1. BIOABSORBABLE VASCULAR
SCAFFOLD
WHERE ARE WE?
I.TAMMI RAJU

2. overview
• History & evolution of BVS
• Advantages
• Types of BVS
• Physiology of BVS
• Clinical trails of BVS
• Future perspectives of BVS

4. BVS , WHERE ARE WE

5. • First revolution- balloon
angioplasty
• The invention of balloon
angioplasty as a
percutaneous treatment for
obstructive coronary disease
by Andreas Gruntzig in
1977 was a huge leap
forward in cardiovascular
medicine and undoubtedly
will always be remembered
as a revolution in the field
of revascularization
BVS WHERE ARE WE

6. • In 1964, Charles Theodore Dotter and
Melvin P. Judkins described the first
angioplasty
• 1977, Andreas Grüntzig performed the
first balloon coronary angioplasty
Plain Old Balloon
Angioplasty(POB
A)
 Dissections – Focal to threatened
dissection
 Acute recoil
 Chronic constrictive remodeling

7. • second revolution -BMS
• The advent of BMS and the landmark Belgian-Netherlands Stent Study
(BENESTENT) and Stent Restenosis Study (STRESS) trials have
established BMS as the second revolution in interventional cardiology.
• A solution to acute vessel occlusion by
– sealing the dissection flaps and
– preventing recoil &
– making emergency bypass surgery a rare occurrence.
– Serruys PW, de Jaegere P, Kiemeneij A comparison of balloon-expandable-
stent implantation with balloon angioplasty in patients with coronary artery
disease: Benestent Study Group. N Engl J Med. 1994;331:489–495.
BVS , WHERE ARE WE

8. Plain Old Balloon
Angioplasty(POB
A)
Bare Metal
Stent(BMS)
• In 1986, first coronary stent by Sigwart et
al
• Gianturco-Roubin first FDA – BES – 1993
• Palmaz-schartz first STENT VS POBA

9. • Restenosis rates were further reduced from 32% to 22% at 7
months, but this rate was still high, and neointimal
hyperplasia inside the stent was even more prominent than
with angioplasty.
• Disadvantages (Because the vessel was now caged with metal)
– late luminal enlargement and
– advantageous vascular remodeling could no longer occur.
– late stent thrombosis (ST), was also first described.
– Serruys PW, Daemen J. Late stent thrombosis: a nuisance in both bare
metal and drug-eluting stents Circulation. 2007;
BVS , WHERE ARE WE

10. • Third revolution-DES
• The first 45 patients implanted with the sirolimuseluting Bx
velocity stent (Cordis, Johnson & Johnson, Warren, NJ) were
found to have negligible neointimal hyperplasia at follow-up.
• This was confirmed in the randomized comparison of a
sirolimus-eluting stent with a standard stent for coronary
revascularization (RAVEL) study.
– Morice MC, Serruys PW A randomized comparison of a sirolimus-
eluting stent with a standard stent for coronary revascularization. N
Engl J Med. 2002;346:
BVS , WHERE ARE WE

11. The RAVEL Study
A RAndomised (double blind) study with the Sirolimus
coated BX™ VElocity balloon expandable stent
(CYPHER™) in the treatment of patients with De Novo
native coronary artery Lesions
M.C. Morice, P.W Serruys, J.E. Sousa, J. Fajadet, M. Perin, E. Ban Hayashi, A.
Colombo, G. Schuler, P. Barragan, C. Bode
The treatment of a de novo lesion with CYPHER™ appears feasible and safe : no
acute, subacute (30 days) or late occlusion occurred although clopidogrel /
ticlopidine was administered for only 2 months
Virtual elimination of neo-intimal in-stent proliferation: MLD post deployment (2.43
mm) remains essentially unchanged at 6 months (2.42 mm) with no measurable late
loss (-0.05 mm) Restenosis (0%) and no evidence of edge effect

12. • Disadvantages
• Increased risk of late and very late ST.
• late ST rates of 0.53%/y, with a continued increase to 3% over 4 years.
– Late thrombosis in drug-eluting coronary stents after discontinuation of
antiplatelet therapy. Lancet. 2004
• In the (ARTS II) trial,with complex multivessel disease, the rate of
combined definite, probable, and possible ST was as high as 9.4% at 5
years, accounting for 32% of major adverse cardiovascular events
(MACEs).
– J Am Coll Cardiol. 2009
• Postmortem specimens of DES revealed significant numbers of uncovered
struts with persistent inflammation around the stent struts.
• Vasomotion testing demonstrated vasoconstriction to Ach.
– Vascular responses to drug eluting stents: importance of delayed healing.
Arterioscler Thromb Vasc Biol. 2007
BVS , WHERE ARE WE

13. ANGIOPLASTY

14. • Fully Bioresorbable Scaffold: The Fourth Revolution in
Interventional Cardiology?

