1. Bioresorbeerbare “stents”
Dokter Luc Janssens
Imeldaziekenhuis Bonheiden
Elewijt, 21 september 2013

2. Bioresorbable Vascular Scaffolds:
A New Paradigm in the Treatment of Coronary Artery Disease

3. PCI Historical Perspective
1977
Andreas Gruntzig performs the first PTCA in Zurich, Switzerland
1988
Julio Palmaz and Richard Schatz develop a stainless steel stent for coronary applications
Drug eluting stents are introduced to the European and U.S. markets
1977
Balloon Angioplasty (PTCA) 1
Bare Metal Stents (BMS) 2
Coronary Drug Eluting Stents (DES) 3
Researchers develop early concepts of bioresorbable devices aimed at functioning as a temporary scaffold in the coronary vessel
1983
1999
Japanese researchers implant bioresorbable PLLA scaffold in human coronary arteries (Igaki-Tamai device)
2003
Abbott Vascular establishes the BVS development team
2006
Abbott Vascular enrolls 30 patients in ABSORB, the first ever human clinical trial testing a fully bioresorbable drug eluting scaffold
The idea for developing a temporary coronary scaffold began in the 1980s

4. ABSORB EXTEND Clinical Results – MACE at 12 Months ‘
1977
2000
A.B. ,the 1st PTCA by Andreas Gruentzig on September 29, 1977, attended and spoke at the 30th Anniversary on September 30, 2007 in Zurich, an incredible tribute to the breakthrough made by Andreas 30 years ago1
In patients who did not suffer sub-acute closure due to dissections, or restenosis due to negative remodeling in the first few months, long term results following balloon angioplasty were very encouraging and durable, with loss in MLD not seen until 17 years post procedure2
1. Meier, B., N Engl J Med. 2001; 344:
2. Hatrick, R., et al. EuroIntervention. 2009;5:

5. Interventional cardiology treatment: a historical unmet need ‘
Success of early PCI treatment (POBA) has been demonstrated for as long as 17 yearsx
Long-term POBA
Serial Angiography Studies
1977 *
0.5 1
1.5 2
2.5 3
Baseline
Post
6-months
4.5 yrs
10 years
17 yrs
MLD (mm)
Guiteras Val
Hatrick
2000
Meier, B., N Engl J Med. 2001; 344:
POBA is limited by acute recoil, sub-acute closure, and dissections
Guiteras-Val, P., et al. Am J Cardiol. 1999;83: / Hatrick, R., et al. EuroIntervention. 2009;5:

6. The Clinical Need for a Bioresorbable Vascular Scaffold’
Rationale
Vessel scaffolding is only needed transiently*
Vision
Improve Long Term Outcomes for Patients by Leaving No Scaffold Behind1
Potential Benefits
Restore the vessel to a more natural state, capable of natural vascular function
Eliminate chronic sources of vessel irritation and inflammation
Vessels remain free for future treatment options
Reduce the need for prolonged DAPT2
Allows for use of non-invasive imaging techniques (CCTA)
Improve patient quality of life
*Serruys PW, et al., Circulation 1988; 77: 361. Serial study suggesting vessels stabilize 3-4 months following PTCA.
1 – Small platinum markers at scaffold edges remain for fluoroscopic landmarking. 2. The Absorb IFU indicates DAPT for a minimum of 6 months.

7. ‘Caged’ (Stented) Vessel’
Delayed Healing  Stent Thrombosis?
* uncovered struts1
Benign NIH
Neo-Atheroma  Stent Thrombosis?
In-Stent Restenosis
Late Acquired Malapposition  Stent Thrombosis?
1. Virmani, R. Tissue responses in pre-clinical models; CIT 2010
NIH: NeoIntimal Hyperplasia

8. Potential of a Fully* Bioresorbable Vascular Scaffold’
Benign NIH
Expansive Remodeling1
Late Lumen Gain
In-Scaffold Restenosis
Plaque Regression2
Since struts disappear, issues related to very late persistent strut malapposition and chronically uncovered struts become irrelevant
1Serruys, PW, ABSORB Cohort B 1-year results; ACC / 2Serruys, PW, et al. Lancet. 2009; 373:
*Small platinum markers at scaffold edges remain for fluoroscopic landmarking.
NIH: NeoIntimal Hyperplasia

9. The Clinical Need for a Bioresorbable Vascular Scaffold’
Rationale
Vessel scaffolding is only needed transiently*
Vision
Improve Long Term Outcomes for Patients by Leaving No Scaffold Behind1
Potential Benefits
Restore the vessel to a more natural state, capable of natural vascular function
Eliminate chronic sources of vessel irritation and inflammation
Vessels remain free for future treatment options
Reduce the need for prolonged DAPT2
Allows for use of non-invasive imaging techniques (CCTA)
Improve patient quality of life
*Serruys PW, et al., Circulation 1988; 77: 361. Serial study suggesting vessels stabilize 3-4 months following PTCA.
1 – Small platinum markers at scaffold edges remain for fluoroscopic landmarking. 2. The Absorb IFU indicates DAPT for a minimum of 6 months.

