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