Download Alex (Balton, Poland)

Biodegradable Polymer DES Programs
Emerging Programs of DES
with Biodegradable
Polymers
Ricardo A. Costa, MD, PhD
Institute Dante Pazzanese, Sao Paulo, Brazil
Monday, Feb. 20th 2017 – 11:24 to 11:32 am (8 minutes)
Empire Ballroom – The Omni Shoreham Hotel
Washington, DC, USA
Disclosure Statement of Financial Interest
Within the past 12 months, I or my spouse/partner have had a
financial interest/arrangement or affiliation with the organization(s)
listed below.
Affiliation/Financial Relationship
Company
Grant/Research Support
Consulting Fees/Honoraria
Major Stock Shareholder/Equity
Royalty Income
Ownership/Founder
Intellectual Property Rights
Other Financial Benefit
Company Names
Company Names
Company Names
Company Names
Company Names
Company Names
Company Names
Conflict of Interest Statement
Ricardo A. Costa, MD, PhD
Research grant/consulting fees from Meril Life Sciences
Potential Advantages
• Avoid problems related to temporary or permanent
polymeric residue (late/very late recurrences, ST)
• Optimize vascular healing
• Maintain stent surface integrity (as opposed to
webbing/delamination seen with durable polymers)
• Shorten DAPT post-implant; thus, avoid bleeding
complications without compromising safety
• Maintain efficacy at inhibiting NIH
Emerging DES with BP
• Abluminus (Envision Scientific, India)
• Alex (Balton, Poland)
• BioMime (Meril Life Sciences, India)
• FireHawk (MicroPort, China)
• Inspiron (Scitech, Brazil)
• BuMA (SinoMed, China)
Emerging DES with BP
• Abluminus (Envision Scientific, India)
• Antiproliferative agent: sirolimus
• Combination of DES and BEB
• Biodegradable polymer matrix
• Completed released by 180 days
• 45” inflation time to ensure complete drug delivery
en-ABL 1 Clinical Trial - QCA Results*
Variable (40 pts/56 lesions) Baseline
Final
6-Month
-
-
Lesion length, mm
19.8±14.2
Reference diameter, mm
2.46±0.45 2.61±0.43 2.53±0.43
MLD, mm
0.71±0.39 2.40±0.40 2.17±0.54
%DS
71.8±14.6
6.9±6.7
14.1±14.4
-
-
0.24±0.30
Late lumen loss, mm
*Cardiovascular Research Center, São Paulo, Brazil
Sammer Dani @ TCT 2016
Sammer Dani @ TCT 2016
Sammer Dani @ TCT 2016
Sammer Dani @ TCT 2016
Sammer Dani @ TCT 2016
Emerging DES with BP
• Abluminus (Envision Scientific, India)
• Alex (Balton, Poland)
Alex Sirolimus-Eluting Stent
• Cobalt-chromium platform – 70 µm (Alex Plus – new design)
• Bioabsorbable polymer coating – 5 µm (PLGA, absorbed in ~8 weeks)
• Wide range of sizes (2.0-4.5 mm diameter; 8-40 mm length)
Dariusz Dudek @ TCT 2016
Dariusz Dudek @ TCT 2016
Dariusz Dudek @ TCT 2016
Dariusz Dudek @ TCT 2016
PI: Dariusz Dudek (Krakow, Poland)
Emerging DES with BP
• Abluminus (Envision Scientific, India)
• Alex (Balton, Poland)
• BioMime (Meril Life Sciences, India)
*Cardiovascular Research Center, São Paulo, Brazil
BioMime Morph Registry – Kuala Lampur
• 222 patients with diffused CAD treated with
Morph during Apr 2015 – September 2016
Baseline Characteristics
Age, ≤ 60 Years
Age, > 60 Years
Diabetes Mellitus (DM)
Hypertension(HTN)
DM + HTN
N = 222 (%)
144 (64.9%)
78 (35.1%)
56 (25.2%)
48 (21.5%)
104 (46.7%)
Procedural Information
Variable
N = 222 (%)
Vessel Treated with BioMime Morph
Sizes
N = 222 (%)
Diameters of BioMime Morph
LAD
127 (57%)
3.50 – 3.00 mm
68 (30.0%)
LCx
10 (5%)
3.00 – 2.50 mm
135 (60.8%)
RCA
84 (38%)
2.75 – 2.25 mm
19 (9.2%)
Lengths of BioMime Morph
Dilatation
N = 222, n (%)
30 mm
19 (8.0%)
Pre-Procedure
219 (98.7%)
40 mm
105 (47.5%)
Post-Procedure
222 (100.0%)
50 mm
34 (15.5%)
60 mm
64 (29.0%)
Antiplatelet Drugs
N = 222, n (%)
Aspirin + Clopidogrel
20 (54%)
Aspirin + Ticagrelor
17 (46%)
6 Months follow-up data
• 1 & 6 months clinical follow-up data
At Procedure
(N = 222)
1 month f/up
(N = 222)
6 month f/up
(N = 215)
0
0
0
No Complications
222 (100 %)
100 (100 %)
215 (96.8 %)
Stent Thrombosis
0
0
0
Bleeding
0
0
0
Death
Emerging DES with BP
• Abluminus (Envision Scientific, India)
• Alex (Balton, Poland)
• BioMime (Meril Life Sciences, India)
• FireHawk (MicroPort, China)
Key Components
Co-Cr stent
with abluminal grooves
Sirolimus
1/3 of
drug
dose
of
Cypher
D,L-PLA absorbed after 9 mo and
recover to metallic surface
Printing
technology
Stent Design - Isolated Abluminal Grooves
• One of the main components of Target Eluting Technology.