15. POTENTIALADVANTAGE OF BRS
BVS , WHERE ARE WE

16. BVS , WHERE ARE WE

17. ADVANTAGES of BVS
• 1. A reduction in adverse events such as ST.
• Because drug elution and scaffolding are temporary and are
provided by the device only until the vessel has healed, no
foreign material such as nonendothelialized struts and drug
polymers (potential triggers for ST) can persist long term.
BVS , WHERE ARE WE

18. • 2.The removal, through bioabsorption, of the rigid caging of
the stented vessel.
• This can facilitate the return of vessel vasomotion, adaptive
shear stress, late luminal enlargement, and late expansive
remodeling.
• Furthermore, this might reduce the problems of jailing of the
ostium of side branches as seen with permanent metallic stent
struts.
BVS , WHERE ARE WE

19. • 3.A reduction in bleeding complications.
• No requirement for long-term dual antiplatelet therapy.
• This is particularly pertinent given that the elderly, who are at the greatest
risk of bleeding.
• Furthermore, early discontinuation of dual antiplatelet therapy with current
metallic DES,for whatever indication, has consistently been shown to be an
independent predictor of ST.
– Development and validation of a prognostic risk score for major bleeding in
patients undergoing percutaneous coronary intervention via the femoral
approach. Eur Heart J. 2007;
BVS , WHERE ARE WE

20. • 4.An improvement in future treatment options.
• The treatment of complex multivessel disease frequently results in the use
of multiple long DES; for example, in the synergy between percutaneous
coronary intervention with TAXUS and cardiac surgery (SYNTAX) trial,
the average number of stents was 4, and one third of patients had 100 mm
of stent implanted.
• In such cases, repeat revascularization is potentially challenging.
• The use of a BRS would mean that there would potentially be no restriction
on any future percutaneous or surgical revascularization should they be
needed.
BVS , WHERE ARE WE

21. • 5.Allowing noninvasive imaging (CT/MR angio.)
• Metallic stents can cause a blooming effect with these imaging modalities,
making interpretation more difficult.
• The (PLLA) scaffold should not restrict the use of CT or MRI because it is
nonmetallic; once bioabsorption has been completed with a BRS, it should
also not restrict the use of CT or MRI
• Noninvasive imaging follow-up could therefore become an alternative to
invasive imaging followup.
– Artifact-free coronary magnetic resonance angiography and coronary vessel
wall imaging in the presence of a new, metallic, coronary magnetic resonance
imaging stent. Circulation. 2005
BVS , WHERE ARE WE

22. • 6.Reservoir for the local delivery of drugs and genes.
• Because the duration of bioresorption is modifiable, according
to the type of polymers/copolymers, a tuned elution of
multiple drugs can potentially be achievable (eg, early elution
of antiproliferative agent from a coated polymer and long-term
elution of an antiinflammatory or other agent from the
backbone polymer).
BVS , WHERE ARE WE

23. • 7.Elimination of the concern that some patients have
at the thought of having an implant in their bodies for
the rest of their lives.(young individuals)
– Ormiston JA, Serruys PW. Bioabsorbable coronary stents.
Circ Cardiovasc Interv. 2009;2:255–260.
BVS , WHERE ARE WE

24. • VASCULAR REPARATIVE THERAPY
• On Premise that scaffolding & drug are only required on a temporary
basis following coronary interventions.
• Several studies support this concept and indicate that there is no
incremental clinical benefit of a permanent implant over time.
• The use of Absorb eliminates the presence of a mechanical restraint and
offers the potential of restoring natural vessel reactivity.
– Incidence of restenosis after successful coronary angioplasty: a time-related
phenomenon. A quantitative angiographic study in 342 consecutive patients at
1, 2, 3, and 4 months. Circulation, 1988.
BVS , WHERE ARE WE

25. • While stent performance is characterized by a single phase
(Revascularization), the performance of Absorb is governed by
three distinct phases:
– Revascularization
– Restoration
– Resorption.
• Together, these phases of Absorb performance deliver VRT

