Bioresorbable Coronary ScaffoldsBill D GogasHabib Samady

33

Textbook: Interventional Cardiology, 2nd Edition 2016

CE mark FDA, CE mark CE mark

CE mark

Strut coverage is delayed in segments treated with overlapping Absorb scaffolds

Strut coverage is comparable among segments treated with overlapping Absorb scaffolds and metallic stents

Lumen and vessel enlargement initiationScaffold’s strut core sites remain acellular

JACC Cardiovasc Interv. 2016 Apr 25;9(8):852-5

Restored vasomotor function of Absorb treated segmentsRestored pulsatility of Absorb treated segments

Scaffold’s strut core sites have “preserved box” appearance and polymer is being replaced by matrix

Gene levels of Cx43 are increased in Absorb treated arterial segments

Light intensity of strut core sites surges due to gradual cellularization by connective tissue

Late lumen enlargement

The Absorb BVS is completely degraded

Thinning of vessel wall attributed to late lumen enlargementRestored vasomotor function of Absorb treated segments

Resorption sites have >50% of collagen-rich connective tissue and are fully integrated in the vessel wall

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501 patients were randomly assigned to the Absorb group or the Xience group. At 3 year follow-up, the primary endpoint was superiority of the Absorb BVS vs. the XV stent in angiographic vasomotor reactivity after administration of intracoronary nitrate.

Absorb BVS n=258 0.047±0.109 mm

XIENCE n=130 0.056±0.117 mm

Vasomotion (mm)

Cum

ulat

ive

frequ

ency

Psuperiority= 0.49

Lancet. 2016 Nov 19;388(10059):2479-2491

J Am Coll Cardiol Intv 2016;9:728–41

- A total of 15 Absorb BVS (3.0x18.0-mm) and 14 XV (3.0x18.0-mm or 3.0x12.0-mm) stents were randomly implanted in the main coronaries of 12 non-atherosclerotic swine.

- Vasomotor performance (constrictive and expansive) was measured in the stented/scaffolded segments and the 5-mm proximal and distal adjacent segments at 1 year (n=6) and 2 years (n=6)

35.91 +/- 24.74% vs. 1.20 +/- 3.79% (p < 0.01)

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Absorb BVS Xience V

J Am Coll Cardiol Intv 2016;9:728–41

% Relaxation Assessed w/ Substance P (Endothelial Dependent Vasorelaxation)

35.91 +/- 24.74% vs. 1.20 +/- 3.79% (p < 0.01)

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Absorb BVS Xience V

J Am Coll Cardiol Intv 2016;9:728–41

% Relaxation Assessed w/ Substance P (Endothelial Dependent Vasorelaxation)

501 patients were randomly assigned to the Absorb group or the Xience group. At 3 year follow-up, the co-primary endpoint was the non-inferiority angiographic LLL.

Lancet. 2016 Nov 19;388(10059):2479-2491

Cum

ulat

ive

frequ

ency

Pnon-inferiority= 0.78

Absorb n=298 0.37±0.45 mmXIENCE n=151 0.25±0.25 mm

Late Luminal Loss: In-stent/ In-scaffold (mm)

8 definite scaffold thromboses (one acute, one subacute, six very late) and 1 late probable scaffold thrombosis in the Absorb BVS group (3%), and no definite or probable stent

thrombosis in the XV group (p=0.0331) over the course of 3 years

Lancet. 2016 Nov 19;388(10059):2479-2491

Angiographic, in-stent/scaffold assessment

Optimal Implantation Technique is Imperative for Good Clinical Outcomes:

“The PSP Rule for Absorb BVS Deployment”

1. Prepare the lesion to receive scaffold w/ NC balloon sized 1:1 2. Facilitate delivery 3. Enable full expansion of pre-dilatation balloon to facilitate full scaffold

expansion and improve vessel compliance

1. Accurately size the vessel (2.5-3.75 mm) w/ intracoronary imaging 2. Select appropriate scaffold for “best fit”

1. Mandatory post-dilatation w/ NC balloon2. Achieve <10% final residual stenosis 3. Ensure full strut apposition

1. Prepare the lesion to receive scaffold w/ NC balloon sized 1:1 2. Facilitate delivery 3. Enable full expansion of pre-dilatation balloon to facilitate full scaffold

expansion and improve vessel compliance

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ion

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Optimal Implantation Technique is Imperative for Good Clinical Outcomes:

