1. A randomized control trial comparing two second generation drug-eluting stents on the degree of early stent healing and late neointima progression using longitudinal sequential OCT follow-ups:
The OCT-ORION Study
LEE WL Stephen (1), TAM CC Frankie (1), CHAN KW Kelvin (1), KONG SL (1), LAM SC Simon (1), WONG KL Michael (1), WONG YT Anthony (1), YUNG Arthur (1), SHEA P Catherine (1), LAM YM (1), ZHANG LW (1), WU K Karl (1), MINTZ Gary (2), MAEHARA Akiko (2)
Queen Mary Hospital, The University of Hong Kong, Hong Kong, HONG KONG
Cardiovascular Research Foundation, New York, UNITED STATES (QCA & OCT Core Laboratory)

2. Potential conflicts of interest
Speaker's name: Stephen W. L. Lee
 I do not have any potential conflict of interest
All stents were provided as free investigational study devices by Biosensors International Limited (BioMatrix Stents) and Medtronic Inc. (Resolute Integrity Stents).

3. The OCT-ORION Study Study Aim Methodology
Drug Eluting Stents (DES) are proven to reduce restenosis, at the expenses of prolonged dual anti-platelet therapy (DAPT) and adverse development of “late stent failure”.
Poor stent healing and late stent failure (thrombosis, accelerated neo-atherosclerosis & late catch-up) have been reported to be associated with polymer hypersensitivity and/or drug toxicity after DES implantation.
A proof of concept that a protocol could be designed to identify differences between different stent platforms using a much smaller sample size.
Methodology
To evaluate the differences and outcomes of two different 2nd generation DESs (BioMatrix NeoFlex vs. Resolute Integrity) by:-
(a) longitudinal sequential OCT assessments - quantification of the early (2 to 6 months) stent strut coverage (healing) and mid-term (9 months) neo-intimal progression and OCT metrics;
(b) to minimise any confounding factors, each patient would be receiving both of the study stents in the same index PCI procedure (must be 2 to 3-vessel disease).

4. BioLinx “durable” “hydrophilic” polymer (very low inflammatory score)
Postulations:- (a) BioMatrix better early (2 to 6 months) healing / coverage
(b) Resolute-Integrity better 9 months neointimal suppression
Biolimus BA9
15.6 g/ mm
45% by 30 days
BioMatrix
PLA:BA9 = 50:50
BioLinx “durable” “hydrophilic” polymer
(very low inflammatory score)
Resolute Integrity
Zotarolimus 85% eluted first 60 days
Extended 180 days (6 months) drug elution

5. Design & Methods Study Flow Chart Study Status
Prospective, randomised, single center
60 patients with > 2-vessel disease
5 monthly group randomly assigned to 2-6M in 1:1:1:1:1 ratio; and randomly receiving BX or RI stent in each vessel
Real world, all-comers except STEMI
3 longitudinal sequential OCT assessments
* NIT, NIA, NIV denote neointimal thickness, area & volume by OCT.
ᵻ Infarct-related artery would be documented as far as possible.
Study Flow Chart
RI = Resolute Integrity Stent
BX = BioMatrix NeoFlex Stent
Study Status
Study completed ; 100% OCT FU rate.
QCA & OCT analyses in a blinded fashion (Cardiovascular Research Foundation, NY, USA).
Mean Clinical FU to date = 730 days.