27. © 2010 Abbott Laboratories Pipeline product. Currently in development at Abbott Vascular. Not available for sale.
SE 2928803 Rev E
What is Required of a Fully Bioresorbable Scaffold to
Fulfill the Desire for ‘Vascular Restoration Therapy’?
Revascularization Restoration Resorption
0 to 3 months 3 to ~6-9 months + ~9 months +
Performance should mimic
that of a standard DES
Transition from scaffolding
to discontinuous structure
Implant is discontinuous
and inert
• Good deliverability
• Minimum of acute recoil
• High acute radial strength
• Controlled delivery of drug
to abluminal tissue
• Excellent conformability
• Gradually lose radial strength
• Struts must be incorporated
into the vessel wall (strut
coverage)
• Become structurally
discontinuous
• Allow the vessel to respond
naturally to physiological
stimuli
• Resorb in a benign fashion

28. © 2010 Abbott Laboratories Pipeline product. Currently in development at Abbott Vascular. Not available for sale.
SE 2928803 Rev E
What is Required of a Fully Bioresorbable Scaffold to
Fulfill the Desire for ‘Vascular Restoration Therapy’?
1 3 6 2 Yrs
Full Mass Loss &
Bioresorption
Mos
Platelet Deposition
Leukocyte Recruitment
SMC Proliferation and Migration
Matrix Deposition
Re-endothelialization
Vascular Function
Forrester JS, et al., J. Am. Coll. Cardiol. 1991; 17: 758.
Revascularization Restoration Resorption
Everolimus Elution
Mass Loss
Support
Oberhauser JP, et al., EuroIntervention Suppl. 2009; 5: F15-F22.

29. • Vessel Remodeling
• Through the use of the imaging modality intravascular ultrasound (IVUS),
data from the ABSORB Cohort B trial, reveals an increase in lumen area
between 6 months and 2 years.
• As Absorb resorbs, the vessel segment becomes unconstrained and there is
the potential for lumen gain.

30. • Vasomotion
• As Absorb resorbs, the treated vessel segment is able to react to changes in
blood flow and physiological stimuli that may occur with exercise or
certain drugs.
• By no longer supporting or caging the vessel, there is the potential for
allowing the vessel to respond naturally to physiological stimuli, which
could provide unique benefits.

31. • Restoration to a More Natural State with Absorb
• Another appealing long-term benefit of Absorb is the
possibility of progressive restoration of Absorb-treated vessel
segments to a more natural state as the polymeric scaffold
undergoes degradation.
– Restore vasomotor tone for regulation of coronary blood flow
– Restore vessel compliance and cyclic strain in response to pulsatile
flow
– Enable adaptive shear stress, allowing the vessel to regain its ability to
maintain quiescent homeostasis
– Permit accommodative, beneficial remodeling

32. Importance of Respecting Natural Vessel Curvature
Long-term flow disturbances
and chronic irritation can
contribute to adverse events
Gyöngyösi, M. et al. J Am Coll Cardiol. 2000;35:1580-1589.
Wentzel, J. et al. J Biomech. 2000;33:1287-1295.
91
88
Stiff Metal Stents BVS (Cohort B case)
Pre BVS Post BVS
Serruys, P. , TCT 2009
BVS appears to maintain natural
vessel curvature at implantation;
long-term, scaffold is fully resorbed

33. MECHANICAL CONDITIONING IN PRE-CLINICAL
MODEL (PORCINE)
Tests were performed by and data are on file at Abbott Vascular.
Transmission Electron Microscopy (TEM) Smooth Muscle -Actin
Dense
bodies
At 36 months, SMCs are well organized and have undergone
transformation to a functional, contractile phenotype
Mechanical
conditioning

34. • Fourth revolution
• All these problems promise to be solved with the advent of fully
biodegradable scaffolds.
• Offers the possibility of
– Transient scaffolding of the vessel to prevent acute vessel closure and
recoil &
– Transiently eluting an antiproliferative drug to counteract the
constrictive remodeling and excessive neointimal hyperplasia

35. • Development of BRS
• The efforts to create BRS started 20 years ago.
• The first experimental studies using a nonbiodegradable polyethylene-
terephthalate braided mesh stents in porcine animal models were published
in 1992.
• In 1996, it was reported in porcine coronary arteries negative
consequences after implantation of the Wiktor stent coated with 5 different
types of biodegradable polymers ,all resulting in marked inflammation
leading to neointimal hyperplasia and/or thrombus formation.
– Development of a polymer endovascular prosthesis and its implantation in
porcine arteries. J Interv Cardiol. 1992;5:175–185.