“The PSP Rule for Absorb BVS Deployment”

Abs

orb

BVS

2.5

x12-

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dep

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1. Accurately size the vessel (2.5-3.75 mm) w/ intracoronary imaging 2. Select appropriate scaffold for “best fit”

Optimal Implantation Technique is Imperative for Good Clinical Outcomes:

“The PSP Rule for Absorb BVS Deployment”

1. Mandatory post-dilatation w/ NC balloon2. Achieve <10% final residual stenosis 3. Ensure full strut apposition

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Optimal Implantation Technique is Imperative for Good Clinical Outcomes:

“The PSP Rule for Absorb BVS Deployment”

8 definite scaffold thromboses (one acute, one subacute, six very late) and 1 late probable scaffold thrombosis in the Absorb BVS group (3%), and no definite or probable stent

thrombosis in the XV group (p=0.0331) over the course of 3 years

Lancet. 2016 Nov 19;388(10059):2479-2491

Angiographic, in-stent/scaffold assessment

ConclusionThe trial did not meet its co-primary endpoints of superior vasomotor reactivity

and non-inferior late luminal loss for the Absorb BVS with respect to the metallic stent, which was found to have significantly lower late luminal loss

than the Absorb BVS.

The PSP Rule for Absorb BVS Deployment in AB II was implemented in 6.5%

2008 patients with stable or unstable angina were randomly assigned in a 2:1 ratio to receive an Absorb BVS (1322 patients) or an XV stent (686 patients).

The primary end point, which was tested for both non-inferiority and superiority, was Target-Lesion Failure (cardiac death, target-vessel myocardial infarction, or ischemia-

driven target-lesion revascularization) at 1 year.

N Engl J Med. 2015 Nov 12;373(20):1905-15

Target Lesion Failure @ 1Y:7.8% of patients in the Absorb group and in 6.1% of patients in the Xience group (difference, 1.7

percentage points; 95% confidence interval, -0.5 to 3.9; p=0.007 for noninferiority and p=0.16 for superiority).

N Engl J Med. 2015 Nov 12;373(20):1905-15

N Engl J Med. 2015 Nov 12;373(20):1905-15

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Days Post Index Procedure

(N=1623)All RVD ≥2.25 mm

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Device thrombosis within 1y occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13).

N Engl J Med. 2015 Nov 12;373(20):1905-15

N Engl J Med. 2015 Nov 12;373(20):1905-15

0%

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10%

0 100 200 300 400

Days Post Index Procedure

(N=1623)All RVD ≥2.25 mm

0.8% 0.5%

Def

init

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roba

ble

ST(%

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Device thrombosis within 1y occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13).

(N=375)Any RVD <2.25 mm

4.6%

1.5%

AbsorbXience

AbsorbXience

Def

init

e/ P

roba

ble

ST(%

)

Days Post Index Procedure

N Engl J Med. 2015 Nov 12;373(20):1905-15

0%

2%

4%

6%

8%

10%

0 100 200 300 400

Days Post Index Procedure

(N=1623)All RVD ≥2.25 mm

0.8% 0.5%

Def

init

e/ P

roba

ble

ST(%

)

Device thrombosis within 1y occurred in 1.5% of patients in the Absorb group and in 0.7% of patients in the Xience group (P=0.13).

(N=375)Any RVD <2.25 mm

4.6%

1.5%

Absorb BVSXV

Absorb BVSXV

Def

init

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roba

ble

ST(%

)

In this large-scale, randomized trial, treatment of noncomplex obstructive coronary artery disease with an everolimus-eluting bioresorbable vascular scaffold, as compared with an everolimus-eluting

cobalt–chromium stent, was within the prespecified margin for noninferiority with respect to TLF @ 1 year.

