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09

Overview Of Abluminus DES+

Robust And Comprehensive Clinical Programs

en-ABL 1 Study

en-ABL e-registry

en-ABL LM Study

DEDICATE Registry

ABILITY RCT

ABILITY Global

Abbreviations

Abluminus DES+ In Diabetes MellitusAbluminus DES+ In AMI

0102

We, Concept Medical would like to extend our gratification to all individuals who have helped and inspired us throughout the conduct of all our registries. It is our privilege to express our heartfelt thanks to Dr. Sameer Dani, Chief Investigator of en-ABL e and en-ABL 1 Registry for his continued support. We are also honoured to take this opportunity to forward our gratitude and appreciate Dr. Paolo Vicinelli, Principal Investigator of en-ABL LM STUDY.

We are also glad to acknowledge Dr. Luca Testa, Principal investigator of DEDICATE REGISTRY and Dr. Azeem Latib, Principal Investigator ABILITY RCT Study for their constant source of encouragement and succour, which provided impetus and paved the way for the successful commencement of this clinical study. The current work would not have been possible without the expertise and guidance from all the scholarly investigators during these studies. In addition, they were always accessible and willing to help us with our research. We gratefully recognize and appreciate all the investigators for their zeal and constant encouragement throughout the course of these studies.

Finally, we must express our very profound gratitude to the whole team for providing the unfailing support and continuous invigoration throughout the process of research and writing this booklet.The credit goes to all our team and the keen investigators who have been a part of this journey.This accomplishment would not have been possible without them.

Thank you

Acknowledgement

For Concept Medical

MANISH DOSHI

Managing Director

0202

Overview of Abluminus DES+ABLUMINUS DES+ (Designed to treat Diabetic Patients)Abluminus DES+ is a Cobalt Chromium Stent System specially designed for diabetic patients and CE approved for diabetic and AMI Indication. It is an abluminally coated Sirolimus Drug Eluting Stent. The drug is coated on both the stent and the exposed parts of the balloon.

DIABETES MELLITUS: AN UNMET CLINICAL NEEDDiabetes mellitus (DM) is a major public health problem.415 million people worldwide, or one in eleven adults are estimated to have DM. If the current trend in diabetes prevalence continues, by 2040 some 642 million people, or one adult in ten, will have diabetes [1].

Patients with DM are more a�ected by Coronary Artery Disease (CAD) and when treated by Percutaneous Coronary Interven-tion (PCI) with stent implantation they remain at higher risk for in-stent restenosis and adverse cardiovascular events [2-4]. The diabetic patient presents a well-known pattern of CAD – extensive atherosclerosis, a greater number of significant stenosis, longer lesions and more di�use and distal disease [5]. The presence of DM (particularly insulin-treated DM) has been a consis-tent, independent predictor of in-stent restenosis [6].

Although second-generation DES seem to provide superior safety and e�cacy when compared with first-generation DES, late adverse events remain a problem, presumably because of a persistent inflammatory response in the arterial wall. It has been speculated that the use of stents with biodegradable polymers or without a polymer may avoid late events caused by the chronic inflammation related to its presence [7].

Multiple factors lead to diabetic patients having an impaired endothelial function. These include hyperglycaemia, excess of free fatty acids and insulin resistance. The increased production of tissue factor and plasminogen activator inhibitor-1 create a pro-thrombotic environment that, together with the increased ability of platelets to aggregate, leads to an increased propensi-ty for thrombotic complications in diabetic patients. Thus, it is not unexpected that DM in combination with premature discontinuation of antiplatelet therapy; bifurcation lesions, low ejection fraction and renal failure has been identified as an independent predictor of late thrombotic events after DES implantation [8].