36. • Lincoff et al -- high-molecular-weight (321 kDa) PLLA was well tolerated
and effective, where as a stent coated with low-molecular-weight (80 kDa)
PLLA was associated with an intense inflammatory neointimal response.
• They also proved the feasibility of drug elution from the PLLA, although
no suppression of neointimal hyperplasia was reported.
-Lincoff AM, Schwartz RS, van Beusekom HM. Circulation. 1996;94:1690
–1697.
• In 1998, Yamawaki et al reported that in the porcine model the fully
biodegradable PLLA stent with tyrosine kinase inhibitor efficiently
suppressed proliferative stimuli caused by balloon injury.
– Yamawaki T, Shimokawa H, Kozai T. J Am Coll Cardiol. 1998;32:780
–786.
The technology failed to develop an ideal polymer that could limit
inflammation and restenosis and secondarily because of the growing
interest in metallic DES.

37. • The key mechanical traits for ideal material :
– High -elastic moduli to impart radial stiffness,
– Large -break strains to impart the ability to withstand deformations
from the crimped to expanded states, and
– Low -yield strains to reduce the amount of recoil and overinflation
necessary to achieve a target deployment.

38. • Numerous different polymers are available, each with different
chemical compositions, mechanical properties, and
subsequently bioabsorption times

40. • TYPES OF BVS

41. • first absorbable stent implanted in
humans,is constructed from poly-L-
lactic acid (PLLA).
• In the absorption process,
hydrolysis of bonds between
repeating lactide units produces
lactic acid that enters the Krebs
cycle
• first-in-man prospective,
nonrandomized clinical trial that
enrolled 50 patients a 4yr follow-
up of all the patients (100%)
revealed a low complication rate.
• loss index (late loss/acute gain) was
0.48 mm, which was comparable to
BMS, and demonstrated for the first
time that
• BRS did not induce an excess of
intimal hyperplasia Focus is now on
a peripheral application
Tamai H, Igaki K, Kyo E. Initial and 6-month results of
biodegradable
poly-L-lactic acid coronary stents in humans. Circulation. 2000
IGAKI-TAMAI BIOABSORBABLE STENT
BVS WHERE ARE WE

42. • Despite these impressive results, the failure of the stent to progress was
related primarily to the use of heat to induce self-expansion. There were
concerns that this could cause necrosis of the arterial wall, leading to
excessive intimal hyperplasia or increased platelet adhesion, leading to ST.
• Biodegradable peripheral Igaki-Tamai stents PERSEUS study,the stent
became available in Europe for peripheral use;
– Biamino G, Schmidt A, Scheinert D. Treatment of SFA lesions with PLLA
biodegradable stents: results of the PERSEUS Study. J Endovasc Ther.
2005;12:5.
BVS WHERE ARE WE

43. • The degradation of Mg produces
an electronegative charge that
results in the stent being
hypothrombogenic.
• Although the stent was
completely absorbed within 2
months, radial support was lost
much earlier so that, perhaps
within days, there was an
insufficient radial strength to
counter the early negative
remodeling forces after PCI.
• In addition, it did not release an
antiproliferative drug to counter
the intimal hyperplastic response
to stenting.
• Consequently, there was a high
restenosis rate at 4 months of
almost 50% and target vessel
revascularization at 1 year was
45% PROGRESS AMS trial: Lancet. 2007;369:1869 –1875.
BIOABSORBABLE MAGNESIUM STENT
BVS WHERE ARE WE

45. • It provides prolonged mechanical stability,
which has been achieved by using a
different magnesium alloy that has not only
a higher collapse pressure of 1.5 bar
compared with 0.8 bar for AMS-1 but also a
slower degradation time.
• In addition, the stent surface has been
modified; the stent strut thickness has been
reduced
• and the shape of the strut in cross section
has been altered from rectangular to square
(improving radial strength).
• These changes have prolonged scaffolding
and stent integrity, improved radial
strength, and reduced neointima
proliferation in animal models.
AMS-2
BVS WHERE ARE WE

46. • The AMS-3 stent (drug-eluting
AMS) is designed to reduce
neointimal hyperplasia by
incorporating a bioresorbable
matrix for controlled release of an
antiproliferative drug onto the
AMS-2 stent.
• Research is currently focused on
establishing the ideal drug
kinetics; initial animal trials have
demonstrated a sustained
antiproliferative effect at 1 month.
• A new clinical program resumed
in July 2010.
AMS-3 stent
BVS WHERE ARE WE

