1. One-Year Patient-Level Pooled Meta-analysis From 4 ABSORB Trials in 3389 Randomized Patients
Gregg W. Stone, MD
Columbia University Medical Center
NewYork-Presbyterian Hospital
Cardiovascular Research Foundation

2. Disclosures Consultant to Reva
Study chairman for ABSORB III and IV (uncompensated)

3. ABSORB 1-Year Meta-analysis Objectives and endpoints
Objective: To evaluate the 1-year relative outcomes of the ABSORB BVS compared to the Xience CoCr-EES for the treatment of simple and moderately complex lesions in pts with stable CAD and stabilized ACS
Primary endpoints:
The patient-oriented composite endpoint (PoCE) of death, all MI or all revascularization
The device oriented composite endpoint (DoCE) of cardiac death, TV-MI or ID-TLR (=TLF)
Secondary endpoints:
Safety: Death, MI, and device thrombosis
Efficacy: Revascularization, ID-TVR, ID-TLR

4. ABSORB 1-Year Meta-analysis
Methodology
Studies: All RCTs of Absorb vs. Xience in stable CAD or stabilized ACS with ≥1-year clinical follow-up
Treatment effects were evaluated by:
Mantel–Haenszel fixed effect model (preferred to a random effect model when few events (<5) are present in any of the treatment arms, and provides similar results as an inverse variance weighted model for non-zero events); Heterogeneity between trials was evaluated with Cochran’s Q test and the I2 statistic
Patient-level pooled time to event analysis; univariable outcomes compared with Wald 2 test, adjusted by study
Multivariable logistic regression using backward selection, adjusted by study

5. *Maximum 1 lesion per vessel
4 ABSORB RCTs, 3389 patients
ABSORB II
ABSORB Japan
ABSORB China
ABSORB III
ClinicalTrials.gov
NCT
NCT
NCT
NCT
N centers 46 38 24
193
N randomized pts
501
400
480
2,008
- assigned to BVS
335
266
241
1,322
- assigned to CoCr-EES
166
134
239
686
N study lesions
1 or 2
N study vessels*
*Maximum 1 lesion per vessel

6. 4 ABSORB RCTs, 3389 patients ABSORB II ABSORB Japan ABSORB China
ABSORB III
Target lesion RVD (mm)
Max LD to 3.8 by online QCA
≥2.5 to ≤3.75
Target lesion length (mm)
≤48
≤24
Device overlap allowed
Yes
Bailout only
1-year clinical follow-up
98.4%
99.3%
99.0%
99.1%
Routine angiographic FU
At 3 years
At 13 months
At 12 months No
Primary endpoint
Angio vasomotion at 3 years
TLF at 1 year
Angio in- segment late loss at 1 year
TLF at 1 year
Total follow-up
5 years

7. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Baseline features
BVS (N=2164)
CoCr-EES (N=1225)
P value
Age (years)
62.9 ± 10.8
62.5 ± 10.4
0.25
Male
72.6%
72.3%
0.86
BMI (kg/m2)
28.8 ± 5.9
28.5 ± 5.7
0.17
Diabetes mellitus
30.2%
30.0%
0.91
- Insulin-treated
9.6%
9.8%
0.83
Hypertension
75.1%
73.8%
0.40
Hyperlipidemia
71.3%
69.3%
0.22
Current smoking
22.7%
23.8%
0.48
Prior PCI
33.1%
30.5%
0.11
Prior CABG
3.2%
2.5%
0.28
Prior MI
21.3%
22.0%
0.65
Renal insufficiency*
9.3%
8.2%
0.37
*Estimated glomerular filtration rate <30 ml/min/1.73m² or dialysis

8. ABSORB 1-Year Meta-analysis Presenting symptoms and antiplatelet meds
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Presenting symptoms and antiplatelet meds
BVS (N=2164)
CoCr-EES (N=1225)
P value
Pre-PCI evidence of ischemia
- Silent ischemia
11.7%
10.3%
0.21
- Stable angina
55.3%
53.3%
0.27
- Unstable angina
27.9%
31.0%
0.06
- Recent MI
3.1%
4.0%
0.14
- Post-MI angina
0.7%
0.77
- None
1.3%
0.13
Index procedure loading dose
- Aspirin*
97.5%
96.7%
0.16
- P2Y12 receptor inhibitor
98.5%
98.0%
0.22
- Clopidogrel or ticlopidine
75.9%
78.9%
0.047
- Prasugrel or ticagrelor
24.1%
21.1%