N Engl J Med. 2015 Nov 12;373(20):1905-15

A total of 480 patients were randomized (241 BVS vs. 239 CoCr-EES). The primary endpoint of in-segment LL @ 1 year was 0.19±0.38 mm for BVS vs. 0.13±0.38 mm for CoCr-EES

achieving non-inferiority of BVS compared with CoCr-EES BVS and CoCr-EES also had similar 1-year rates of TLF: 3.4% vs. 4.2%, p=0.62 and definite/probable scaffold/stent thrombosis

(0.4% vs. 0.0%, respectively; p=1.00)

400 patients were randomised in a 2:1 ratio to BVS (N=266) or CoCr-EES (N=134). The 2-year TLF rates were 7.3% and 3.8% in the BVS and CoCr-EES arms (p=0.18), respectively.

400 patients were randomised in a 2:1 ratio to BVS (N=266) or CoCr-EES (N=134). VLST beyond 1-year was observed in 1.6% of the BVS arm, while there was no VLST in the CoCr-EES arm.

TLF @ 1, 2 & 3 Years based on PSP Implementation in the ABSORB Trials

AB IIAB III

AB ExtendAB JapanAB China

AB IIAB ExtendAB JapanAB China

non-PSP: 11.9%

PSP: 5.4%

AB II

Scaffold Thrombosis @ 1, 2 & 3 Years based on PSP Implementation in the ABSORB Trials

AB IIAB III

AB ExtendAB JapanAB China

AB IIAB ExtendAB JapanAB China

non-PSP: 3.4%

PSP: 0.7%

AB II

2nd Generation Everolimus-Eluting Absorb BVS

GT1

Post-PCIData on file of

DESolveTMCX Novolimus-Eluting BRSNovolimus-eluting scaffold

Thickness: 120 μm

Crossing Profile: 1.3 mm

DESolve Cx TrialPrimary Endpoint @ 6m: Efficacy,

In-scafold LL= 0.18 ± 0.29 mm

Primary Endpoint @ 6m: Clinical,MACE: 0%

6m30d 12m 24m

DESolveTM NXT Novolimus-Eluting BRS

DESolve NXT TrialPrimary Endpoint @ 6m:

In-scafold LLL& TLF: TLR, MI, Cardiac Death

Secondary Endpoint:

TLF @ 30d, 1Y, 2Y, 3YIn-segment LLL

IVUS-derived in-scaffold %obstruction

OCT-derived strut coverage6m30d 12m 24m 36m

Fantom® Sirolimus-Eluting BRS

FANTOMII

Prim

ary

Endp

oint

: MA

CE

& L

L @

6m

Seco

ndar

y En

dpoi

nt: M

AC

E &

LL

@ 9

m

6 month Primary Endpoint(n=100)

MACE(%)

2.1%

LL(mm)

0.25 ± 0.40

9 month Secondary Endpoint

MACE(%)

Ongoing

LL(mm)

Ongoing

RENUVIA Everolimus-Eluting Abluminal Coating BRS

Data on file of

Material: PLLA

Design: Zig-Zag hoops

Thickness: 120-μm

Abluminal Everolimus Coating

RENUVIA EES

30 D

ays

90 D

ays

FAST FIM, Efficacy of RENUVIA BRS

Angiographic endpoint:In-scaffold Late Lumen Loss

Experimental Study

30 D

ays

OCT FIM: N=30

30d

6m

12m

24m-

60m

Conclusions:Although the promising field of VRT was designed to eliminate many of the long-term limitations ofcontemporary metallic drug-eluting stents, recent randomized trials have raised concerns related to therates of very late scaffold thrombosis and the degree of functional restoration following scaffoldresorption.

The increasing adoption of optimal scaffold deployment techniques including optimal lesionpreparation, precise vessel sizing and post-dilatation indicates that late and very late clinical events aredramatically decreased, encouraging the utilization of bioresorbable scaffolds for coronaryrevascularization in selected clinical subsets.

Further design iterations of current generation bioresorbable scaffolds are expected to improve clinicaloutcomes compared to current generation metallic drug-eluting stents, a hypothesis that remains to beelucidated following completion of the ongoing clinical studies utilizing 2nd generation poly-L-lactic acidscaffolds.