10. How Absorb Resorbs
Water in surrounding vascular cells and blood penetrates polymer matrix
Long polymer chains become shorter and shorter   
Initially, hydrolysis preferentially cleaves amorphous tie chains, leading to a decrease in molecular weight without altering radial strength
Tie chains
When enough tie chains are broken, the device begins losing radial strength
To understand how the device is able to maintain its strength for a period of several months, even while undergoing degradation, it is worth looking at how the degradation process works.
Degradation occurs by hydrolysis. Water in the surrounding vascular cells and blood penetrates into the polymer matrix and starts to cleave ester bonds in the long polymer chains, creating shorter and shorter chains, until ultimately monomer units and small oligomers diffuse out of the polymer matrix and are subsequently metabolized.
In the first few months, this degradation process causes a reduction in molecular weight, but the strength of the scaffold is not impacted. This is because water can only penetrate the amorphous phase of the polymer matrix, and the device gets its structural support and strength from the crystalline domains. It is only when enough of the amorphous tie chains that link the crystalline domains are hydrolyzed that the scaffold loses its strength.
Analogies: bridge supports, brick wall 
Support 
Molecular Weight
Mass Loss 1 3 6 12 18
24 Months

11. The Absorb BVS scaffold is replaced by functional cellular Matrix
As the polymer matrix becomes more porous, extracellular matrix material in the form of proteoglycan is able to penetrate into the spaces between polymer crystalline structures; eventually, the area becomes filled by cells

12. Resorption: Vascular Response
Absorb BVS
Resorption Site
Polymer is replaced by an increasingly cellular provisional matrix
1 month
6 months
12 months
24 months
30 months
36 months
42 months
XIENCE V
Representative photomicrographs of porcine coronary arteries, 2x, Movat’s pentachrome
Images on file with Abbott Vascular

13. Resorption: Vascular Response
Resorption Site
Absorb BVS
Polymer is replaced by an increasingly cellular provisional matrix
1 month
6 months
12 months
24 months
30 months
36 months
42 months
XIENCE V
Representative photomicrographs of porcine coronary arteries, 20x, Hematoxylin and Eosin
Images on file with Abbott Vascular

14. Absorb Conformability
Absorb provides better conformability compared to metallic platforms
88°
91°
Absorb BVS
Serruys, PW. , Seeing is believing: the clinical evidence so far; PCR 2010; J. Gomez-Lara, JACC Cardiovascular Interventions. 2010; 3:

15. Restore : Preliminary Evidence of Vasomotion Suggests Improved Long-term Outcomes1
6 Months1
12 Months2
24 Months3
ABSORB Cohort B1
ABSORB Cohort B2
ABSORB Cohort A
(N=15)
(N=6)
(N=19)
(N=13)
(N=9)
(N=7)
0.5
Vasodilation
(pre-drug infusion to post-drug infusion)
 in Vessel Diameter (mm)
Vasoconstriction
-0.5
Acetylcholine
Methergine -1
1. Adapted from Serruys, PW. ACC / 2. Adapted from Serruys, PW. ACC / 3. Adapted from Serruys, PW, et al. Lancet 2009; 373: B

16. Restore: Late Lumen Gain Offers the Potential for Reduced TLR*
Post-PCI
6 Months
2 Years
n = 33
n = 33
n = 33
ABSORB
Lumen
Area
 7.2%
Scaffold
Area
Cohort B
Lumen Area
6.53 mm2
6.36 mm2
6.85 mm2
Serial Analysis*
 1.7%
Late Loss = 0.19 mm
*Serruys, PW., TCT 2011 B

17. Current PCI Options for Treating CAD
There is still room for improvement
Serruys, PW. PCR 2010
Serruys, PW. PCR 2010 B

18. ABSORB EXTEND Clinical Results MACE at 12 Months
Intent to Treat (ITT) Analysis – Interim Snapshot
The datasets are from different trials and displayed for descriptive purposed only.
MACE: a composite of cardiac death, MI, and ischemia-driven TLR
Chevalier, ABSORB EXTEND 12-month outcomes in the first 450 patient enrolled, Rotterdam EuroPCR Focus on BVS 2013

19. The Absorb BVS System Meeting an unmet clinical need?
Rationale
Vessel scaffolding is only needed transiently*
Vision
Improve Long Term Outcomes for Patients by Leaving No Scaffold Behind1
Potential Benefits
Restore the vessel to a more natural state, capable of natural vascular function
Eliminate chronic sources of vessel irritation and inflammation
Vessels remain free for future treatment options
Reduce the need for prolonged DAPT2
Allows for use of non-invasive imaging techniques (CCTA)
Improve patient quality of life
*Serruys PW, et al., Circulation 1988; 77: 361. Serial study suggesting vessels stabilize 3-4 months following PTCA.
1 – Small platinum markers at scaffold edges remain for fluoroscopic landmarking. 2. The Absorb IFU indicates DAPT for a minimum of 6 months.

20. Absorb May be Especially Beneficial for Certain Patient Types
Young patients may need future interventions that can be complicated or compromised by a permanent implant
First time, young patients*
Patients at risk for future interventions
Bioresorbable vascular scaffolds will preserve more treatment options for future interventions
Non-invasive imaging for early and late follow- up is feasible with BVS
Non-invasive assessment of patients by MSCT
Population with nickel allergy is estimated to be 8.6% of the general population1 Allergic reactions to nickel and molybdenum released from stents may be one of the triggering mechanisms for in-stent restenosis2
Patients with metal allergy
*Young patient defined as <65 years of age / Thyssen et al. Contact Dermatitis 2007 / 2. Koster, Lancet, Vol 356, 12/2/00

21. It’s difficult to make predictions especially about the future Al Gore