Download Late lumen loss (mm)

POLYMER-FREE BIOLIMUS A9-COATED STENTS IN
THE TREATMENT OF DE-NOVO CORONARY LESIONS
WITH SHORT DAPT: 12 MONTH CLINICAL FOLLOWUP OF THE PROSPECTIVE, MULTICENTER
BIOFREEDOM USA CLINICAL TRIAL
Ron Waksman, MD FACC, FSCAI, FESC
Professor of Medicine, (Cardiology) Georgetown University
Director, Cardiovascular Research Advanced Education
On behalf of the BioFreedom Investigators
MedStar Cardiovascular Research Network
MedStar Heart and Vascular Institute
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
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Grant/Research Support
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Consulting Fees/Honoraria
Company
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Boston Scientific
Biotronik
Biosensors
Astra Zeneca
Medtronic Vascular
Abbott Vascular
Symetis
Med Alliance
LifeTech
Amgen
The BioFreedom™ Drug-Coated Stent
The Concept
Curved Connectors
Unique Quadrature Link™ design
Different models for small and large vessels
Larger Side Branch Access
Optimized cell design providing a larger cell diameter
Biolimus A9™
Biosensors’ Proprietary Drug
• Rapamycin derivative specifically
developed for stent application
• Highest lipophilicity of all
common -limus drugs
• Rapid transfer into vessel wall
tissue (~ 28 days)
• Very long local residence time in
vessel wall tissue (several months)
• These Unique drug properties are
key to BioFreedom™ DCS design
Study Aim
Study Endpoints
Primary Safety Endpoint: The occurrence of major adverse cardiac
events (MACE) within 9 months following the implantation.
Primary Effectiveness Endpoint: In-stent late lumen loss at 9 months
(comparison vs. historical control: 0.41 ± 0.56mm*)
Secondary Endpoints:
 All cause mortality and target vessel revascularization at 9 months
 MACE, death, cardiac death, myocardial infarction, stent
thrombosis, ci TLR, ci TVR at 12 months, 24 months, 36 months
 Sub-group analysis (IVUS): Neointimal hyperplastic volume, %
volume obstruction at 9 months measured by IVUS
* Escolar E, Mintz GS, Popma J et al. Meta-Analysis of Angiographic vs Intervascular
Ultrasound Parameters of Drug Eluting Stent Efficacy from Taxus IV, V, and VI. Am J Cardiol,
2007: 100:621-6
BioFreedom™ USA
Study Organization
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First Safety and Feasibility Study of the BioFreedom™ stent
conducted in the USA (Feasibility IDE Study) NCT 02131142
Sponsor: Biosensors Research USA. Inc.
Manufacturer: Biosensors Interventional Technologies, Singapore
10 clinical study sites in the United States
Monitoring, data coordination and management, statistical
analysis and angiographic and IVUS core-labs: MedStar
Cardiovascular Research Network, Washington DC
Principal Investigator: Dr. Ron Waksman
Main In- / Exclusion Criteria
Inclusion criteria:
• Patients with coronary artery disease
• Must have angina pectoris, silent ischemia, or a positive functional study
• De-novo lesions ≤ 27mm length in native coronary arteries >50% stenosis,