Patients with DM represent 20-30% of all PCI performed. Furthermore, they represent a very complex subgroup of patients since their coronary artery disease is more extensive. Over the years, stent technology has been developed and clinical outcomes have improved mainly in non-diabetic patients. In diabetic patients we continue to struggle to o�er them the best results with PCI. In addition, diabetic patients with multi-vessel disease still benefit most with coronary artery bypass graft surgery. With this, Abluminus DES is designed to treat diabetic patients with envisolution technology.

Envisolution TechnologyAN ENHANCED DRUG DELIVERY TECHNOLOGY WITH HOMOGENEOUS DRUG COATING

ABLUMINAL COATING Facilitate mono directional drug release and less systemic exposure of drug leading to faster re-endothelialisation

FUSION COATINGCoating on the stent and exposed parts of the balloon facilitate homogenous drug delivery which address di�used proliferative disease and focal restenosis

EDGE COATING The additional 0.5mm coating on the edge of the balloon which addresses the edge restenosis

BIODEGRADABLE FILM

The formation of circular film with biodegradable polymer facilitate maximum drug delivery in blood wet conditions

Abluminus DES+, addresses the nature of the diabetic lesion in the patients and properly provides thedesired treatment.

03

Study Name Type of Study Target Patients Country Status

en-ABL 1 Study

en-ABL e-Registry

en-ABL LM Study

DEDICATE Registry

ABILITY RCT

Prospective, Single centre, Non- randomized clinical trial

Multi-center, Prospective, All-comers registry

Retrospective,All-comers study

Prospective, Multi-center, Spontaneous clinical registry

Multi-centre, Single-blinded, Randomized, Investigator-initiated pilot clinical study

40 Patients

2,500 Patients

24 patients

5,000 Patients

165 Patients

INDIA

INDIA

ITALY

GLOBAL

ITALY

36 months data available

Enrolment completed, follow-up ongoing

36 months data available

Enroling

Enroling

Robust And Comprehensive Clinical Programs

Study Name Type of Study Target Patients Country

ABILITY GLOBAL Prospective, Multicentre, Multinational, Randomized, Open label, 2-arm parallel groups

3, 000 Patients GLOBAL

UPCOMING CLINICAL TRIALS

More than 12,000 patients Planned and Enroled

04

en-ABL 1 STUDY

INTRODUCTION AND OBJECTIVES

The Abluminus DES+, a novel Abluminal surface coating on stent and exposed parts of balloon in pre-crimped condition with Sirolimus. We sought to investigate the performance and e�cacy of this novel DES technology in patients treated in daily clinical practice.

METHOD

The en-ABL 1 FIM trial was prospective, single-center, non-randomized, single-arm, first-in human evaluation of safety, feasibility and performance of ABLUMINUS DES+. Inclusion criteria were without limitation to number of lesions, vessels and lesion length as real-world population. Clinical follow-up was performed at 1, 6, 12, 24 and 36 months. All patients were assigned for angiographic re-evaluation at 6 months, and the primary endpoint was in-stent Late Lumen Loss (LLL), as determined by independent Quantitative Coronary Angiography (QCA) analysis.

RESULTS

A total 40 patients (56 lesions) were enrolled between March 2012 and August 2012. Mean age was 54.35±10.51 years, 17(42.5%) were diabetics, 25(62.5%) were hypertension and 11(47.5) had a previous myocardial infraction (MI). Baseline median [25%, 75% interquartile range] lesion length, reference vessel diameter, MLD and % diameter stenosis were respectively 14.9[10.4,23.0] mm, 2.33[2.09,2.75] mm, 0.75 [0.45,0.98] mm and 67.4 [61.2,78.8]. Average stent per patient, stent length, stent diameter and inflation time were 1.40, 27.35 mm, 2.87 mm and 28 seconds respectively. At 6-months angiographic follow-up (39/40), median in-stent LLL was 0.14 [0.06,0.29] and of total lesions 3.7% binary restenosis was observed. Clinical follow-up MACE (composite of death, MI and target lesion revascularization) was 2.5% at 12 months follow-up. There was no stent thrombosis (ST) event recorded up to 12 months follow-up. There was one cardiac death and no ST reported through 36 month follow-up.

