Transcript Bioresorbeerbare *stents*

Dokter Luc Janssens
Imeldaziekenhuis Bonheiden
Elewijt, 21 september 2013
Bioresorbable Vascular Scaffolds:
A New Paradigm in the Treatment of
Coronary Artery Disease
1977
1988
2001 - 2003
Andreas Gruntzig
performs the first PTCA in
Zurich, Switzerland
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
Researchers develop early
concepts of bioresorbable
devices aimed1977
at
Balloon
functioning as a temporary
scaffold in the coronary
Angioplasty
vessel
(PTCA)
1983
Japanese researchers
Bare
implant bioresorbable
PLLA
scaffold
in
human
coronary
Metal Stents
arteries (Igaki-Tamai device)
(BMS)
1999
Abbott Vascular enrolls 30
patients in ABSORB, the first
Coronary
Drug
ever
human clinical trial
Abbott Vascular
a fully bioresorbable
establishes the BVS Eluting testing
Stents
drug eluting scaffold
development team
2003
(DES)
2006
 The idea for developing a temporary coronary scaffold began in the 1980s
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: 144-145.
2. Hatrick, R., et al. EuroIntervention. 2009;5:121-126.
 Success of early PCI treatment (POBA) has been demonstrated
for as long as 17 yearsx
Long-term POBA
Serial Angiography Studies
1977
3
(mm)
MLD
(mm)
MLD
2.5
2
1.5
*
Guiteras Val
Hatrick
2000
1
0.5
0
Meier, B., N Engl J Med. 2001; 344: 144-145
 POBA is limited by acute recoil, sub-acute closure, and dissections
Guiteras-Val, P., et al. Am J Cardiol. 1999;83:868-874. / Hatrick, R., et al. EuroIntervention. 2009;5:121-126.
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.
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
Benign NIH
Expansive Remodeling1
In-Scaffold Restenosis
Plaque Regression2
Late
Lumen
Gain
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 2011 / 2Serruys, PW, et al. Lancet. 2009; 373: 897-910.
*Small platinum markers at scaffold edges remain for fluoroscopic landmarking.
NIH: NeoIntimal Hyperplasia
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.
 Water in surrounding vascular cells and blood penetrates polymer matrix
 Long polymer chains become shorter and shorter


   
   
   
Tie
chains

Initially, hydrolysis preferentially cleaves amorphous tie chains, leading
to a decrease in molecular weight without altering radial strength

When enough tie chains are broken, the
device begins losing radial strength


Support




Molecular Weight

 


 

Mass Loss
1
3
6
12
18
24 Months
Resorption Site
Absorb BVS
1 month
Polymer is replaced by an increasingly cellular provisional matrix
6 months
12 months
24 months
XIENCE V
Representative photomicrographs of porcine coronary arteries, 2x, Movat’s pentachrome
Images on file with Abbott Vascular
30 months
36 months
42 months
Resorption Site
Absorb BVS
1 month
6 months
Polymer is replaced by an increasingly cellular provisional matrix
12 months
24 months
30 months
XIENCE V
Representative photomicrographs of porcine coronary arteries, 20x, Hematoxylin and Eosin
Images on file with Abbott Vascular
36 months
42 months
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: 1190-8.
12 Months2
24 Months3
ABSORB Cohort B1
ABSORB Cohort B2
ABSORB Cohort A
(N=15)
(N=6)
(N=19)
(N=13)
(N=9)
0.5
(N=7)
Vasodilation
6 Months1
0
-0.5
Acetylcholine
-1
Vasoconstriction
 in Vessel Diameter (mm)
(pre-drug infusion to post-drug infusion)
1
Methergine
1. Adapted from Serruys, PW. ACC 2011 / 2. Adapted from Serruys, PW. ACC 2011 / 3. Adapted from Serruys, PW, et al. Lancet 2009; 373: 897-910.
Post-PCI
6 Months
n = 33
n = 33
ABSORB
Cohort B
Serial Analysis*
Lumen Area
6.53 mm2
Scaffold
Area
 1.7%
6.36
mm2
n = 33
6.85
mm2
Lumen
Area
 7.2%
Late Loss = 0.19 mm
*Serruys, PW., TCT 2011
2 Years
There is still room for improvement
Serruys, PW. PCR 2010
Serruys, PW. PCR 2010
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
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.
Patients at risk for future
interventions
 Young patients may need future
 Bioresorbable vascular scaffolds will
interventions that can be complicated
preserve more treatment options for
or compromised by a permanent implant
future interventions
First time, young patients*
Non-invasive assessment
of patients by MSCT
 Non-invasive
imaging for early
and late followup is feasible
with BVS
Patients with metal allergy
 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
*Young patient defined as <65 years of age / 1. Thyssen et al. Contact Dermatitis 2007 / 2. Koster, Lancet, Vol 356, 12/2/00