9. ABSORB 1-Year Meta-analysis Baseline angiographic features
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Baseline angiographic features
BVS
(N=2164)
(L=2275)
CoCr-EES
(N=1225)
(L=1284)
P value
Number of lesions treated (any)*
1.1 ± 0.4
1.2 ± 0.4
0.69
Number of target lesions treated
1.1 ± 0.2
1.0 ± 0.2
0.72
- One
94.5%
94.9%
0.66
- Two
5.3%
5.0%
0.67
Target coronary artery (lesion level)
- Left main
0.0%
1.0
- Left anterior descending
46.0%
44.8%
0.49
- Left circumflex
25.5%
27.8%
0.14
- Right
28.4%
27.4%
0.51
*Randomized target lesions plus non-randomized non-target lesions in a separate epicardial coronary artery

10. ABSORB 1-Year Meta-analysis Baseline angiographic features
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Baseline angiographic features
BVS
(N=2164)
(L=2275)
CoCr-EES
(N=1225)
(L=1284)
P value
Lesion characteristics (lesion level)
- Calcification (moderate or severe)
27.5%
26.5%
0.55
- Tortuosity (moderate or severe)
4.5%
4.6%
0.91
- Eccentric
80.4%
79.7%
0.59
- Bifurcation*
33.1%
35.2%
0.20
- Thrombus
0.4%
0.3%
1.0
- ACC/AHA class B2/C
66.6%
69.5%
0.07
Quantitative measures (lesion level)
- RVD, mm
2.68 ± 0.44
2.69 ± 0.46
0.27
- MLD, mm
0.96 ± 0.37
0.95 ± 0.36
0.58
- DS, %
64.1 ± 12.4
64.6 ± 12.0
0.26
- Lesion length, mm
13.1 ± 5.6
13.4 ± 5.7
0.09
*Defined by the angio core lab as having a side branch with diameter ≥1.5 mm. The protocol of each study excluded bifurcation lesions with a side branch diameter ≥2.0 mm by visual estimate.

11. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Procedural and angiographic results (core lab)
BVS
(N=2164)
(L=2275)
CoCr-EES
(N=1225)
(L=1284)
P value
Number of study devices per patient
1.1 ± 0.4
0.98
Total device length per lesion, mm
18.8 ± 6.9
19.6 ± 7.1
0.0008
Overlapping study devices per lesion
7.0%
7.4%
0.65
Maximum device diameter per lesion, mm*
3.17 ± 0.41
3.16 ± 0.43
0.36
Maximum device pressure per lesion, atm*
15.5 ± 3.2
15.7 ± 3.3
0.28
Post-dilatation performed (per lesion)
66.2%
55.3%
<0.0001
Bail-out device used (per lesion)
4.4%
5.6%
0.12
IVUS or OCT guidance (per procedure)
23.9%
20.3%
0.02
Procedure duration, minutes
43.7 ± 23.7
39.7 ± 21.5
*Device delivery system or post-dilatation balloon

12. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Procedural and angiographic results (core lab)
BVS
(N=2164)
(L=2275)
CoCr-EES
(N=1225)
(L=1284)
P value
Post-PCI (lesion level)
- RVD, mm
2.71 ± 0.44
2.75 ± 0.45
0.02
- In-device
- Acute gain, mm
1.41 ± 0.45
1.58 ± 0.43
<0.0001
- MLD, mm
2.37 ± 0.39
2.53 ± 0.40
- DS, %
12.4 ± 8.3
7.5 ± 8.2
- In-segment
1.20 ± 0.45
1.24 ± 0.45
0.04
2.16 ± 0.40
2.19 ± 0.43
0.07
19.9 ± 7.7
19.9 ± 8.4
0.96
Device success (per lesion)*
95.6%
99.4%
Procedure success (per patient)**
94.9%
97.0%
0.003
*Device success: Successful deployment of study scaffold/stent at intended target lesion with final QCA DS <30%
**Procedure success: Device success (any device) without cardiac death, TV-MI or TLR during hospital stay (max 7 days)

13. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Dual anti-platelet therapy use during follow-up
BVS
(N=2164)
CoCr-EES
(N=1225)
P-value
30-day medication use
P2Y12 receptor antagonist
100.0%
99.8%
0.14
Clopidogrel or ticlopidine
78.7%
82.4%
0.01
Prasugrel or ticagrelor
21.3%
17.3%
0.006
Aspirin
99.5%
0.92
DAPT
99.3%
0.41
1-year medication use
95.4%
95.6%
0.78
76.6%
80.8%
0.005
18.8%
14.8%
0.004
Any, duration (days)
356 ± 44
356 ± 43
0.94
98.3%
97.5%
0.09
Duration (days)
356 ± 46
355 ± 48
0.48
94.0%
93.8%
0.81
352 ± 52
351 ± 55

14. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
1-Year PoCE: Mortality, MI, or Revascularization
Absorb
BVS
XIENCE
CoCr-EES
Study
Absorb II
Absorb China
Absorb Japan
Absorb III
Summary
27/331
19/238
26/265
184/1313
256/2147
17/165
23/237
11/133
78/677
129/1212
RR [95% CI]
0.76 [0.43, 1.36]
0.82 [0.46, 1.47]
1.19 [0.60, 2.33]
1.22 [0.95, 1.56]
1.09 [0.89, 1.34]
RR [95% CI]
Fixed: MH
Random: DL
Test for overall effect: Z=0.88; P=0.38
0.1
0.5
1.0
5.0
10.0
Test for heterogeneity: I2=5.1%; P=0.37
Absorb
BVS Better
Xience CoCr-EES
Better
PoCE = Patient-oriented composite endpoint

15. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
PoCE: Death, MI or Revascularization (pooled)
20%
Absorb BVS (n=2161)
XIENCE CoCr-EES (n=1223)
15%
Difference [95%CI] = 1.0% [-1.1%, 3.1%]
HR [95%CI] = 1.12 [0.89,1.40]
P=0.34
or revascularization (%)
Death, MI,
10.3%
10%
9.3% 5% 0% 1 2 3 4 5 6 7 8 9 10 11 12
Months Post Index Procedure
Number at risk
Absorb BVS
XIENCE CoCr-EES
2161
1223
2056
1184
1994
1151
1960
1123
1919
1102
PoCE = Patient-oriented composite endpoint

16. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Independent baseline predictors of 1-year events
 PoCE (death, MI, or revascularization)
RR [95%CI]
P value
Diabetes present
1.39 [1.15, 1.68]
0.0008
Prior cardiac intervention
1.40 [1.16, 1.69]
0.0006
Number of target lesions (≥2 vs. 1)
1.45 [1.16, 1.82]
0.001
Any lesion with MLD < median (0.93 mm)*
1.37 [1.13, 1.68]
0.002
Any lesion with RVD < median (2.65 mm)*
1.23 [1.01, 1.51]
0.04
Any ACC/AHA class B2 or C lesion (vs. A or B1)*
1.38 [1.11, 1.73]
0.003
BVS (vs. CoCr-EES)
1.10 [0.90, 1.51]
0.29
*Angio core lab determination. The following variables were entered into the model: age (median 63 years), sex, current smoking, hypertension, hyperlipidemia, diabetes, prior MI, prior cardiac intervention, presentation with unstable angina/recent MI (vs. stable ischemic syndrome), # target lesions (≥2 vs. 1), loading with prasugrel or ticagrelor (vs. clopidogrel or ticlopidine), RVD (any lesion < median 2.65 mm), MLD (any lesion < median 0.93 mm), lesion length (any lesion < median mm), any ACC/AHA class B2/C lesion (vs. A/B1), any LAD lesion, any lesion with mod/severe calcification, and any bifurcation lesion. Device randomization was forced into the model.

17. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
1-Year DoCE (TLF): Cardiac Death, MI or ID-TLR
Absorb
BVS
XIENCE
CoCr-EES
Study
Absorb II
Absorb China
Absorb Japan
Absorb III
Summary
20/331
8/238
11/265
102/1313
141/2147
7/165
10/237
5/133
41/677
63/1212
RR [95% CI]
1.42 [0.61, 3.30]
0.80 [0.32, 1.98]
1.10 [0.39, 3.11]
1.28 [0.90, 1.82]
1.22 [0.91, 1.64]
RR [95% CI]
Fixed: MH
Random: DL
Test for overall effect: Z=1.36; P=0.18
0.1
0.5
1.0
5.0
10.0
Test for heterogeneity: I2=0%; P=0.78
Absorb
BVS Better
Xience CoCr-EES
Better
DoCE = Device-oriented composite endpoint

18. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
DoCE (TLF): Cardiac Death, MI or ID-TLR (pooled)
20%
Absorb BVS (n=2161)
XIENCE CoCr-EES (n=1223)
15%
Difference [95%CI] = 1.2% [-0.4%, 2.7%]
HR [95%CI] = 1.25 [0.92,1.70]
P=0.16
Target lesion failure (%)
10%
6.0% 5%
4.9% 0% 1 2 3 4 5 6 7 8 9 10 11 12
Months Post Index Procedure
Number at risk
Absorb BVS
XIENCE CoCr-EES
2161
1223
2065
1188
2037
1174
2022
1161
2003
1150
DoCE = Device-oriented composite endpoint

19. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Independent baseline predictors of 1-year events
DoCE (TLF: cardiac death, TV-MI, or ID-TLR)
RR [95%CI]
P value
Diabetes present
1.56 [1.19, 2.04]
0.002
Prior cardiac intervention
1.36 [1.03, 1.78]
0.03
Any lesion with MLD < median (0.93 mm)*
1.37 [1.03, 1.82]
Any lesion with RVD < median (2.65 mm)*
1.52 [1.14, 2.03]
0.005
Any ACC/AHA class B2 or C lesion (vs. A or B1)*
1.65 [1.19, 2.28]
BVS (vs. CoCr-EES)
1.23 [0.92, 1.64]
0.14
*Angio core lab determination. The following variables were entered into the model: age (median 63 years), sex, current smoking, hypertension, hyperlipidemia, diabetes, prior MI, prior cardiac intervention, presentation with unstable angina/recent MI (vs. stable ischemic syndrome), # target lesions (≥2 vs. 1), loading with prasugrel or ticagrelor (vs. clopidogrel or ticlopidine), RVD (any lesion < median 2.65 mm), MLD (any lesion < median 0.93 mm), lesion length (any lesion < median mm), any ACC/AHA class B2/C lesion (vs. A/B1), any LAD lesion, any lesion with mod/severe calcification, and any bifurcation lesion. Device randomization was forced into the model.

20. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
All-cause Mortality (pooled)
20%
Absorb BVS (n=2161)
XIENCE CoCr-EES (n=1223)
15%
All-cause mortality (%)
10%
Difference [95%CI] = 0.0% [-0.6%, 0.6%]
HR [95%CI] = 1.06 [0.46,2.40]
P=0.90 5%
0.8% 0%
0.7% 1 2 3 4 5 6 7 8 9 10 11 12
Months Post Index Procedure
Number at risk
Absorb BVS
XIENCE CoCr-EES
2161
1223
2146
1219
2138
1214
2132
1207
2124
1204

21. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Myocardial Infarction (pooled)
20%
Absorb BVS (n=2161)
XIENCE CoCr-EES (n=1223)
15%
Difference [95%CI] = 1.4% [-0.1%, 2.9%]
HR [95%CI] = 1.36 [0.97,1.90]
P=0.07
Myocardial infarction (%)
10%
5.5% 5%
4.1% 0% 1 2 3 4 5 6 7 8 9 10 11 12
Months Post Index Procedure
Number at risk
Absorb BVS
XIENCE CoCr-EES
2161
1223
2067
1188
2035
1175
2021
1163
2007
1158

22. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Device Thrombosis (Def/Prob) (pooled)
20%
Absorb BVS (n=2161)
XIENCE CoCr-EES (n=1223)
15%
Device thrombosis (%)
10%
Difference [95%CI] = 0.7% [0.0%, 1.3%]
HR [95%CI] = 2.11 [0.92,4.83]
P=0.08 5%
1.3%
0.6% 0% 1 2 3 4 5 6 7 8 9 10 11 12
Months Post Index Procedure
Number at risk
Absorb BVS
XIENCE CoCr-EES
2161
1223
2128
1213
2114
1207
2108
1200
2098
1197