The grooves designed on the
outer surface of the stent allows
targeting release of the drug to
coronary vessel wall.
The depth of groove is about 1/3
of the strut, and the thickness of
coating stored in the groove is
about 10 microns (0.00039”)
TARGET Clinical Program
FIM
Enrollment
n=21
TARGET I Trial Enrollment
n=510
Workhorse Stent *
Randomized Trial
n=460
4mo Angio (95%)
and OCT (70%) F/U
XIENCE V
n=230
TARGET II Registry
Enrollment
n=730
Long FIREHAWK
(33 and 38mm) Registry,
n=50
FIREHAWK
n=230
9mo Angio F/U
(>=80%)
9mo Angio F/U
(>=80%)
1-Year Clinical F/U (>=95%) and Annually up to 5 Years (n=1,010)
Primary Clinical Endpoint: Device Oriented Composite of Cardiac Death, TVMI, or iTLR (Target Lesion Failure, TLF) at 1Year (Objective Performance Criteria)
Early healing proved by 4m OCT from
Target FIM study
Analyzed: 14 Stented Segments Every
0.3mm (1084 Cross-Sections), 11551 Struts
Proportion of Uncovered
and/or Malapposed Struts
Primary OCT Endpoint
443,
3.8%
300
250
2.2%
253
1.6%
200
179
150
11108, 96.2%
100
50
0.1%
11
Fully Covered
Uncovered and/or Malapposed
0
"Diamond"-Covered
Uncovered
Malapposed
TARGET All Comers – Clinical Trial Design
Open label, non-inferiority trial
All patients with symptomatic CAD
eligible for DES implantation
(no lesion/vessel limitations)
1,656 patients, 20 sites (Europe)
Subsets: QCA 176 pts; OCT 50 pts
100% monitoring
Firehawk Stent
n = 828
Xience EES
n = 828
Clinical/TLF
30d
Angio/OCT
6mo
50 Pts OCT Subset
12mo
13mo
2yr
3yr
4yr
176 Pts QCA Subset
Primary Endpoint: TLF (ARC defined) = Cardiac Death, Target Vessel MI, ID-TLR @ 12mo
Secondary Endpoint (powered): in-stent late loss @ 13mo; uncovered stent strut rate @ 3mo
Secondary Endpoints: TLF @ 30d, 6mo, 2 - 5 yr; Composite (all death, all MI, any revasc) at
each FU time point; QCA parameters @ 13 mo; OCT parameters @ 3 mo
Drug Therapy: ASA and thienopyridine > 6 months (per guidelines)
5yr
Emerging DES with BP
• Abluminus (Envision Scientific, India)
• Alex (Balton, Poland)
• BioMime (Meril Life Sciences, India)
• FireHawk (MicroPort, China)
• Inspiron (Scitech, Brazil)
Inspiron SES
Thin-Strut
Plataform
CoCr – L605
Abluminal Coating
Biodegradable Polymer
Low Drug
Sirolimus
Cronus Plus™
75 μm strut thickness
PLA + PLGA
Abluminal only
5 μm layer thickness
Complete degradation
in 6-9 months
Low dose
Inspiron™
Cypher™
3.5 x 13 mm
3.5 x 13 mm
56 μg
129 μg
INSPIRON I Trial
6-month angiographic and IVUS outcomes
EuroIntervention 2014;9:1380-1384
In-Stent late loss*
P < 0.001
1
IVUS % NIH Obstruction
P <0.001
0.84 ± 0.45
26.5 ±
11.4
30
20
0.5
10
0.22 ± 0.17
0
0
Inspiron Cronus
SES
BMS
7.8 ±
7.1
Inspiron
SES
*Primary EP
*Cardiovascular Research Center
São Paulo, Brazil
Cronus
BMS
DESTINY Trial
Study Design (Multicenter in 10 Brazilian Institutions)
170 patients (194 lesions)
Primary EP
IS LL at 9 months
Non-inferiority
Up to 2 de novo lesions
Vessels 2.5 – 3.5 mm
Single stent per lesion (up to 29 mm)
Randomization 2:1
Inspiron
(n=110 pts)
Biomatrix
(n=55 pts)
IVUS substudy*
(n=60 pts / 66 lesions)
OCTsubstudy*
(n=21 pts / 25 leions)
9-month angiographic follow-up*
(164 pts [96.5%] / 187 lesions [96.4])
*Cardiovascular Research Center, São Paulo, Brazil
DESTINY Trial
•
9-month QCA (in-stent)
.
