6.47%] [3.76%, 7.50%]
2.64% 2.52%
0.92
[0.77%, 4.51%] [1.25%, 3.80%]
1.95% 3.10%
0.33
[0.33%, 3.56%] [1.70%, 4.51%]
4.15% 5.09%
0.54
[1.82%, 6.47%] [3.30%, 6.87%]
0.40% 0.52%
0.80
[0.0%, 1.14%] [0.0%, 1.11%]
Printed on : 04/29/2015
8.5.3 2-year Propensity Analysis
As of the data cut-off on 19 July 2013, prior to propensity score matched analysis, a total
of 250 Absorb BVS and 887 XIENCE V patients were available through 2 years. Following
matching, 178 Absorb BVS and 293 XIENCE V patients remained for the comparative
analysis.
Results: After propensity score matched adjustment, 2-year MACE and TLF rates remained
similar between the Absorb BVS cohort and the XIENCE V cohort (6.7% vs. 8.9% for MACE,
and 6.2% vs. 8.2% for TLF, respectively). The Absorb BVS cohort exhibited a trend of lower
ID-TLR and cardiac death rate as compared to the XIENCE V cohort, although the differences
were not significant. The 2-year TVF rate was also numerically lower in the Absorb BVS
group (7.3% vs. 12.3%, p = 0.09). The adjusted definite / probable scaffold / stent
thrombosis rates were similar between Absorb BVS and XIENCE V at 2 years (0.6%; 95% CI
[0.01%, 3.09%] vs. 1.4%; 95% CI [0.37%, 3.46%], p=0.65). A summary of the key data is
shown below in Table 11.
Table 11: Clinical Outcomes at 2 years from the IPSW-Adjusted Cohorts
Clinical Outcomes Absorb BVS XIENCE V
at 2 years (N = 178) (N = 293)
Cardiac Death
0.0%
[0.00%, 2.05%] [0.37%, 3.46%]
[95% CI]
MI 4.5%
[95% CI] [1.96%, 8.66%] [2.38%, 7.47%]
ID-TLR
3.4%
[1.25%, 7.19%] [1.89%, 6.62%]
[95% CI]
TLF 6.2%
[95% CI] [3.12%, 10.79%] [5.32%, 11.94%]
MACE 6.7%
[95% CI] [3.53%, 11.48%] [5.88%, 12.73%]
TVF
7.3%
[95% CI] [3.95%, 12.17%] [8.76%, 16.60%]
Definite / Probable
Scaffold / Stent 0.6%
Thrombosis [0.01%, 3.09%] [0.37%, 3.46%]
[95% CI]
Note: Components (cardiac death, MI and ID-TLR) are presented as non-hierarchical.
Discussion: The comparability of Absorb BVS to XIENCE V demonstrated with in-scaffold /
stent late loss at 6 months (Cohort B only), and clinical outcomes at 6 months, and 1 year
were maintained through 2-years post implantation. The collective data confirms the
comparability between Absorb BVS and XIENCE V based on propensity analyses.
8.6 ABSORB II RCT
8.6.1 Study Design
The ABSORB II trial is a post-approval, randomized (Absorb BVS vs. XIENCE, 2:1), actively
controlled, single-blind, multicenter trial conducted in Europe and New Zealand. Patients can
be treated with a maximum of two de novo native coronary artery lesions. Scaffold sizes
were selected based on proximal and distal Dmax (maximum diameter) by on-line QCA ≥
2.25 mm to ≤ 3.8 mm and lesion lengths ≤ 48 mm. The study sizes include 2.5 x 18 mm,
2.5 x 28 mm, 3.0 x 18 mm, 3.0 x 28 mm, 3.5 x 12 mm, 3.5 x 18 mm, and 3.5 x 28 mm.
The co-primary endpoints are 1) vasomotion assessed by change in mean lumen diameter
between pre- and post-nitrate at 3 years (superiority), and 2) minimum lumen diameter
at 3 years post-nitrate minus minimum lumen diameter post-procedure post-nitrate (non-
inferiority, reflex to superiority). Patients will be clinically followed at 30 days, 180 days, and
at 1, 2, and 3 years post-procedure. The morphological as well as functional response will
be evaluated at 3 years based on imaging which will include angiography, IVUS / IVUS-virtual
histology, and Lipiscan, with MSCT evaluation at 3 years.
8.6.2 Summary of Clinical Outcome Data
The ABSORB II RCT trial completed its enrolment on June 4, 2013 with a total of 501
patients: Absorb BVS (N = 335); XIENCE (N = 166). One-year follow up data are
summarized in this section.
As shown in Table 12, the overall safety and performance of the Absorb BVS were similar to
the XIENCE. The 1-year TLF and MACE rates were comparable between the two device arms:
4.8% vs. 3.0% for TLF (p = 0.3473); and 5.2% vs. 3.0% for MACE (p = 0.2832). Both
Absorb BVS and XIENCE arms had no cardiac death, and low rates of MI, revascularizations,
and stent thrombosis. These adverse cardiovascular event rates were generally comparable
between the two treatment arms except for MI, which was trending higher in the Absorb
BVS arm (4.5% vs. 1.2%, p = 0.0549) and for all revascularization, which was trending
lower in the Absorb BVS arm (3.6% vs. 7.3%, p = 0.0758). The ARC definite stent / scaffold
thrombosis rates were similar between BVS (0.6%) and XIENCE (0.0%) (p = 1.000).
Table 12: Clinical Outcome through 1 year
Absorb BVS XIENCE
(N = 335) (N = 166)
Safety (Non-Hierarchical)
Death % 0.0% 0.6%
Cardiac death % 0.0% 0.0%
All MI 4.5% 1.2%
QMI 0.6% 0.0%
NQMI 3.9% 1.2%
Stent / Scaffold
0.6% 0.0%
thrombosis (ARC definite)
Effectiveness (Non-Hierarchical)
ID-TLR 1.2% 1.8%
ID-TVR, nonTLR 0.9% 1.8%
p-value
1.4%
0.30
4.4%
1.00
3.8%
1.00
8.2%
0.47
8.9%
0.49
12.3%
0.09
1.4%
0.65
Difference
p-value
(95% CI)
-0.61%
0.33
[-3.35%, 0.65%]
0.00%
1.00
[NA]
3.33%
0.055
[-0.24%, 6.29%]
0.61%
0.55
[-1.71%, 2.18%]
2.73%
0.095
[-0.77%, 5.55%]
0.6%
1.00
[11.7%, 2.16%]
-0.61%
0.69
[-4.08%, 1.61%]
-0.91%
0.41
[-4.35%, 1.19%]