BIORESORBABLE

VASCULAR SCAFFOLD
[Advantages, limitations and future directions]

HAFSA SHAHID
06331513005
Bioresorbable Vascular Scaffolds
Introduction
Bioresorbable vascular scaffolds (BVS) are designed to provide mechanical support and drug
delivery similar to the Drug Eluting Stent, followed by complete resorption over several
years. Recent trials have demonstrated clinical non-inferiority of the BVS compared with
contemporary DES, although certain clinical outcomes are concerning, particularly with
regard to higher rates of scaffold thrombosis. The theoretical long-term benefits are
promising, but remain unproven. Early adoption of this new technology in the United States
should apply the lessons learned regarding rigorous strategies to decrease adverse events,
including careful patient and lesion selection and meticulous implantation techniques.
Potential Advantages and Special Considerations

The ongoing quest for optimal coronary stenting provides further innovations in stent designs
and material properties utilizing biodegradable polymers or biocorrodible metals for
engineering coronary scaffolds. The impetus for developing drug-eluting bioresorbable
scaffolds (BRS) have been driven by the need for elastic and transient platforms instead of
stiff and permanent metallic implants in diseased coronary anatomies that enable prevention
of acute recoil or occlusion, allow sealing of post-procedural dissections following acute
barotrauma, and provide inhibition of the in-segment restenosis through efficient drug-
elution. After the acute revascularization and mid-term healing phase, the long-term
restoration phase follows as the biological elimination of the implanted scaffold is anticipated
over a three-year time interval. This technological endeavor promises to overcome long-term
implications of non-compliant metal caging over a pulsatile vascular tissue. Indeed, the
clinical endpoints following deployment of first generation drug-eluting BRS for
mechanically treating coronary artery disease are anticipated to be non-inferior when
compared with current-generation drug-eluting stents (DES), as well as the rates of late
clinical events attributed to either late restenosis (late catchup) or late and very late scaffold
thrombosis are expected to be reduced. Preliminary observations derived from multicenter
registries such as the ABSORB Cohorts A and B and ABSORB Extend,4 assessing the
clinical safety and efficacy of the Absorb™ BVS, as well as the BIOSOLVE-I5 and DeSolve-
1 studies which assessed the clinical safety and efficacy of the DREAMS-1 and DESolve
scaffolds have indicated the potentialities of these technologies.

Figure : BRS Family Illustrating the Major Clinical and Imaging Findings

PMA= pre market approval

TLR=target lesion revascularization

MACE= major adverse cardiovascular event (composite of cardiac death, myocardial

infarction, TLR)

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Physiologic Restoration (Restoration of Function)

The liberation of treated segment from its permanent metal cage will provide physiologic
recovery from both vasomotor function and vessel pulsatility through repaired endothelial
cell signaling and restored mechanotransduction {translation of mechanical forces in
chemical signals}. In addition to, the compensatory mechanisms of adaptive expansive
remodeling as well as the lumen gain will reactivated allowing a more physiologic response
to underlying flow-mediated stimuli.
Thrombogenic Risk Attenuation
The risk of late or very late scaffold thrombosis is expected to be eliminated following
scaffold degradation [platform + coating] by replacing the resorption sites [sites previously
occupied by polymeric struts] with connective tissue and minimizing the risk of late acquired
strut malapposition. Late or very late stent thrombosis remains a major concern with newer-
generation DES; while older-generation DES retain a stent thrombosis risk of 0.40.6%/year.6