47. Stent:
Bioabsorbable
Magnesium Alloy
Discrete Drug
Delivery Reservoirs
Drug:
Pimecrolimus
Carrier:
Bioresorbable
Matrix
Modifications
BIOTRONIK DREAMS
Pimecrolimus-Eluting Stent System

49. REVA Endovascular Study of a
Bioresorbable Coronary Stent (RESORB) study

51. • More robust polymer, a spiral slide-and-lock mechanism to improve
clinical performance, and a coating of sirolimus (80% is eluted by 30 days
and 95% by 90 days.)
• The RESTORE Trial (Pilot Study of the ReZolve Sirolimus-Eluting
Bioresorbable Coronary Scaffold) is evaluating the safety and performance
of the first-generation ReZolve scaffold in 26 patients that were enrolled
2011 & 2012-F/u-5yrs.
• The ReZolve2 scaffold, a lower profile and sheathless version of the
original ReZolve scaffold, is being evaluated clinically in the RESTORE II
TriaL (IN 2013)
ReZolve stent.

52. Poly (Anhydride Ester) Salicylic Acid: The IDEAL Stent
both antiinflammatory and antiproliferative properties.

53. • Whisper trial, a stent with strut thickness of 200 m and a
crossing profile of 2.0 mm with a stent-toartery coverage of
65% was implanted in 8 patients.
• Because of higher-than-expected intimal hyperplasia, a
subsequent design iteration will have thinner struts, a higher
dose of sirolimus, and a lower percent wall coverage.

54. • The BVS stent design is characterized by a crossing profile of 1.4 mm with
circumferential hoops of PLLA.
• The struts are 150 m thick and are either directly joined or linked by
straight bridges.
• Both ends of the stent have 2 adjacent radiopaque platinum markers. The
radial strength = BMS.
• The backbone of the BVS device is made of semicrystalline polymer called
PLLA.
• The coating consists of poly D,L-lactide acid (PDLLA), which is a random
copolymer of D and L-lactic acid with lower crystallinity than the BVS
backbone.
• The coating contains and controls the release of the antiproliferative drug
everolimus.
Everolimus-Eluting PLLA Stent: BVS
Scaffold

55. BIORESORBABLE POLYMER
Everolimus/PDLLA Matrix
Coating
• Thin coating layer
• Amorphous (non-crystalline)
• 1:1 ratio of Everolimus/PLA
matrix
• Conformal Coating, 2-4 m
thick
• Controlled drug release
PLLA Scaffold
• Highly crystalline
• Provides device integrity
• Processed for increased radial
strength
Polymer backbone
Drug/polymer matrix

56. Absorb Design Elements

57. • Two versions of the stent have been developed.
• The design of the BVS stent Revision 1.0 consists of circumferential out-
of-phase zigzag hoops of PLLA with a strut thickness of 150 μm, linked
either directly or by straight bridges, with two radiopaque markers at each
end which enable a good visualization on angiography.

58. • The BVS Revision 1.1 consists of the same polymer, but different process
refinements allow the stent to increase its radial force, provide radial
support for a longer time, and, consequently, avoid the slightly higher, but
nonsignificant, recoil shown by QCA.
• MCUSA- This stent version has a different strut distribution, reducing the
maximum circular unsupported cross-sectional area, in contrast to BVS
Revision 1.0.
• It is currently under evaluation in the Cohort B of the non-randomized
ABSORB trial (NCT00856856) in 80 patients.

60. •Elixir’s proprietary fabrication and
processing technology allows for excellent
flexibility, deliverability, and well-apposed
struts that provide substantial radial
strength with low recoil.
•Performance has been evaluated in
clinical studies and has been shown to
provide excellent mechanical support,
even in highly tortuous vessels.
•More sizes.

63. • Bioresorption Process of PLLA
• In the PLA family of polymers, molecular-weight degradation
occurs in vivo predominantly through hydrolysis, which is a
bimolecular nucleophilic substitution reaction that can be
catalyzed by the presence of either acids or bases.
• The hydrolysis reaction in which water catalyzes a chain
scission event at an ester bond.

64. • From chemical standpoint, resorbable implants undergo 5
stages
• First stage is hydration of polymer.Starting at Hydrophilic (carboxylic
acid )end .
• second phase is depolymerization by hydrolysis. reduction in molecular
weight.
• Third stage- loss of mass (starts to fragment into segments of low-weight
polymer (radial strength reduces) .
• The fourth phase is assimilation or dissolution of the monomer by
Phagocytes
• Fifth-L-lactate is changed into pyruvate, which eventually enters the Krebs
cycle and is further converted into carbon dioxide and water.
– Handbook of Biodegradable Polymers. Boca Raton, FL: CRC Press;
1998.