abnormal FFR, or positive stress test
• TIMI flow of ≥ 2;
• One or two lesions in different vessels;
• Target vessel RVD must be ≥ 2.25 mm and ≤ 4.0 mm
Exclusion criteria:
• Acute MI < 72 hours, ACS < 9 months, LVEF <30%
• Not eligible for DAPT cessation at 3 months
• Bleeding, prior stroke, peptic ulcer or GI bleed <6 months
• Previous or planned other PCI within 30 days
• Crea >2.5mg/dL
• Previous stent or 2nd lesion in target vessel
• Left main, ostial or bifurcation lesions, CTO
• Severely calcified lesion
• > 1 stent needed to cover lesion
Study Design
De Novo Native Coronary Lesions
Vessel Diameter: 2.25–4.0 mm
Lesion Length: ≤ 27 mm
September 2014 – February 2015
Main Cohort
N=72
Exclusion
Total N= 3344
Follow up - IVUS Subgroup
Planned up to 30
3, 4, and 6 months
9 mo Angio alone
N=38
9 mo Angio/IVUS
N=26
Paired N = 25
Top 5 Exclusions: N= 1880
Prior ACS < 9 months: N = 487
Refusal to participate: N = 394
Unable to stop Clopidogrel at 3 months: N = 374
MI within 72 hrs: N = 327
Clean Cath: N = 298
PRIMARY ENDPOINT:
In-stent late lumen loss at 9 months* in 9M cohort
Key 2˚ Endpoints:
Major Adverse Cardiac Events (MACE)
QCA / IVUS Endpoints:
% diameter stenosis, in-segment late lumen loss, NIH volume and % volume obstruction
DAPT Regimen:
ASA indefinitely and clopidogrel for 3 months
NCT 02131142
*Compared to 0.41 ± 0.56mm according to Escolar E, Mintz GS, Popma J et al. Meta-Analysis of Angiographic
vs Intervascular Ultrasound Parameters of Drug Eluting Stent Efficacy from Taxus IV, V, and VI. Am J Cardiol,
2007: 100:621-6
BioFreedom Sites
Primary Investigator
Total
Enrolled
Washington Hospital Center, Washington, DC
Ron Waksman, MD
13
St. Joseph Medical Center/Berks Cardiology, Wyomissing, PA
Guy N. Piegari, MD
20
Mercy St. Vincent Medical Center, Toledo, Ohio
Ameer Kabour, MD
13
Cardiac & Vascular Research Center of Northern Michigan,
Petoskey, MI
Louis Cannon, MD
11
NC Heart and Vascular Research-Rex Hospital, Raleigh, NC
George Adams, MD
3
Dean J. Kereiakes, MD
1
John Wang, MD
7
Srinivas Addala, MD
1
Our Lady of Lourdes Medical Center, Voorhees, NJ
Anthony Smeglin, MD
1
Jewish Hospital and Saint Mary's Healthcare, Louisville, KY
Naresh Solankhi, MD
2
Site
The Carl & Edyth Lindner Center for Research and Education at
The Christ Hospital, Cincinnati, Ohio
MedStar Union Memorial Hospital, Baltimore, MD
MedStar Southern Maryland Hospital Center, Clinton, MD
Baseline Characteristics
Variable
Age (years) – mean ± SD
BMI – mean ± SD
Sex (male)
Diabetes
Insulin Dependent DM
Hypertension
Hypercholesterolemia
Peripheral Vascular Disease
History of Smoking (Any)
Current Smoking
Family History of CAD
History of Stroke
Congestive Heart Failure
History of Bleeding Diathesis
Active Bleed or Peptic Ulcer GI Bleed
History of Cancer
Chronic Renal Insufficiency
Prior CABG
Prior PCI
Prior MI
Prior COPD
In comparison to like trials
Count (%) or mean
63.5 ± 9.0
32.4 ± 6.8
57/72 (79.2%)
23/72 (31.9%)
12/73 (16.7%)
62/72 (86.1%)
63/72 (87.5%)