6. Patient demographics and procedural characteristics
OCT-ORION Study
Patient demographics and procedural characteristics
Total
2 months
3 months
4 months
5 months
6 months
Number of patients 60 12 11 13
Mean Age (years)
62.5 ± 11.9
60.5 ± 10.9
64.6 ± 15.6
66.5 ± 9.4
59.6 ± 11.6
61.5 ± 11.4
Male (% within group)
50 (83.3%)
10 (83.3%)
9 (81.8%)
11 (84.6%)
Diabetes Mellitus
55%
58.3%
54.6%
50%
53.9%
Hypertension
46 (76.7%)
8 (66.7%)
9 (75%)
12 (92.3%)
Hyperlipidemia
37 (61.7%)
6 (50%)
6 (54.6%)
8 (61.5%)
History of Smoking
29 (48.3%)
5 (41.7%)
6 (50%)
6 (46.2%)
Prior Myocardial Infarction
16 (26.7%)
3 (25%)
4 (33.3%)
1 (9.1%)
4 (30.8%)
Prior Percutaneous Coronary Intervention
8 (13.3%)
2 (16.7%)
1 (8.3%)
0 (0%)
2 (15.4%)
Clinical Presentation at Index Procedure
Stable angina
52 (86.7%)
12 (100%)
8 (72.7%)
NSTEMI or Unstable angina
3 (27.3%)
1 (7.7%)
Number of Lesions
120
24 (19.7%)
24 (20%)
22 (18.3%)
26 (21.7%)
LAD
50 (41.7%)
9 (37.5%)
11 (45.8%)
10 (45.5%)
10 (41.7%)
10 (38.5%)
LCx
41 (34.2%)
5 (22.7%)
8 (30.8%)
RCA
29 (24.2%)
6 (25%)
4 (16.7%)
7 (31.8%)
Number of Stents Implanted
144 30 27 28 24 35
Per Lesion Treated
1.2 ± 0.4
1.3 ± 0.4
1.1 ± 0.3
1.3 ± 0.5
1 ± 0
1.3 ± 0.6
Resolute Integrity (total number) 73 16 19
(mean per lesion)
1.2 ± 0.5
1.1 ±0.3
1.5 ± 0.5
1 ± 0
1.5 ± 0.7
BioMatrix (total number) 71 17 14
1.4 ± 0.5
Mean Stent Length (mm)
Resolute Integrity
27.1 ± 8.2
24.4 ± 6.0
26.6 ± 7.4
30.4 ± 10.4
24.1 ± 6.8
30.1 ± 9.0
BioMatrix
27.5 ± 8.5
30 ± 11.7
27.2 ± 6.8
27.9 ± 7.9
23 ± 6.1
29.2 ± 8.4
Mean Stent Diameter (mm)
Resolute Integrity (mm)
2.79 ± 0.32
2.88 ± 0.27
2.71 ± 0.26
2.90 ± 0.27
2.83 ± 0.44
2.66 ± 0.30
BioMatrix (mm)
2.83 ± 0.37
3.02 ± 0.53
2.67 ± 0.20
2.86 ± 0.30
2.88 ± 0.33
2.75 ± 0.34

7. Frame by frame analysis
OCT Methodology
Frame by frame analysis

8. DM Subset Overall 2-6M % Strut Coverage
Early 2-5M Results
2M to 6M percentage strut coverage
* Data failed assumption for Normality per the Shapiro-Wilks Test; p-value and IQR derived from Wilcoxon Signed Ranks Test
* An ANCOVA with random effects for subjects was used to test equality of slopes. The p-value was taken from the Type III SS for the interaction between stent type and log time.
DM Subset Overall 2-6M % Strut Coverage BX RI
Median 95.5% vs. 97.5%
p=0.0016
As shown in the Bar Chart between group comparison, RI had significantly higher “early” (2 to 6M) strut coverages than BX in all 5 groups.
Longitudinally, as shown in the Percentage Strut Coverage Curve over time, RI had a better healing profile than BX in early months, suggesting the use of a well-tested durable polymer may not be inferior to the use of a biodegradable polymer.
RI also had significantly better percentage strut coverage in the DM sub-group.

9. RI had significantly better coverage than BX at 9 months
Primary End-point: % Strut Coverage at 9 months (Median [Q1-Q3])
RI = 99.7% [99.1, 100] versus BX = 99.6% [96.8, 99.9], p=0.0009
RI had significantly better coverage than BX at 9 months
Results at 9 Months RI BX
Also much more scattering (incomplete coverage) was observed with BioMatrix even at 9M.
QCA: In this group of patients with very advanced disease (2 to 3 vessels), both stents showed comparable efficacy of neointimal suppression at mid-term of 9 months ( ≤5% angiographic binary restenosis ).
Clinical outcomes: only 1 patient required revascularization (RI arm); no MI or ARC defined stent thrombosis was observed in either group. All events and results were adjudicated.

