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BVS: From Clinical Evidence to Daily Practice
Stephen G. Ellis, MD
Professor of Medicine
Senior Academic Officer
Director, Invasive/Interventional Cardiology
Cleveland Clinic Lerner College of Medicine
• Significant Consulting Fees
• Significant Consulting Fees
• Significant Consulting Fees
• Direct Research Support
• Direct Research Support
• Boston Scientific
• Abbott Vascular
• Medtronic
• Abbott Vascular
• Boston Scientific
Affiliation/Financial Relationship Company
Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a financial
interest/arrangement or affiliation with the organization(s) listed below.
Co-Principal Investigator, ABSORB III and IV
Best LTFU after DES: SORT Out II
SGE; 0317-4, 3
Galløe et al., JACC 2017;69:616-24
SORT OUT II- TLR
SGE; 0517-1, 3 Galløe, J. et al., J Am Coll Cardiol. 2017;69(6):616-24
MeRes (Meril Life Sciences)
Stanza (480 Biomedical)
Xinsorb (Huaan
Biotechnology)
Amaranth (Amaranth Medical)
ART18Z (ART 2nd generation)
ART (Arterial
Remodeling Technology)
IDEAL (BTI 2nd generation)
BTI (Xenogenics Corp.)
DESolve (Elixir Medical)
Absorb BVS (BVS 1.1)
BVS 1.0 (Abbott Vascular)
REVA (REVA Medical)
ReZolve (REVA 2nd
generation)
AMS 4.0 (Dreams 2nd generation)
AMS 3.0 (Dreams 1st generation)
AMS 1.0 (Biotronik)
Igaki-Tamai (Kyoto Medical)
BRS (Micropost)
Everolimus/PDLLA (1:1) matrix coating
• 7 µm
• Conformal coating
• Controlled drug release similar to Xience CoCr-EES
PLLA Backbone
• Semi-crystalline
• Circumferential sinusoidal rings connected by linear links
• Strut thickness 150 µm
• Platinum markers in each end ring
Fully
Bioresorbable
Absorb BVS
Early BVS Thrombogenicity
• Ex vivo AV shunt in pigs (carotid artery-JV)
• 3 stents deployed in a series in a silicone tube
• Order of devices was varied in different shunts
• Stents exposed to flowing blood for ~60 minutes
• Staining for platelets (CD61) was performed
Absorbable Polymer DES vs. BVS
Koskinas et al. JACC 2012;59:1337-49 SGE; 0814-7, 7
\\\\
Any early excess risk will be offset
by long term benefit
The BVS Value Proposition
Absorb Beyond 2 Years: Cohort B. vs Xience 5-Year FU (3.0 x 18 mm)
Days 0 37 194 284 393 573 758 1123 1488 1853
Absorb 101 99 96 96 94 92 91 88 86 85
Xience 227 224 219 211 204 202 191 182 174 169
Serruys PW. TCT 2015 SGE; 0317-3, 13
ABSORB II: In-segment Late Lumen Loss at 3 Years
3 Years Excluding Def. ST
BVS 0.29 ± 0.54mm (238) 0.24 ± 0.43mm (232)
CoCr-EES 0.16 ± 0.40 mm
(119)
0.16 ± 0.40 mm (119)
P-value (t-test) 0.007 0.06
Definite Late ST on Day 139
Definite VLST (Day 494-810)
SGE; 0617-3, 3
Risk Estimates of Device Thrombosis
SGE; 0617-8, 1
Montone., et al, Circulation 2017;135:2145-2154
LEARNING CURVE A BVS-specific implantation strategy can improve outcomes
P PREPARE THE LESION S SIZE APPROPRIATELY P POST-DILATE
Adapted from Gori, T., EuroPCR 2015 and Puricel S et al. JACC 2016;67:921–31
P
S
P (N=292)
(N=369)
3.3%
1.0%
Log rank p=0.02
0
100 200 300 400 0
Days
Early Experience
BVS-specific Protocol
1
2
3
4
5 Scaffold thrombosis (%) Propensity-matched groups
• Pooled ABSORB data at 2 years: ABSORB EXTEND,
ABSORB II, ABSORB Japan, ABSORB China, and
ABSORB III
• Definition of Full PSP (must satisfy all the criteria
below)
Pre-dilatation (performed in 99.9% of Absorb patients)
Sizing (vessel): 2.25mm ≤ QCA RVD ≤ 3.5mm
Post-dilatation:
• Pressure ≥ 18 atm
• Balloon diameter: Scaffold diameter > 1:1 and Balloon diameter
≤ Scaffold diameter + 0.5mm
PSP Analysis
PSP Analysis