65. REACTION PATHWAY FOR HYDROLYTIC DEGRADATION OF THE PLA
FAMILY OF POLYMERS.

66. • Poly-L-lactide is a semicrystalline polymer. The ordered polymer chains
constitute the crystalline component of the semicrystalline polymer, and the
random polymer chains form the amorphous segment
• In other words, the semicrystalline PLLA polymer is made of crystal
lamella (regions with high concentrations of polymer with crystalline
structure) interconnected by amorphous tie chains binding the crystallites
• Because the amorphous regions are less packed and therefore are more
accessible to water, more susceptible to hydration.

68. BVS WHERE ARE WE

70. Echogenicity analysis of BVS 1.0 after the procedure (BL) and at the 6-month
follow-up (FU). The polymeric strut was highly echogenic at baseline and thus
colored green by the dedicated echogenicity software. At 6 months, most struts
are no longer hyperechogenic (absence of green spots and prevalence of red
background), suggesting that the bioresorption has already occurred

71. Sequential changes in strain assessed by IVUS palpography. Prestenting shows a
long area of high strain (color coded for strain ranging from 1% to 2%); on a
single cross section, the high-strain region is located at the shoulder (7 to 8
o’clock) of the plaque. After scaffolding, abolition of this high strain spot is
documented. At 6 months and 2 years after scaffolding, high strain remained
absent.

72. IVUS virtual histology (IVUS-VH) images after the procedure and at 6 and
24 months after implantation of BVS 1.0, respectively. With IVUS-VH, the
struts were misclassified as dense calcium after the procedure and at 6
months, whereas at 24 months, they were no longer visible.

74. • Regulatory Status
• Absorb received CE Mark on December 14, 2010 for a limited
number of sizes. Additional sizes have received CE Mark on
August 13, 2012

75. • Implantation of Absorb
• Absorb is implanted into the patient’s coronary arteries via a percutaneous
intervention. The procedure of implanting an Absorb should only be
performed by physicians who have received appropriate training. The
implantation procedure of an Absorb is similar to a metallic stent; however,
additional attention is needed to ensure:
• Careful selection of the scaffold diameter for the target lesion reference
vessel diameter
• Thorough lesion preparation prior to scaffold implantation to optimize
scaffold deployment
• Safe advancement of Absorb across the lesion.

76. • Clinically Tested BRS

78. • ABSORB Cohort A
• A prospective, open-labeled, non-randomized, multi-center trial .
• The First in Man ABSORB trial represents the first clinical evaluation of
the safety and performance of the BVS Cohort A device. (n=30)
• In the ABSORB Cohort A trial, among 29 patients, the 5-year MACE rate
was low at 3.4%, due to only one ischemic MACE event (non-Q wave MI.)
that was reported within the first 6 months of the trial.
• There were no incidences of (ID-TLR).
• Additionally, there were no incidences of scaffold thrombosis or cardiac
death out to 5 years
ABSORB Trial Designs

79. ABSORB Cohort A
• N = 30; 6 sites* (Europe, New Zealand)
• Clinical follow-up schedule:
– 30 days, 6 months, 12 months, annually to 5 years
• Imaging schedule:
QCA, IVUS, OCT, IVUS VH Baseline
6 18 24
MonthsMonthsMonths
MSCT
(optional)
*Patients were enrolled in only 4 of 6 sites
Derived from Serruys, PW., AHA 2009.

81. Baseline
M2 1.0 mm/s
6 Month Follow Up
M3 1.0 mm/s
2 Year Follow Up
C7 20 mm/s
ABSORB Cohort A
Side Branch Preservation by Angio, and OCT

82. © 2010 Abbott Laboratories Pipeline product. Currently in development at Abbott Vascular. Not available for sale.
SE 2928803 Rev E
ABSORB Cohort A
Temporal Lumen Dimensional Changes, Per Treatment
ABSORB
Cohort A
Scaffold
Area
11.8% 17.2%
Post-PCI 6 Mos. 24 Mos.
n = 25
Late Loss = 0.43 mm
MLA = 5.09mm2 3.92mm2 4.34mm2
Late lumen loss at 6 months mainly due to reduction in scaffold area
Very late lumen enlargement noted from 6 months to 2 years
n = 25 n = 19

