1. New Generation Resolute Integrity Drug-Eluting Stent Superior to Benchmark Xience Drug-Eluting Stent: Primary Endpoint Results from the PROPEL Study – a Historical Controlled, Prospective, Multicenter, Clinical Study of All-Comers Design
Masato Nakamura, MD1, Satoru Otsuji, MD2, Yoshihisa Nakagawa, MD3, Yuji Oikawa, MD4, Nobuo Shiode, MD5, Masatoshi Miyahara, MD6, Gaku Nakazawa, MD7 and Hiroyoshi Yokoi, MD8, on behalf of the PROPEL Study Investigators
1 Toho University Medical Center, Ohashi Hospital, Tokyo, Japan; 2 Higashi Takarazuka Satoh Hospital, Hyogo, Japan; 3 Tenri Hospital, Nara, Japan; 4 The Cardiovascular Institute, Tokyo, Japan; 5 Tsuchiya General Hospital, Hiroshima, Japan; 6 Mie Heart Center, Mie, Japan; 7 Tokai University Hospital, Kanagawa, Japan; 8 Fukuoka Sanno Hospital, Fukuoka, Japan
ACC 2016

2. Author Disclosures
Dr. Nakamura is a consultant for Terumo Corporation, and lectures for Boston Scientific, Abbott Vascular, Terumo Corporation, and Medtronic Japan. Dr. Nakazawa is a consultant for Abbott Vascular Japan, Terumo Corporation, Japan Medical Device Engineering, and St. Jude Medical, and receives research grants from Abbott Vascular, Terumo Corporation, Boston Scientific, Daiichi Sankyo, and Japan Medical Device Engineering. All other authors have nothing to disclose.

3. Background
The Resolute Integrity™ zotarolimus-eluting stent (Medtronic) utilizes the Continuous Sinusoidal Technology, which forms the stent out of a single wire and improves deliverability.
The PROPEL study is the first large, real world study to assess the safety, efficacy and deliverability of Resolute Integrity compared with a historical control, Xience V™ Everolimus-eluting stent (Abbott Laboratories).

4. Objectives
To assess the safety, efficacy and deliverability of the Resolute Integrity stent in a large real-world Japanese patient population with coronary artery disease implanted with the Resolute Integrity device.
Hypothesis: non-inferiority followed by superiority testing of Resolute Integrity for TLF in patients with only clinical follow-up at 12 months, compared to the Xience arm from R-AC trial as historical control.

5. PROPEL Study Design
Prospective, Single Arm, Open Label, Multi-center Study
All Comer Population:
All patients with coronary artery disease
eligible for DES implantation
Vessel diameter 2.5 – 3.5 mm
Resolute Integrity™ ZES
N = 1204
(Clinical f/u cohort N=905)
Historical control
Xience V™ EES
(R-AC)1
76 sites in Japan
Clinical follow-up
30d
9mo
10mo
12mo
Angio follow-up
Angio f/u cohort
only (N=299)
Primary Endpoint: Target Lesion Failure (TLF) at 12 months
Key Secondary endpoints:
Incidence of TLF, TVF, MACE, major bleeding, ARC def/prob ST at 1, 9 and 12 months
QCA outcomes at 10 months (angio f/u cohort)
Drug Therapy: ASA and clopidogrel/ticlopidine ≥ 6mo (per guidelines)
1 Serruys PW, et al., N Engl J Med. 2010;363(2):136-46

6. Patient Disposition PROPEL Xience arm RESOLUTE All Comers*
All patients treated with Resolute Integrity
N=1204 pts
Xience arm RESOLUTE All Comers*
N=1152 pts
Angio f/u cohort
N=299 pts
Clinical f/u cohort
N=905 pts
QCA follow-up at 10 months
n=200 pts (67%)
Primary endpoint, non-inferiority of 12-mo TLF
Clinical follow-up at 12 months
n=255 pts (85%)
Clinical follow-up at 12 months
n=800 pts (88%)
Clinical follow-up at 12 months
n=1126 pts (98%)
* Angiographic follow-up occurred at 13 months in R-AC; therefore, all patients had only clinical follow-up at 12 months.

7. Baseline Patient Characteristics
Variable, %
All patients
(N=1204)
Clinical f/u cohort
(N=905)
Age (yr)
69.7 ± 9.7
69.7 ± 9.6
Male
77.7
77.6
Diabetes mellitus
41.3
41.7
IDDM
6.5
7.6
Hypertension
81.8
81.1
Hyperlipidemia
75.8
75.7
Current smoker
19.9
20.0
Prior MI
22.1
21.1
Prior PCI
41.2
39.7
Prior CABG
4.1
3.8
Cardiac status:
Stable angina
45.9
46.0
Unstable angina
16.1
16.8
Acute myocardial infarction (<72h)
10.3
10.7
STEMI
8.2
8.7
Complex patients1
60.5
59.3
1 Complex patient definition: bifurcation, bypass grafts, ISR, AMI <72 hr, LVEF <30%, unprotected LM, >2 vessels stented, renal insufficiency or failure (creatinine >140 µmol/L), lesion length >27 mm, >1 lesion per vessel, lesion with thrombus or TO (pre-procedure TIMI = 0).

