Transcript EGO-BioFreedom Study The first establishment of early healing profile & 9-month outcomes of a new “polymer-free” Biolimus-A9 drug-coated-stent by Longitudinal Sequential OCT Assessments: The EGO-BioFreedom.

EGO-BioFreedom Study
The first establishment of early healing profile &
9-month outcomes of a new “polymer-free”
Biolimus-A9 drug-coated-stent by
Longitudinal Sequential OCT Assessments:
The EGO-BioFreedom Study
Stephen WL LEE; Kelvin KW CHAN; Simon CC LAM; Shun-Ling KONG; Frankie CC TAM; Michael KL Wong; Anthony
YT WONG; Arthur SY YUNG; Catherine P SHEA; Li-Wei ZHANG; Yui Ming LAM; Gary Mintz*, Akiko Maehara*
Division of Cardiology, University of Hong Kong, Queen Mary Hospital, Hospital Authority, Hong Kong
* Columbia University Medical Center, Cardiovascular Research Foundation, New York, USA
Potential conflicts of interest
Speaker's name: Stephen Wai-luen LEE (Queen Mary Hospital, Hong Kong)
 I do not have any potential conflict of interest
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BioFreedom DES were provided by Biosensors Ltd. as an investigational device.
CRF Core Laboratory Analysis was supported by a limited grant from Biosensors Ltd..
EGO-BioFreedom Study
Study Aim
• DES reduce restenosis but require prolonged DAPT, with adverse development
of “late stent failure”. BMS may be preferred in some situations.
• Poor stent healing and late stent failure (thrombosis, late catch-up and
accelerated neo-atherosclerosis) have been reported to be associated with
polymer hypersensitivity and / or drug toxicity after DES implantation.
• The new “polymer-free” abluminally coated Biolimus-A9 BioFreedom Stent
(Biosensors Europe SA, Morges, Switzerland), with a stainless steel BMS
luminal surface was studied.
• A potential benefit of better early healing (as reflected by degree of rapid
early strut coverage by OCT) while retaining its efficacy as a DES (9M healing
and neointimal suppression).
• This study is a first of its kind for a polymer-free drug-coated stent using
longitudinal sequential OCT assessments.
EGO-BioFreedom Study
Novelty of stent design
Release kinetics: within
28 days 98% of BA9 would
be transferred to the
tissue of vessel wall; after
that essentially a BMS
120 micron thick
corrugated ring strut
Luminal surface: stainless
steel bare metal surface
Abluminal surface: “polymerfree” micro-structured crevices
harboring Biolimus drug (BA9)
BA9, a very high lipophilic
limus drug, allowing sustained
high tissue concentration for
neo-intimal suppression
BioFreedom Stent
• Prospective single center
Aims, Design & Methods
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N = 100 (20:20:20:20:20) patients
29% diabetic cases
Real world, all-comers except STEMI
Aims: To examine the benefits of the polymer-free BA9 Drug Coated Stent: •
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Early (1-5M) strut coverage: healing profile & guiding DAPT
9M OCT follow-up: neointimal metrics and morphology as a DES
Clinical outcomes (12 months)
Method:
3 Longitudinal sequential OCT assessments to monitor (a) progression
of strut coverage and (b) morphological changes of neointima.
* NIT, NIA, NIV denote neointimal thickness, area & volume by OCT
Study Flow Charts & Status
Baseline: 100 Patients
106 lesions (128 stents)
Mean stent length = 25.0±10.2mm
Mean stent diameter = 3.05±0.49mm
BioFreedom Stent Implantation
Baseline OCT for best stent optimization
1 month: 20 Patients
2 months: 20 Patients
3 months: 20 Patients
Patients randomly assigned to 5 groups (1:1:1:1:1 )
Early OCT assessment for early healing profile
4 months: 20 Patients
5 months: 20 Patients
9 months: 100 Patients
100% OCT FU rate
4 ISR (TLR rate 4%)
9-month OCT assessment for neointima metrics
Study Status: 100% OCT FU rate; study completed, pending core lab QCA results
6 Category Coverage Classification (CRF Core Lab., frame by frame analysis)
To ensure consistency & accuracy of visual assessment of early strut coverage !!
A = Definitely uncovered. Strut not covered by tissue and both sides appear square.
B = Uncovered with abnormal in-stent tissue (AIST). Strut covered by irregular tissue or fibrin, and both sides appear square.
C = Partially uncovered. Strut partially covered by tissue but only one side has a smooth continuous shoulder.
D = Covered (protruding). Strut covered by thin continuous tissue on both sides but still extending into the lumen.