83. BVS Device Optimization Objectives
Cohort A
Cohort B
Photos taken by and on file at Abbott Vascular.
• More uniform strut distribution
• More even support of arterial wall
• Lower late scaffold area loss
― Maintain radial strength for at least 3 months
• Storage at room temperature
• Improved device retention
• Unchanged:
– Material, coating and backbone
– Strut thickness
– Drug release profile
– Total degradation Time
• More uniform strut distribution
• More even support of arterial wall
• Lower late scaffold area loss
― Maintain radial strength for at least 3
months
• Storage at room temperature
• Improved device retention
• Unchanged:
– Material, coating and backbone
– Strut thickness
– Drug release profile
– Total degradation Time

85. • ABSORB Cohort B
• The ABSORB Cohort B trial had two subgroups (B1 and B2) for follow-up
purposes as determined by protocol.
• 3-year follow-up data is available for Group B1 (n=45), and was recently
reported at the TCT 2012 meeting in Miami, Florida, USA
• In the ABSORB Cohort B trial, among 100 patients There has been no
reported scaffold thrombosis or cardiac death in the ABSORB Cohort B
trial to date, the 2-year ischemic driven MACE rate was 9.0%, due to 3
non-Q wave MIs and 6 ischemia driven target lesion revascularizations .

89. KM estimate of MACE rate in patients treated with Absorb BVS
(ABSORB Cohort B, n=101) vs. patients treated with a single 3.0x 18
mm metallic XIENCE V (SPIRIT FIRST+II+III, n=227)

91. • Clinical Procedure Success 98%
• ABSORB B Group 1 –MACE rate of 6.8% at 2 and 3 years (1
peri-procedural MI & 2 TLR)
• No additional MACE between 1 year and 3 years
• No scaffold thrombosis event
• Clinical data very comparable to Xience-V data from SPIRIT
I-III
CONCLUSION

92. • ABSORB EXTEND
• The ABSORB EXTEND trial is a continuation in the assessment of the
safety and performance of Absorb in a larger study.
• The lesions are longer than in the ABSORB Cohort A and Cohort B trials.
• Planned overlap of Absorb scaffolds during the procedure
• ABSORB EXTEND is a prospective, single-arm, open-label clinical study
that is planned to enroll up to 1,000 subjects at up to 100 global sites.
• Clinical follow-up is being planned on all subjects enrolled in the trial for
up to 3 years.

105. • ABSORB II: European Randomized Control Trial
• ABSORB II is a randomized, active-controlled, single-blinded, multicenter
clinical trial and will enroll approximately 501 subjects in 40 sites in
Europe.
• Aim: primary endpoints of vasomotion and change in lumen diameter.
• Subjects will be clinically followed at 30 days, 180 days, 1, 2, and 3 years
post-procedure
• Imaging studies will include angiography, IVUS/IVUS-virtual histology,
Lipiscan, (MSCT), all at 2 years with the option of 3 years pending 3-year
results from the ABSORB Cohort B trial.

106. • ABSORB III: US Randomized Controlled Trial for US Approval
• The ABSORB (RCT) is designed to evaluate the clinical safety and
efficacy of Absorb for US approval. in comparision with the XIENCE
family.
• The ABSORB III is a prospective, randomized, active-control, single-blind,
multi-center clinical trial that will register approximately 2,250 subjects in
up to 220 sites in the US and outside the US.
• A cohort of approximately 2,000 patients will be used for approval of
Absorb by the United States Food and Drug Administration (FDA).
Enrollment is planned for 2012/2013, pending US FDA approval.

107. • ABSORB IV: Randomized Controlled Trial for Landmark Analysis
• The ABSORB IV trial is similar in design to ABSORB III, and designed to
enroll approximately 2,500 to 3,000 patients with clinical follow-up out to
5 years.
• Clinical data from both ABSORB III and IV will be pooled to enable a
landmark analysis for 4,500 to 5,000 subjects to show superior safety and
benefits of Absorb compared to XIENCE.

108. • ABSORB Japan: Randomized Controlled Trial
• ABSORB Japan is a prospective, single-blind, multi-center randomized 2:1
trial of Absorb: XIENCE V involving up to 400 subjects in up to 35
Japanese sites to seek Japanese approval.
• The patient eligibility criteria are similar to the ABSORB III study.
• The primary endpoint is 1 year target lesion failure (TLF) showing non-
inferiority to XIENCE, with each subject returning for at least one imaging
follow-up involving one of the following modalities: angiography, IVUS,
and/or OCT.