Pooled ABSORB Trials Absorb Arm1
Implantation Technique
Absorb
(N=2858)
Pre-dilatation 99.9%
2.25 mm ≤ QCA RVD ≤ 3.5 MM 79.3%
High pressure Post-dilatation2 12.8%
Full PSP3 10.4%
1. Based on patient population treated with Absorb BVS in ABSORB II, ABSORB III, ABSORB
China, ABSORB Japan and ABSORB EXTEND
2. Defined as post-dilatation balloon pressure ≥18 atm, post-dilatation balloon diameter > nominal
scaffold diameter and post-dilatation balloon diameter ≤nominal scaffold diameter+0.5mm
3. Defined as patients with pre-dilatation, QCA RVD ≥2.25mm-≤3.5mm, and high pressure post-
dilatation defined above in 2
12,1
2,6
8,9
1,9
9,0
1,9
7,6
1,5
6,7
0,9
5,5
0,7
0
2
4
6
8
10
12
14
16
18
20
TLF ST (Def/Prob) TLF ST (Def/Prob) TLF ST (Def/Prob)
1. Based on patient population treated with Absorb BVS in ABSORB II, ABSORB III, ABSORB China, ABSORB Japan and ABSORB EXTEND
2. Defined as post-dilatation balloon pressure ≥18 atm, post-dilatation balloon diameter > nominal scaffold diameter and
post-dilatation balloon diameter ≤nominal scaffold diameter+0.5mm
3. Defined as patients with pre-dilatation, QCA RVD ≥2.25mm-≤3.5mm, and high pressure post-dilatation defined above in 2.
QCA RVD ≥ 2.25 mm
to ≤ 3.5 mm
High Pressure
Post-dilatation2
Even
ts (
%)
fro
m 1
to
2 Y
ears
Impact of Implantation Technique on Clinical Outcomes
from 0 to 2 Years – Pooled Trials Absorb Arm1
P=0.0006 P=0.047
Full PSP3
No (N=590) Yes (N=2261) No (N=2493) Yes (N=365) No (N=2559) Yes (N=298)
Literature and Industry Review for:
High quality RCT or registries with ≥ 200 BVS
patients, clinical follow up ≥12 months, clinical
and QCA data potentially available
105 cases;
210 controls
ABSORB II, China and Japan
report VLST; PSP defined
Extended study through
3 year follow up as possible
177 cases (55 VLST); 354 controls
through 24-48 months
N = 18
N = 14 studies
Statistical Analysis
Plan Developed
• 10 cases: covariate
• Covariates prioritized
• 2:1 control cases
• 12 month ST primary
endpoint (30 day ST and
1-12 months ST identified
as secondary endpoints)
• Dedicated CRF with
definitions
Separate 12-48 month
study of VLST using same
criteria
Addition of PSP as
covariate
4 Declined
SGE; 0317-1, 3
Multicenter BVS Consortium
Independent Correlates of
0-12 Month Scaffold Thrombosis
Odds Ratio p
Model 1
Off DAPT 3.47 0.006
No Post Dilatation ≥1.1 2.29 0.022
RVD <2.40 2.12 0.036
Model p=0.002 McFadden’s Rho-sq=0.052 c-statistic-=0.64
Model 2
MLD<1.85 mm 3.07 0.004
Off DAPT 2.49 0.053
Model p=0.003 McFadden’s Rho-sq=0.051 c-statistic-=0.63
SGE; 0317-1, 20
Independent Correlates of
12-48 Month Scaffold Thrombosis
Univ OR Univ p Multi OR Multi p
Scaffold:RVD <1.18 7.5 0.002 4.7 0.029
RVD > 2.72 mm 3.4 0.001 2.2 0.086
SGE; 0317-1, 20
No apparent effect of post-dilatation parameters, DAPT
• The Absorb scaffold’s ultimate role will depend
on whether or not it meets long term
expectations
• For now, it seems reasonable for use in
patients with stable CAD, 2.4<RVD<3.0, with
meticulous attention to implant technique
• Use of 2nd Gen DAPT is not unreasonable for at
least 30 days, especially in patients at higher
risk of scaffold thrombosis
Summary and Overall Conclusions
\\\\
Any early excess risk will be offset
by long term benefit
The BRS Value Proposition
\\\\
Any early excess risk will be offset
by long term benefit
The BRS Value Proposition
Seems Reasonable, but
\\\\
Any early excess risk will be offset
by long term benefit
The BRS Value Proposition
Lots of Ongoing Work- Yet
Remains Unproven