Inspiron
Biomatrix
P
N
127
60
MLD, mm
2.44 ± 0.44
2.55 ± 0.40
0.09
DS, %
11.2 ± 11.3
9.7 ± 6.6
0.26
Late loss, mm*
0.20 ± 0.27
0.15 ± 0.20
<0.001
(NI)
Binary restenosis
3.2% (4)
1.7% (1)
0.56
*Study primary endpoint
DESTINY Trial
OCT Safety endpoints
Total of 8,944 struts analyzed [SES: 5,801; BES: 3,143]
P = 0.021
P = 0.198
2.38 ± 2.20
0.51 ± 1.00
0.28 ± 1.06
Uncovered Struts
Malapposed Struts
0.53 ± 0.81
DESTINY Trial
Clinical events (up to 270 days)
INSPIRON
(N= 111 Patients)
MACCE
MACE
Death
Emergent CABG
MI
TLR
TLR / TVR
BIOMATRIX FLEX
P-value
(N= 55 Patients)
7/111 (6.30)
4/55 (7.30)
0.672
7/111 (6.30)
4/55 (7.30)
0.672
0/111 (0.00)
0/55 (0.00)
NA
0/111 (0.00)
0/55 (0.00)
NA
5/111 (4.50)
3/55 (5.45)
0.803
3/111 (2.70)
1/55 (1.82)
0.690
6/111 (5.40)
1/55 (1.82)
0.269
Inspiron Registry
Baseline Clinical Characteristics (n=371 pts)
Male
63.3
Age, years
62.9 ± 10.6
Diabetes
50.7
Insulin-requiring DM
14.6
Acute coronary syndrome
39.6
Multivessel disease
69.2
2-vessel CAD
35.8
3-vessel CAD
33.4
Heart failure
15.6
Previous coronary treatment
48.5
Previous PCI
39.6
Previous CABG
18.1
Numbers are average ± standard deviation or percentages
CABG = coronary artery bypass graft surgery; CAD = coronary artery disease; DM = diabetes mellitus; PCI =
percutaneous coronary intervention
Inspiron Registry
Clinical Outcomes (n=371 pts; K-M estimates)
Mean 1.6 stents/pt (34.3 mm length)
30 days
180 days
0.8
1.6
4.0
-
0
1.3
0
2.8
Any major cardiac adverse event
4.6
9.0
Stent thrombosis
0.5
0.5
Possible
0
0
Probable
0.5
0.5
Definite
0
0
Overall death
Myocardial infarction
Peri-procedural
Non-peri-procedural
Target vessel revascularization
Emerging DES with BP
• Abluminus (Envision Scientific, India)
• Alex (Balton, Poland)
• BioMime (Meril Life Sciences, India)
• FireHawk (MicroPort, China)
• Inspiron (Scitech, Brazil)
• BuMA (SinoMed, China)
Conclusions
• New emerging DES with biodegradable polymer
technology incorporate advanced thin cobaltchromium platforms, abluminal coating and relatively
low drug dose (mainly sirolimus)
• Overall, all systems have demonstrated high efficacy on
inhibiting NIH and low event rates
• Comparative, non-inferiority studies evaluating their
performance and clinical impact in complex, real world
scenarios comparison to current gold standard DES
Thanks!