10. Longitudinal Sequential OCT Metrics from 2M to 9M
Results at 9 Months
Longitudinal Sequential OCT Metrics from 2M to 9M
* Excessive blood artifact, OCT could not be confidently analyzed in 1 case with BX stent at 9M

11. Summary of Longitudinal Sequential OCT Metrics from 2M to 9M
Results at 9 Months
Summary of Longitudinal Sequential OCT Metrics from 2M to 9M BX RI
Median Number of OCT frames Analyzed
Median Number of OCT struts Analyzed
Median
Neointimal Thickness (NIT, mm)
Median Neointimal Area (NIA, mm2)
Neointimal Volume (NIV, mm3)
Median % NIV
(%)
2 Months
(n=12)
BX: 157
RI: 141
BX: 1158
RI: 1446
0.029 vs
P = 0.98
0.232 vs
P = 0.99
7.37 vs. 6.74
P = 0.61
3.35 vs. 3.47
P = 0.84
3 Months
BX: 145
RI: 151
BX: 988
RI: 1438
0.028 vs
P = 0.03
0.186 vs
P = 0.25
4.33 vs. 6.26
P = 0.35
3.25 vs. 3.67
4 Months (n=11)
BX: 169
RI: 173
BX: 1093
RI: 1765
0.044 vs
P = 0.20
0.305 vs
P = 0.14
8.66 vs
P = 0.15
4.0 vs. 6.32
P = 0.16
5 Months (n=12)
BX: 132
RI: 133
BX: 903
RI: 1411
0054. vs
P = 0.02
0.416 vs
P = 0.01
9.24 vs
5.93 vs. 9.31
P = 0.18
6 Months
(n=13)
BX: 172
BX: 1161
RI: 1832
0.051 vs
P = 0.002
0.276 vs
6.12 vs
4.57 vs. 7.82
P = 0.004
9 Months
(BX: n=59* RI: n=60)
BX: 150
RI: 147
BX: 1038
RI: 1518
0.073 vs
P < 0.001
0.496 vs
13.50 vs
8.07 vs
* Due to excessive blood artifact, OCT could not be confidently analyzed in 1 case with BX stent at 9M
Both BX and RI exhibited efficacy as a DES in neointimal suppression as shown by minimal NIT, NIA and NIV at 9 months by OCT.
BX showed significantly lower NIT, NIA and NIV at the expenses of lesser healing (less % coverage and more scattering) at 9 months.
Morphologically, RI also showed better maturation with more homogenous neointima by 9 months.

12. Study Summaries OCT-ORION Study Thank you
Longitudinal sequential OCT assessments could provide maximal information on the safety & efficacy, in-vivo biological behavior, & subsequent neointimal changes of any DES, benefiting better patient treatment.
Simultaneously comparing 2 stents in each individual patient could minimize any confounding factors, providing better data information with less contamination on the benefits of various stents.
2 second generation DES were compared:- one with stable durable polymer & zotarolimus (Resolute Integrity); the other with biodegradable polymer & Biolimus A9 (BioMatrix).
Postulations:- (a) BioMatrix better early (2 to 6 months) healing / coverage,
(b) Resolute-Integrity better 9 months neointimal suppression.
Despite the postulation, RI (Zotarolimus with a durable polymer) exhibited non-inferior early healing and less incomplete strut coverage than BX (BA9 with a biodegradable polymer) at 9 months, with more mature neointima but thicker NIT, NIA & NIV by OCT.
Establishment of early healing profile (early strut healing & coverage) could guide optimal duration of DAPT for each DES, balancing stent thrombosis versus bleeding risk.
Safety and efficacy: Both stents showed comparable neointimal suppression. Restenosis were similar to other DES reported. No stent thrombosis nor MI was recorded so far. Study Limitations:- need longer term clinical results for correlations.
This protocol could represent a novel protocol and may be surrogated for future stent studies (comparing both stent healing and neointimal progression) so that much smaller sample size may be required to achieve conclusive results in a much shorter time.
Thank you