E = Covered (embedded). Strut covered by continuous tissue or neointima, and not interrupting the smooth lumen contour.
F = Covered (proliferative). Strut covered with excessive growth of neointima with thickness > 0.3mm.
EGO-BioFreedom Study
Early Healing Curve (1-5 months Coverage %)
Percentage strut coverage (Cat. D, E, F)
increased progressively from 48.16%
(minimum) at 1M to 97.14% (median)
at 5M. In each group (20 patients) the
variations of coverage were much
higher in the earlier phases (1-2M),
which were largely replaced by near
complete coverage in the later months.
Early coverage is rapid with BF stents.
EGO-BioFreedom Study
Longitudinal Sequential OCT Assessments
Repeated Measures Mixed Model
OCT Frame Number analyzed
OCT Strut Number analyzed
Neointimal Thickness (NIT) (mm)
Mean Neointimal Area (NIA) (mm2)
Neointimal Volume (NIV) (mm3)
Percentage Neointimal Volume*
Median [Q1-Q3]
(Min, Max)
Median [Q1-Q3]
(Min, Max)
Median [Q1-Q3]
(Min, Max)
Median [Q1-Q3]
(Min, Max)
Median [Q1-Q3]
(Min, Max)
Median [Q1-Q3]
(Min, Max)
1-5 months
(Total Strut No. = 23351)
132 [104,164]
(70,350)
936 [719,1310]
(456,2516)
0.040 [0.030, 0.080]
(0.000, 0.930)
0.329 [0.135, 0.653]
(0.000, 2.179)
7.931 [3.259, 15.516]
(0.000, 100.616)
4.284 [2.143, 7.527]
(0.000, 20.827)
9 months
(Total Strut No. = 23239)
135 [106,161]
(72,333)
924 [723,1241]
(496,2378)
0.110 [0.060, 0.180]
(0.000, 1.540)
1.050 [0.672, 1.394]
(0.19, 3.916))
23.327 [13.722, 35.07]
(0.357, 124.682)
13.032 [9.940, 16.816]
(0.216, 37.851)
p-value
0.9111
0.6694
<0.0001
<0.0001
<0.0001
<0.0001
* Percentage Neointimal Volume = NIV/Stent Volume %
Early (1-5 Months) versus 9 Months Results:
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9 months median strut coverage reaches of 99.55% [IQR 98.17 - 99.93; min. 85.41, max. 100].
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More mature neointimal tissue (brighter and more homogeneous) was observed.
Median neointimal thickness (NIT) increased progressively from 1M to 5M at 0.04, 0.04, 0.04, 0.05, and
0.06mm, overall p=0.0028, respectively.
9M NIT remained very low at 0.10mm [0.06 - 0.18] confirming efficacy of BioFreedom as a DES.
In-stent percentage neointimal volume increased from 4.28% in early months to 13.03% at 9M.
Mean FU duration is 468±192 days to date; 4 patients had ISR at 9 months requiring treatment (TLR rate = 4%).
No other MACE recorded. No ARC (definite or probable) late stent thrombosis has been recorded to date.
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Representative cases
EGO-BioFreedom Study
Varying degree of coverage and changing neointimal morphology
Longitudinal Sequential OCT Assessments
Worse scenario (Group 2) 2 BF stents
Optimal baseline apposition
2M: some early coverage with
minor positive remodeling
9M: still inadequate coverage
with unhealthy neointima
Optimal baseline apposition
with some thrombi
2M: good early coverage
with young tissue
9M: fully covered struts
with healthy neointima
Optimal scenario (Group 2) 1 BF stent
EGO-BioFreedom Study
Thank you
Study Summaries
• With core lab. adjudication, the BA9 BioFreedom Stent is the first “polymer-free” drugcoated-stent ever studied, with early healing profile established and neointima
morphology changes over 9 months documented by longitudinal sequential OCT
assessments.
• Favorable 9M OCT changes and good 12M clinical outcomes were recorded without
occurrence of late stent thrombosis to date.
• This study is a proof of concept of the “polymer-free” approach (retaining neointimal
suppression efficacy like any other DES having various polymer design); this approach
could impose major impact on future new stent platform development.
• Establishment of early healing profile (early strut healing & coverage) could guide
optimal duration of DAPT (BF above 70% by 2 months), allowing physicians to treat
critically ill patients balancing stent thrombosis versus bleeding risk.
• Safety and efficacy: The polymer-free BioFreedom Stent appears to be a novel device in
terms of early stent healing and 9 months neointimal suppression. Limitations:- (a) no
control arm of another DES, and (b) need long-term clinical results for correlations.