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Elimination of the Risk of In-Scaffold Neoatherosclerosis and Its Clinical Implications
In-stent neoatherosclerosis had been observed with metallic DES and bare-metal stents
(BMS). Delayed endothelial healing associated with inefficient or sustained endothelial
dysfunction are the most prevalent precipitating mechanisms; meanwhile, the complete
mechanism of delayed plaque growth had not been fully elucidated. Despite the paucity of
long-term imaging data following BRS implantation, the combination of complete scaffold
resorption, regenerated intact endothelium with restored vasomotor function and plaque
passivation7,8 will potentially eliminate the risk and the subsequent clinical implications of
in-scaffold neoatherosclerosis.
Anatomic Restoration (Restoration of Form)
BRS are very compliant platforms compared to metallic stents, diminishing the extent of
disturbed flow patterns and associated vascular responses over the scaffolded segments and
the proximal and distal edges by limiting vascular straightening. Both vessel angulation and
curvature are anticipated to be restored by the time the scaffold eliminates its radial strength.
In addition to, any area/diameter mismatched causing step-up (proximal edge) or stepdown
(distal edge) regions, which generate local anatomic alterations with the subsequent
disturbances in fluid mechanics (wall shear stress) are expected to subside following scaffold
resorption.
A recent observation derived from the one-year interim analysis of the ABSORB II
randomized clinical trial, which compared a fully resorbable scaffold with a metallic stent
showed significantly reduced anginal episodes in patients treated with a biodegradable
scaffold. Although this preliminary observation indicates a new era of novel clinical
endpoints, further studies are needed to identify whether this is associated with the anatomic
and functional recovery of treated segments potentially linked to the restored fluid and solid
mechanical microenvironment following gradual scaffold resorption.9
Pediatric Applications
Absorbable scaffolds appear as more appropriate technologies for the treatment of pediatric
obstructive vascular lesions, such as aortic coarctation and pulmonary artery stenosis.
Permanent metallic implants limit vessel growth and require future surgical removal in
contrast to bioresorbable devices, which are able to allow natural vessel growth after the time
of radial strength elimination and further resorption.
Despite the overall encouraging results following deployment of BRS in non-complex lesions
of highly selective patients and the hypothetic beneficial properties over DES, the paucity of
randomized clinical trials with hard clinical endpoints (cardiac death, target vessel
myocardial infarction, or clinically-driven target lesion revascularization) following head-to-
head comparisons of BRS with current generation DES generated skepticism among the
interventional community. Only recently, the results of the first largescale ABSORB III
randomized clinical trial as well as ABSORB China and ABSORB JAPAN were reported and
solidified the merit of BRS technologies in the interventional treatment armamentarium.
ABSORB III is the largest multicenter randomized clinical trial and enrolled 2,008 patients
assigned in a 2:1 ratio to receive either an everolimus-eluting Absorb BVS or a cobalt-
chromium Xience stent. The primary endpoint of non-inferiority was target lesion failure