8. Baseline Lesion Characteristics
Variable, % or mean ± SD
All patients
(N=1204,
N=1522 lesions)
Clinical f/u cohort
(N=905;
N=1129 lesions)
Vessel location per lesion
LAD
42.8
43.3
LCX
22.1
21.5
RCA
32.6
Left Main
2.4
2.3
RVD (mm)
2.68 ± 0.48
2.65 ± 0.47
Lesion length (mm)
16.62 ± 10.02
16.12 ± 9.73
MLD (mm)
0.93 ± 0.48
0.91 ± 0.47
% Diameter stenosis
65.22 ± 16.88
65.62 ± 16.65
Type B2/C lesion
79.5
78.4
SYNTAX score
11.1 ± 8.0
11.2 ± 8.0
Patients with bifurcation lesion
25.8
25.7
Patients with in-stent restenosis
7.9
8.4
Patients with chronic total occlusion
5.3
4.5
Patients with multi-vessel treatment
13.1
12.9
Patients with small vessel (<2.5mmm RVD)
41.9
44.7

9. Effectiveness Measures
All patients
(N=1204 patients,
N=1522 lesions)
Clinical f/u cohort
(N=905 patients,
N=1129 lesions)
Lesion success (%)1
100.0
Device success (%)2
97.9
97.7
Procedure success (%)3
99.3
99.1
1 The attainment of <50% residual stenosis of the target lesion using any percutaneous method.
2 The attainment of <50% residual stenosis of the target lesion using only the RI-ZES.
3 The attainment of <50% residual stenosis of the target lesion and no in-hospital MACE.

10. Dual Anti-Platelet Therapy
Patients receiving DAPT (%)
All patients
(N=1204)
30 days
97.2
6 months
95.4
9 months
85.1
12 months
78.7
DAPT was defined as aspirin and either clopidogrel, ticlopidine or prasugrel

11. Angiographic Cohort Outcomes
QCA Follow-up at 10 Months
Late loss (mm, mean ± SD)
Angiographic f/u cohort
(n=254 lesions)
In-segment
0.16 ± 0.37
In-stent
0.26 ± 0.39

12. Primary Endpoint Target Lesion Failure at 12 Months
PNon-inferiority <0.001
PSuperiority* <0.001
Δ = - 4.2%
Target Lesion Failure (%)
Resolute Integrity
PROPEL Clinical Cohort
(n=800)
Xience
RESOLUTE All-Comers
(n=1142)
Non-Inferiority Endpoint Met
Superiority Demonstrated
P-values were pre-specified to be adjusted by propensity score for differences in lesion length, pre-procedure RVD, age, male gender, diabetes mellitus, prior myocardial infarction, and SYNTAX score.
*Pre-specified superiority analysis if non-inferiority test was met

13. Clinical Outcomes at 12 Months
All Patients
Events (%)
TLF (target lesion failure) is defined as cardiac death, target vessel MI and clinically driven TLR. TLR is clinically driven.
Major bleeding is defined according to the REPLACE-2 definition

14. Clinical Outcomes at 12 Months%
PROPEL
All patients
(n=1055)
Clinical-only cohort
(n=800)
Xience arm in RESOLUTE
All-Comers
(n=1142)
Death (all)
1.6
1.9
2.7
Cardiac
0.8
1.0
1.7
Target vessel MI
0.2
0.1
4.2
Cardiac death or target vessel MI
0.9
1.1
5.5
ARC Definite/Probable ST
0.3
0.7
Early (0-30 days)
0.5
Late ( days)
0.0
Clinically-driven TLR
3.7
3.3
3.4
Clinically-driven TVR
5.1
4.1
4.8
TLF (cardiac death, TV-MI, TLR)
4.5
4.3
8.5
TVF (cardiac death, TV-MI, TVR)
6.0
9.7
MACE (death, MI, TLR, emCABG)
5.3
9.8

15. Target Lesion Failure (%)
Subgroup Outcomes
Target Lesion Failures at 12 Months
Target Lesion Failure (%)
TLF (target lesion failure) is defined as cardiac death, target vessel MI and clinically driven TLR.

16. Acute Deliverability Assessment
Resolute Integrity vs. Other DES
N=1204

17. Conclusions
This is the first study to demonstrate superiority of a new generation DES (Resolute Integrity) to the benchmark Xience DES in a historical comparison (TLF 4.3% vs 8.5%, P<0.001).
Procedural outcomes were excellent with lesion and procedure success rates at 100% and 99%, respectively.
At 12 months, the incidence of clinical events was low in all patients and also across various subgroups.
The Resolute Integrity stent with the Continuous Sinusoidal Technology had improved deliverability and excellent clinical outcomes .