4/72 (5.6%)
40/72 (55.6%)
19/72 (26.4%)
40/65 (61.5%)
3/72 (4.2%)
3/72 (4.2%)
3/72 (4.2%)
0/3 (0.0%)
15/72 (20.8%)
7/72 (9.7%)
3/72 (4.2%)
23/72 (31.9%)
11/71 (15.5%)
8/72 (11.1%)
Clinical Presentation
Variable
Angiographic Inclusion Criterion
Target Lesion Stenosis >70%
Target Lesion Abnormal FFR
Target Lesion Abnormal Stress Test
Index Angina Status
Stable
Unstable
No angina
CCS Angina Class
Any angina
III or IV
Atrial Fibrillation at Baseline
Warfarin at Baseline
Other Anticoagulants at Baseline
Count (%)
71/72 (98.6%)
20/72 (27.8%)
53/72 (73.6%)
37/60 (61.7%)
23/60 (38.3%)
12/72 (16.7%)
60/71 (84.5%)
37/71 (52.1%)
3/71 (4.2%)
2/66 (3.0%)
8/72 (11.1%)
Lesion Characteristics - QCA
Variable
RCA
LAD
LCX
Proximal
Mid
Calcification (moderate/severe)
Lesion Class (ACC/AHA)
A
B1
B2
C
TIMI Flow
0/1
2
3
Thrombus
Variable
TIMI Flow
0/1
2
3
Thrombus
Pre-Procedure (n= 83)
26/83 (31.3%)
30/83 (36.1%)
27/83 (32.5%)
30/83 (36.1%)
43/83 (51.8%)
7/83 (8.4%)
13/81
31/81
19/81
18/81
(16.1%)
(38.3%)
(23.5%)
(22.2%)
0/83 (0%)
4/83 (4.8%)
79/83 (95.2%)
0/83 (0%)
Post-Procedure (n=83)
0/83 (0%)
2/83 (2.4%)
81/83 (97.6%)
0/83 (0%)
Procedural QCA Measurements
Parameter
Pre-procedure (n = 83)
Lesion Length (mm)
Reference vessel diameter (mm)
MLD (mm)
Diameter stenosis (%)
Post-procedure (n = 83)
Reference vessel diameter (mm)
Stent length (mm)
In-stent
MLD (mm)
Diameter stenosis (%)
Acute gain† (mm)
In-segment
Length (mm)
MLD (mm)
Diameter stenosis (%)
Acute gain (mm)
Mean ± SD, (median)
10.78 ± 4.67 (9.92)
2.67 ± 0.55 (2.68)
0.89 ± 0.34 (0.86)
65.99 ± 13.46 (67.98)
2.65 ± 0.59 (2.56)
15.59 ± 4.49 (15.18)
2.49 ± 0.52 (2.50)
4.97 ± 12.62 (6.67)
1.6 ± 0.51 (1.60)
24.03 ± 5.09 (24.01)
2.24 ± 0.54 (2.21)
15.22 ± 10.73 (14.86)
1.35 ± 0.55 (1.32)
QCA 9 Months
9 months (n=75) Morphology
TIMI Flow
0/1
2
3
Thrombus
9 months (n=66) Qualitative Measurements
Reference vessel diameter (mm)
In-stent
MLD (mm)
Diameter stenosis (%)
Late lumen loss (mm)
Binary restenosis (%)
In-segment
Length (mm)
MLD (mm)
Diameter stenosis (%)
Late lumen loss (mm)
Binary restenosis (%)
Mean ± SD, (median)
2/75 (2.7%)
1/75 (1.3%)
72/75 (96.0%)
0/75 (0%)
2.56 ± 0.66 (2.53)
2.15 ± 0.71 (2.29)
16.19 ± 23.29 (12.04)
0.32 ± 0.53 (0.19)
6.15 % (4/65)
24.09 ± 5.76 (24.43)
1.89 ± 0.68 (1.90)
26.68 ± 19.92 (22.69)
0.34 ± 0.51 (0.24)
7.69% (5/65)
Primary Endpoint
In-Stent Late Loss at 9 Months
Parameter
In-stent
Late lumen loss
†Compared
Statistics
Lesions at Follow up
(n = 66)
P†
Mean ± SD
0.32 ± 0.53
0.186
95% CI
0.19 - 0.45
Min-Max
-0.38 - 2.34
Median
0.19
Q1-Q3
0.08 - 0.38
to 0.41 ± 0.56mm according to Escolar E, Mintz GS, Popma J et al. Meta-Analysis of Angiographic vs
Intervascular Ultrasound Parameters of Drug Eluting Stent Efficacy from Taxus IV, V, and VI. Am J Cardiol, 2007: 100:621-6
QCA Measurements CDF Curves
In-Stent
Percent Diameter Stenosis
Post
Follow-up
Pre
Minimal Luminal Diameter
Pre
Follow-up Post
CDF: Cumulative Distribution Function
IVUS Sub-Group
Paired Analysis
Post9 mo Follow-up
Paired IVUS
procedure