23. ABSORB 1-Year Meta-analysis
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
ID-Target Lesion Revascularization (pooled)
20%
Absorb BVS (n=2161)
XIENCE CoCr-EES (n=1223)
15%
Ischemia-driven
TLR (%)
10%
Difference [95%CI] = 0.5% [-0.6%, 1.5%]
HR [95%CI] = 1.24 [0.76,2.04]
P=0.39 5%
2.4%
1.9% 0% 1 2 3 4 5 6 7 8 9 10 11 12
Months Post Index Procedure
Number at risk
Absorb BVS
XIENCE CoCr-EES
2161
1223
2125
1213
2106
1201
2092
1192
2074
1181

24. ABSORB 1-Year Meta-analysis Meta-analysis summary
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Meta-analysis summary
BVS
(N=2164)
CoCr-EES
(N=1225)
RR [95% CI]
Fixed effect
P Value I2
P het
Patient-oriented composite endpoint
(PoCE; mortality, MI or revascularization)
11.9%
10.6%
1.09 [0.89, 1.34]
0.38
5.1%
0.37
Device-oriented composite endpoint
(DoCE - TLF; cardiac death, TV-MI or ischemia-driven TLR)
6.6%
5.2%
1.22 [0.91, 1.64]
0.17 0%
0.78
het = heterogeneity

25. ABSORB 1-Year Meta-analysis Meta-analysis summary
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Meta-analysis summary
BVS
(N=2164)
CoCr-EES
(N=1225)
RR [95% CI]
Fixed effect
P Value I2
P het
All-cause mortality
0.8%
0.7%
1.12 [0.47, 2.69]
0.80 NA
- Cardiac
0.4%
0.3%
1.26 [0.33, 4.82]
0.74
- Non-cardiac
1.02 [0.32, 3.25]
0.97
All MI
5.7%
4.0%
1.34 [0.97, 1.85]
0.08 0%
0.71
- Peri-procedural (AIII def)
2.9%
2.2%
1.29 [0.82, 2.03]
0.27
0.75
- Peri-procedural (SCAI def)
0.97 [0.44, 2.14]
0.94
0.63
- Non-peri-procedural (AIII def)
2.8%
1.8%
1.48 [0.91, 2.40]
0.11
0.93
- TV-MI
5.1%
3.3%
1.45 [1.02, 2.07]
0.04
- Non-TV-MI
0.9%
0.75 [0.34, 1.66]
0.48
NA = not applicable - cannot test for heterogeneity because no events were present in one cell in 3 of the 4 trials; het = heterogeneity

26. ABSORB 1-Year Meta-analysis Meta-analysis summary
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Meta-analysis summary
BVS
(N=2164)
CoCr-EES
(N=1225)
RR [95% CI]
Fixed effect
P Value I2
P het
Device thrombosis (def/prob)
1.3%
0.6%
2.09 [0.92, 4.75]
0.08 0%
0.40
- Definite
1.1%
0.5%
2.06 [0.85, 5.03]
0.11
0.84
- Probable
0.2%
0.1%
2.28 [0.28, 18.51]
0.44 NA
- Early (0-30 days)
0.9%
1.76 [0.72, 4.34]
0.22
0.70
- Late (30 days - 1 year)
0.4%
4.10 [0.52, 32.56]
0.18
NA = not applicable - cannot test for heterogeneity because no events were present in one cell in 3 of the 4 trials; het = heterogeneity

27. ABSORB 1-Year Meta-analysis Meta-analysis summary
ABSORB II, ABSORB III, ABSORB Japan, ABSORB China
Meta-analysis summary
BVS
(N=2164)
CoCr-EES
(N=1225)
RR [95% CI]
Fixed effect
P Value I2
P het
All revascularization
7.9%
7.7%
1.02 [0.80, 1.30]
0.89
21.9%
0.28
ID-TVR
4.3%
3.7%
1.14 [0.80, 1.62]
0.47
11.2%
0.34
ID-TLR
2.7%
2.3%
1.14 [0.73, 1.79]
0.56 0%
0.91
het = heterogeneity

28. ABSORB 1-Year Meta-analysis
Conclusions from 4 trials and 3,389 randomized patents
For treatment of simple and moderately complex lesions in pts with stable CAD and stabilized ACS, the ABSORB BVS, compared to the Xience CoCr-EES, resulted in:
Similar rates of the patient-oriented and device- oriented composite endpoints, consistent with comparable overall outcomes at 1 year
Non-significantly different rates of major safety outcomes, including death, MI, and device thrombosis
No significant difference in peri-procedural MI, but a small increase in TV-MI
Comparable measures of efficacy, including ID-TLR, ID-TVR and all revascularization