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(composite of cardiac death; target-vessel myocardial infarction; or ischemia-driven, target-
lesion revascularization) at one year, occurring in 7.8% in the Absorb BVS arm and in 6.1%
in the Xience arm (difference, 1.7 percentage points; 95% confidence interval, −0.5 to 3.9; p
= 0.007 for non-inferiority). Device thrombosis at one year among both arms was not
statistically different occurring in 1.5% of patients in the Absorb BVS arm versus 0.7% of
patients in the Xience group (p = 0.13).10
The ABSORB China trial was reported simultaneously with ABSORB III. Four hundred
eighty patients scheduled for elective percutaneous intervention were randomized in a 1:1
fashion to either Absorb BVS or Xience stent. The primary endpoint of in-segment late
lumen loss (LLL), which was powered for non-inferiority at one year was 0.19 ± 0.38 mm vs.
0.13 ± 0.37 mm (Pnon-inferiority = 0.01).11
Finally, the ABSORB Japan was another trial that enrolled 400 patients randomized in a 2:1
fashion to either Absorb BVS or Xience stent. The study met its primary endpoint of non-
inferior target lesion failure among the two arms at one year reaching 4.2% in the Absorb arm
versus 3.8% in the Xience arm. The secondary endpoint of in-segment LLL at one year was
0.13 ± 0.30 mm versus 0.12 ± 0.32 mm (Pnon-inferiority = 0.0001).12
ABSORB III, ABORB China, and ABSORB Japan proved the clinical safety and non-
inferior efficacy of Absorb BVS versus DES at one year. Although further improvements in
next generation BRS technologies are anticipated to meet superiority endpoints when
compared with current-generation DES, these data will most likely suffice for regulatory
approval in the U.S. and China.
Challenges and future directions
Deliverability and crossing profile
To provide sufficient hoop strength to oppose negative arterial remodelling and limit acute
recoil, polymeric scaffolds had thicker struts (typically 150–200 mm) than contemporary
metallic stents (80 mm). This, along with the other challenges in the crimping process, results
in larger crossing profile of polymeric scaffolds [1.4– 1.8 mm] than the contemporary DES
[1.0 mm]. The initial clinical studies have obviously restricted the use of BRS to simple
Type-A lesions. The role of PCI extends to complex lesions 71 and whether BRS can be used
for patients with complex lesions and tortuous or calcified vessels has largely remained
unexplored. Hence, concerns exist over deliverability and trackability of these devices.
Bioresorbable scaffolds have recently been used for PCI of the left main stem,72 small
diameter [≤2.5 mm] vessels,73 calcific lesions, long lesion with overlapping stents, in-stent
restenosis, bifurcations, and chronic total occlusions (Figures 5 and 6). However, further
work is needed to improve deliverability, pushability, and crossing profile without
compromising the radial strength.
Stretchability and strut fractures
Strut disruption with associated complications is potential concern. Magnesium BRS had
high tensile strength which can potentially offer good compliance of the scaffold without
exposure to the fractures during scaffold deployment.24 However, the polymeric devices
have inherent limit of expansion and can break as a result of over-dilatation. Although
radial strength of BVS has been reported to be comparable with metallic stents, this is true if

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the BVS is deployed within the limits of its size. If the BVS is over-stretched beyond its
designed limits, it may lose some of its radial strength and may indeed fracture.74 ReZolve
devices with the slide & lock design do not rely on deformation for scaffold expansion, so
mechanical strength is maintained during clinically relevant expansion range. DESolve
scaffold has the ability to self-appose to the vessel wall in the cases of minor malapposition
when expanded to the nominal diameter and a wide safety margin for expansion without strut
fracture.
It is essential to further improve this technology to enhance stretchability of the devices while
maintaining their radial strength. Currently, it is vital to appropriately size the reference
vessel and to respect the nominal size of the scaffold. It is important to have an adequate
lesion preparation before implantation of a BRS. Authors advocate a judicious use of pre-
dilatation, cutting/scoring balloons, rotational atherectomy etc., as needed, to ensure that
excessive post-dilatation is seldom required.
Side-branch occlusion
Current BRSs have thicker struts and higher scaffold to artery ratio, hence the concern over
side-branch occlusion. A post hoc angiographic assessment of 1209 side branches in 435
patients enrolled in the ABSORB-EXTEND, in comparison with 682 side branches in 237
patients treated with the everolimus-eluting Xience stent in the SPIRIT I and II trials, showed
a trend towards more side-branch occlusions in BVS-treated patients (BVS 6.0% vs.
XIENCE 4.1%, P¼0.09). Patients with post-procedural side-branch occlusion had higher
incidence of in-hospital MI(6.5 vs. 0.5%, P ,
0.01).MultivariableanalysisrevealedthatBVSimplantationwasanindependentpredictorofpost-
proceduralside-branchocclusion(oddsratio:2.1;95% confidence interval 1.2–3.7). By stratified
analysis, BVS demonstrated a higher incidence of post-procedural side-branch occlusion
compared with Xience only in small side branches with a reference vessel diameter of ≤0.5
mm (10.5 vs. 3.9%, P¼0.03 between the groups, p for interaction¼0.08).75 The effect of
implanting a BRS on future accessibility of side branch also remains unknown. As eluded
earlier, future development of BRS with thinner struts and reduced surface area of struts,
while maintaining mechanical strength, may potentially solve this issue.
Duration of dual antiplatelet therapy
The appropriate duration of DAPT for patients receiving BRS has not been investigated. It
could be argued that the duration of DAPT should be similar to metallic DES; however, due
to significant difference in strut thickness, concerns persist over early discontinuation of
DAPT. Certainly, the median duration of DAPT was .1 year in ABSORB Cohort B (97%
patients on DAPT at 6 months, 81% at 12 months,and25%at24months).Further studies
defining the duration of DAPT are warranted.
Use in acute coronary syndromes
The majority of PCI procedures are now carried out for acute coronary syndromes(ACS).
First-in-man for BRS devices were carried out in stable patients. Safety and efficacy data
for BRS use in ACS are not yet widely available. A recent small registry has suggested that
BVS may be used safely and effectively in patients with ST-segment elevation myocardial
infarction undergoing primary PCI.76 There are on-going studies (e.g. PRAGUE-19 trial and