N=25 lesions
N=25 lesions
Stent Length (mm)
18.02 ± 4.12
17.50 ± 3.73
Stent Area (mm2)
8.37 ± 3.08
8.44 ± 3.13
Lumen Area (mm2)
8.36 ± 3.19
8.03 ± 3.14
Plaque Area (mm2)
6.62 ± 2.77
7.29 ± 2.84
EEM Area (mm2)
14.98 ± 5.16
15.31 ± 5.31
MLA (mm2)
6.81 ± 2.58
6.52 ± 2.65
Stent Volume (mm3)
155.19 ± 82.27 151.1 ± 79.54
Lumen Volume (mm3)
154.79 ± 83.13 143.67 ± 78.57
Plaque Volume (mm3)
121.52 ± 57.14 129.42 ± 59.63
EEM Volume (mm3)
276.3 ± 129.3 273.09 ± 128.96
Intimal Hyperplasia Volume (mm3)
7.43 ± 8.04
Neointimal Volume Index
0.41 ± 0.43
In-Stent Neointimal Volume Obstruction (%)
5.39 ± 5.28
P
0.36
0.63
0.07
<0.01
0.15
0.18
0.53
0.08
0.14
0.75
IVUS Sub-Group
QCA 9 Months
9 months (n=26) Qualitative Measurements
Reference vessel diameter (mm)
In-stent
MLD (mm)
Diameter stenosis (%)
Late lumen loss (mm)
Binary restenosis (%)
In-segment
Length (mm)
MLD (mm)
Diameter stenosis (%)
Late lumen loss (mm)
Binary restenosis (%)
Mean ± SD, (median)
2.54 ± 0.46 (2.53)
2.32 ± 0.57 (2.33)
8.3 ± 17.42 (7.36)
0.23 ± 0.33 (0.19)
0 % (0/26)
25.19 ± 4.41 (25.61)
1.98 ± 0.49 (1.89)
21.87 ± 12.87 (21.26)
0.25 ± 0.34 (0.26)
0% (0/26)
Clinical Outcomes* to 12 Months
N = 72
1 Mo
3 Mo
4 Mo
6 Mo
9 Mo
12 Mo
MACE
4 (5.56%)
4 (5.56%)
4 (5.56%)
5 (6.97%)
6 (8.40%)
10 (14.12%)
Death
1 (1.41%)
1 (1.41%)
1 (1.41%)
3 (4.23%)
3 (4.23%)
4 (5.63%)
0
0
0
1 (1.43%)
1 (1.43%)
1 (1.43%)
4 (5.56%)
4 (5.56%)
4 (5.56%)
4 (5.56%)
4 (5.56%)
4 (5.56%)
ci TLR
0
0
0
0
1 (1.47%)
5 (7.35%)
Ci TVR
0
0
0
0
1 (1.47%)
5 (7.35%)
Def. ST
0
0
0
0
0
0
1 (1.41%)
1 (1.41%)
1 (1.41%)
3 (4.23%)
4 (5.63%)
9 (12.68%)
Card. Death
MI
Death or TVR
*Percent values are Kaplan-Meier estimates
DAPT Compliance
DAPT
N = 72
Month 01 Month 03 Month 04 Month 06 Month 09 Month 12
69
67
70
69
67
67
66
(95.7%)
67 (97.1
%)
65
(97.0%)
48
(71.6%)
69
(98.6%)
12
(17.1%)
67
(97.1%)
67 (100%)
65
(97.0%)
4 (5.8%)
5 (7.5%)
6 (9.0%)
Prasugrel (%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
0 (0%)
Ticagrelor (%)
1 (1.5%)
0 (0%)
1 (1.4%)
0 (0%)
0 (0%)
5 (7.5%)
DAPT
65
(94.2 %)
46
(68.7%)
12
(17.1%)
4 (5.8%)
5 (7.5%)
9 (13.4%)
Bleeding
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
0 (0.0%)
Aspirin (%)
Clopidogrel (%)
Conclusions
•Despite a more complex patient profile than usual for early safety
and feasibility studies, treatment with the BioFreedom™ DCS was
safe with a low incidence of clinical events up to 12 months.
•The BioFreedom™ stent also showed good anti-restenotic efficacy
as measured by QCA and IVUS at 9 months.
•The DAPT cessation at 3 months was not associated with any
incidence of definite or probable stent thrombosis, indeed, no
def/prob ST was noted up to 1 year of follow-up.
•BioFreedom™ may offer a promising alternative to traditional DES
for patients in need of shorter DAPT regimens.
22
Thank You for Your Attention
Death, MI and Def ST 12 months
* 180 days
MACE, TVR and TLR 12 months
* 180 days
MACE, TVR and TLR 12 months
14.00%
12.00%
10.00%
8.00%
DM
6.00%
NoDM
4.00%
2.00%
0.00%
MACE
* 180 days
TVR
TLR
ST, Def