Bioabsorbable scaffold: Is it the stent of the future?

A\ Prof. Trương Quang Bình MD, PhD, FSCAI

University Medical Center

Coronary Stenting

Bioabsorbable scaffold

The vessel will be free of any caging

and can regain its normal function

BRSBRS technology is anticipated not

only to eliminate the risk of VLST, but

also to contribute to the restoration of

physiological function of treated

vessels.

VLST = Very Late Stent Thrombosis

Bioresorbable scaffolds (BRS)

ABSORB III

ABSORB III

ABSORB III

September 14, 2017

Magmaris Bioabsorbable scaffold: Is magnesium safer than polymer?

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Magnesium Backbone

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Thrombogenicity of the backbone

material

Resorption time Endothelialization Disturbance of the laminar blood

flow

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Porcine Shunt Model: Magmaris vs leading polymeric scaffold

Waksman R et al. Comparison of Acute Thrombogenicity for Metallic and Polymeric Bioabsorbable Scaffolds: Magmaris vs ABSORB in a Porcine Arteriovenous Shunt Model. Cardiovascular ntervention. Submitted for publication.

Platelet coverage marker:CD61 and CD42b for adherent platelets

1 hour

▪ Magmaris and the leading polymeric scaffold were implanted in a silicon tube

▪ The test was repeated with different scaffold positions.

▪ Both scaffolds were exposed to porcine blood flow for one hour.

▪ After one hour, platelet coverage of the scaffold surface was analyzed by using immunostaining

▪ Platelet coverage is directly involved in thrombus formation

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euro

FCR

Results Shunt Study 1:Magmaris vs. Absorb vs. Orsiro

Scanning Electron Microscopy■ Significantly less thrombus deposition in Magmaris compared to Absorb

■ Less inflammatory cells in Magmaris compared to AbsorbBioresorbable ScaffoldsMagmaris ABSORB Orsiro

Arrows: thrombus deposition, arrowhed: inflammatory cells

Adherent Thrombi

Inflammation

Waksman R. et al., In press Circulation Cardiovascular Intervention

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Magnesium Backbone

Thrombogenicity of the backbone

material

Resorption time

Endothelialization Disturbance of the laminar blood flow

Polymeric and Mg scaffolds in the same patient

Mg scaffold@ 18 months(RCA)

Polymeric scaffold@ 18 months

(LCX)

EuroPCR 2016 «Technical and procedural aspects» presented by Ralph Tölg, MD; Segeberger Kliniken, Bad Segeberg, Germany

▪ Low risk of late scaffold thrombosis due to fast resorption

▪ ~95% of magnesium is resorbed at 12 months.1

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Magnesium Backbone

Thrombogenicity of the backbone

material

Resorption time Endothelialization Disturbance of the laminar blood flow

En

do

thelialisa

tio

n[%

]Magmaris vs Absorb endothelialisation in

rabbit model at 28 days

euro

FCR

120

100 -80

-60 -40 -

20 -0 -

p<0.004

Above struts In between

struts

p = 0.007

Overall

PLLA BRS

Waksman R. et al., EuroIntervention 2017; published online ahead of print

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Magnesium Backbone

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Thrombogenicity of the backbone material

Resorption time Endothelialization

Disturbance of the laminar blood flow

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Computer simulation: Impact of recoil on the hemodynamic flow

1 Schmidt W et al. In vitro performance investigation of bioresorbable scaffolds - Standard tests for vascular stents and beyond.Cardiovascular Revascularization Medicine. 2016; 17(6):375-383.2 Foin N et al. Incomplete Stent Apposition Causes High Shear Flow Disturbances and Delay in Neointimal Coverage as a Function of Strut to Wall Detachment Distance, DOI: 10.1161/CIRCINTERVENTIONS.113.0009313 Kolandaivelu K et al “Stent Thrombogenicicty Early in High-Risk Interventional Settings Is Drive by Stent design and Deployment and Protected by Polymer-Drug Coatings” DOI:10.1161/CIRCULTATIONAHA.100.0032104 Jiménez J.M., Davies P.F. Hemodynamically Driven Stent Strut Design. Annals of Biomedical Engineering. 2009

▪ Magmaris showed no recoil increase, whereas the leading polymeric scaffold diameter decreased >20% within 1st hour in a bench test.1

Magmaris Leading polymeric scaffold

Magmaris Leading polymeric scaffold

At implantation 1h after implantation

more recoil

Inactive plateletsActivated platelets

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Magmaris has a potential low scaffold thrombosis risk

Mg

Low risk of thrombus formation due to 20% less recoil1 and therefore less platelet activation

Low risk of thrombus formation in a pre-clinical shunt trial

Low risk of late scaffold thrombosis due to fast resorption:~95% magnesium is resorbed at 12ms

Low risk of thrombus formation due to 15% better endothelialization

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Magmaris clinical program

BIOSOLVE–I46 EU

+ Switzerland

FIM TLF at 6 and 12 months

Completed

BIOSOLVE–IV1065 Worldwide PMS

Registry

TLF at 12 months

BIOSOLVE–II123 Worldwide In-segment LLL

at 6 months24 months FU

available

FIM

BIOSOLVE–III61 EU

+ Switzerland

In hospital Procedural success

6 months FU available

Pivotal trial

Enrolling

24

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Magmaris Clinical Trials

1 BIOSOLVE-II 6m 2 BIOSOLVE-II 12m

No definite or probable late1 or very late2 scaffold thrombosis was observed with Magmaris in clinical trials up to 12 months

Time 6 month 12 month

StudyBIOSOLVE II

n=123BIOSOLVE II

n=123

TLF [%] 3.3 3.4

Definite or probable ST [%] 0% 0%

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Magmaris clinical trials

1 BIOSOLVE-II and –III; 2 BIOSOLVE-II; 3 Haude M et al. Sustained safety and clinical performance of a drug-eluting absorbable metal scaffold up to 24 month: pooled outcomes of BIOSOLVE-II and -III. EuroIntervention. 2017; Accepted for Fast Track Publication.

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No definite or probable late1 or very late2 scaffold thrombosis (ST) was

observed with Magmaris in clinical trials up to 24 months.3

Time 6 months 24 months

StudyBIOSOLVE-III3

n=63BIOSOLVE-II3

n=123

TLF 3.3% 5.9%

Definite or probable ST 0% 0%

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CONCLUSIONS▪ Magmaris:

(1) material with low thrombogenic,

(2) resorption faster,

(3) Endothelialization better, and

(4) less recoil and less platelet activation.

▪ Magmaris in Biosolve I, II, III: probable or definite ST 0% at 12 and 24 months follow up; Biosolve IV: safe

▪ Magmaris, with magnesium backbone, will be safer than BRS with polymer backbone =>will be the Stent of the future?

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Thank you !