109. • ABSORB China: Randomized Controlled Trial
• ABSORB China is a prospective, single-blind, multi-center randomized 1:1
trial of Absorb: XIENCE V involving approximately 400 subjects in up to
25 Chinese sites.
• The patient eligibility criteria are similar to ABSORB III.
• The primary endpoint is 9 months angiographic endpoint of in-segment
late loss, showing non-inferiority to XIENCE, for Chinese approval.
• Patients will subsequently return only for clinical follow-up out to 5 years.

110. • ABSORB FIRST: International Post-Market Registry
• The ABSORB FIRST Registry is designed to evaluate the safety and
clinical outcomes of Absorb in daily use in patients with de novo lesions in
previously untreated vessels.
• The ABSORB FIRST Registry is a single arm, prospective, international
post-market registry of patients with de novo lesions in previously
untreated vessels treated with Absorb per IFU (on-label use).
• The ABSORB FIRST Registry will enroll a minimum of 10,000 patients in
approximately 300 sites throughout multiple countries worldwide where
Absorb has regulatory approval and is commercially available. Enrollment
will be initiated in phases distributed over various regions/geographies
worldwide. One year follow-up will be conducted on all patients. Annual
follow-up visits will be conducted in subgroups of 1,000 patients each from
2 to 4 years.

111. TCT 2013

119. • First, the optimal duration of scaffolding with drug-elution should be
further elucidated.
• In both AMS-1 magnesium stent and BVS 1.0 scaffolds, late scaffold
shrinkage was one of major contributors to luminal loss.
• In a previous study with serial IVUS imaging after angioplasty or
directional coronary atherectomy,some positive remodeling occurred early
after the procedure up to 1 month, whereas the negative remodeling (eg,
decrease in external elastic lamina) occurred at 1 to 6 months
Future Perspectives

120. • This suggests that the need to prevent negative remodeling is necessary at
least until 6 months.
• This could be achieved by tuning the biodegradation speed in changing the
molecular weight of the polymer and increasing its crystallinity,thereby
prolonging the mechanical integrity of the scaffold.

121. • 2.BRS technologies without drug elution such as REVA and AMS-1 were
associated with high TLR rates.
• More specifically, in the AMS-1 trial, 45% of late luminal reduction was
attributed to neointimal hyperplasia at 6 months.
• These results suggest that the elution of antiproliferative agents might be
indispensable to make the BRS clinically applicable and efficient at
medium term.

122. • 3.The clinical advantage of BRS technology over the currently available
DES needs to be further investigated.
• BVS and Mg stents showed the recovery of responsiveness of the treated
vessel to vasoactive agents such as nitroglycerin.
• The restoration of vasomotion can indirectly stand for the completeness of
vessel healing; however, it is still unclear what the real clinical advantage
of this phenomenon is.
• In patients with early atherosclerosis, the presence of abnormal endothelial
function was associated with poor outcomes or more frequent angina.

123. • 4.A potential drawback of this new technology is strut fracture.
• Unlike metallic stents, the polymeric devices have inherent limit of
expansion and can break as a result of overdilatation.
• In an anecdotal case from the ABSORB cohort A, a 3.0-mm scaffold was
overexpanded with 3.5-mm balloon, which resulted in strut fracture as
documented with OCT.
• The clinical significance of such a case, evidenced only by OCT, needs to
be further elucidated, but undoubtedly fracture should be avoided by
respecting the nominal size of the scaffold.

124. • 5.Data transferability might be another issue from the regulatory
perspective.
• In conventional metallic stents, the essential component was platform,
coating, and drug.
• When it comes to BRS polymeric stents, even with the same PLLA and
design, the speed of biodegradation/bioresorption can be different
according to the manufacturing process of PLLA.
• For example, molecular weight can influence the degree of inflammation,
as shown in a previous preclinical study.
• Although the safety of PLLA is inferred from other medical application
such as orthopedics, orbital floor defects, and spinal surgery, each
scaffolding device implanted in the coronary circulation still needs to be
tested in terms of biocompatibility.

125. conclusion
• This technology is currently still in its infancy.
• However, the return of normal vascular function after
bioabsorption has opened a new horizon aimed at promoting
“vascular restoration therapy.”
• This therapy is an exciting development and certainly worthy
of the accolade of being the fourth revolution in
interventional cardiology

126. 150
THANK YOU