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POLAR ACS registry) to further evaluate the use of BRS in ACS patients. Example cases of
ABSORB BVS use in ACS patients are shown in Figure 6.
Need for long-term safety and efficacy data
Limited data from very long-term follow-up of the IGAKI-TAMAI device have shown a
reasonable safety profile.77,78 Over 10-year follow-up of the first 50 patients (63lesions)
treated with 84 IGAKI TAMAI scaffolds has shown that TLR rates were16% at 1year,18%
at 5years,and 28% at 10years.Only two cases of definite ST(one subacute and one very late
which was probably related to a sirolimus-eluting stent implanted for a lesion proximal to an
IGAKITAMAI scaffold) were recorded. Survival rates free of death and cardiac death at 10
years were 87 and 98%, respectively.78 Furthermore, the data for 5-year follow-up of
ABSORB Cohort A and 3-year follow-up of ABSORB Cohort B also look very promising.
However, most of the data for BRS use are derived from small, non-randomized studies with
short- or mid-term follow-up and further studies are warranted. There are several clinical
trials and registries currently running on planned for further evaluation of BRS. The second-
generation DREAMSw is being tested in the BIOSOLVE-II study. The clinical trial with
ReZolve2 has also started in March 2013. The ART device is currently undergoing FIM trial
with the aim to complete recruitment of 30 patients in 2013. Amaranth has also just started a
FIM study to evaluate the safety and efficacy of its non-drug-eluting Fortitude TM device in
30 patients. ABSORB-EXTEND is an international prospective, single-arm study that will
recruit over 800 patients with more complex coronary disease than previously studied in the
ABSORB trial. The first patient was enrolled in January2010.In this study, a 2.5mm BRS is
also introduced, thus allowing for the examining the feasibility of BRS use in small vessels.
Additionally, patients with long lesions are not excluded, and hence it will be possible to
evaluate the potential safetyofoverlappingdevices.Interimresultsoffirst450patientsenrolled in
this trial have shown good safety and efficacy results at 12-month follow-up with 1 cardiac
death (0.2%), 13 cases of MI (2.9%), 8 cases of ischaemia -driven TLR (1.8%), 4 cases of ST
(0.9%), and a hierarchal MACE of 4.2%.79 Another study, ABSORB Physiology, is planned
to assess the acute and long-term effect of BVS compared with a conventional metallic DES,
in terms of impactonvascularcompliance,distensibility,endothelialresponsiveness and changes
in the shear stress distribution, after device/stent implantation,andat2-yearfollow-
up.TheABSORB-II is a prospective, randomized control trial that aims to compare the safety
and efficacy of the BVS1.1 vs. the Xiencew stentin 501patients with stable angina and 1–2
vessel disease randomized on a 2:1 basis.80 Clinical follow-up is planned at 30 and 180 days
and at 1, 2, and 3 years. All subjects will undergo coronary angiography and IVUS at
baseline (pre- and post-device implantation) and at 2-year follow-up. The primary endpoints
are the superiority of ABSORBBVS for vasomotion of the treated segment at 2 years and
non-inferiority for angiographic minimum lumen diameter at 2 years.