CONCLUSION

A novel abluminal coated Sirolimus eluting stent Abluminus DES+ in en-ABL 1 first-in-human study demonstrated excellent performance (100% procedural success), e�cacy with optimum LLL at 7 months despite complex lesions and small vessels and low MACE at 36 months with no event of stent thrombosis.

05

DiabetesN= 859

en-ABL e-RegistryN=2,500

en-ABL e-Registry

Principal Investigator:

Dr. Sameer Dani¹

Dr. Devang Desai ²; Dr. Nirav Bhalani ³, Dr. Arvind Sharma ³, Dr. Chirag Sheth ³, Dr. PrathapKumar N. Pillai ⁴, Dr. Jitendra Singh ⁵, Dr. Rutvik Trivedi ⁶, Dr. Kaushal Pujara ⁶, Dr. Mukesh Goyal ⁷, Dr. Apurva vasavada ⁸, Dr. Rashmit Pandya¹, Dr. Pritesh Parekh ⁹

1. Life care Institute of Medical Sciences and Research and Apollo Hospitals, Ahmedabad, India.2. Mahavir Hospitals, Surat, India.3. Rhythm Heart Institute, Baroda, India.4. Meditrina Hospital, Trivandrum, India.5. Lotus Super Specialties Hospital, Agra, India.6. Zydus Hospitals and Healthcare Research Pvt Ltd, Anand, India. 7. Upadhyay Hospital, Agra, India.8. Tristar Hospital, Surat, India.9. Care Hospitals, Surat, India.

ObjectiveTo evaluate the safety and e�cacy of the Abluminus DES+ in an all-comers population with minimal exclusion criteria.

Study DesignMulticenter, prospective, all-comers clinical registry performed in 31 centers in India. Patients are followed-up with ambulatory visits or telephone contact at 1 month, 9 months, 1 year and yearly afterwards up to 5 years after the index procedure.

ENDPOINTS

Primary EndpointMajor Adverse Cardiac Events (MACE) is composite of Cardiac Death, Target Vessel MI (TV-MI), Target Lesion/ Vessel Revascularization (TLR/ TVR) at 1 year follow-up.

.Secondary EndpointStent Thrombosis (ST) according to the ARC definition calculated at any time point; MACE assessed up to 2 years.

OVERVIEW OF SUBGROUPS FROM en-ABL e-REGISTRY

AMI Subgroup Small VesselSubgroup

Long LesionSubgroupN= 999

N= 1,253 N= 1,479

06

RESULTS – OVERALL PATIENTS

Patients Fow-chart

2,500 Patients 2,495 (99.8%) Patients completed 1 year follow-up

2,246 (89.8%) Patients completed 2 years follow-up till April 2019

5 Patients lost to follow-up

Complex Real-world Patients

Overall Patients, N-2,500

Age, Years ± SDMale, %Female, %

57.0 ± 12.678.921.1

Previous CV History, %

MIPCICABG

11.85.92.0

Cardiovascular Risk Factors, %

HypertensionDiabetes Mellitus

42.234.4

Clinical Presentation, %

Stable AnginaInducible IschemiaACS STEMI NSTEMI Unstable Angina

6.227.066.842.84.219.8

Extent of Coronary Artery Disease, %

1 -Vessel2- Vessel3-Vessel4-Vessel

83.214.81.90.04

Overall patientsNo. of lesions=2,969No. of devices=3,287

No. of Treated Lesion per patientNo. of Stents per patient

1.21.3

Target Vessel, %

Left Anterior DescendingLeft CircumflexRight Coronary ArteryRamusLeft MainBypass Graft

48.921.227.31.40.80.4

Lesion Details, %

Small vessel (≤2.75mm)Long lesions (≥28 mm)

47.255.2

Procedural details, % Pre-DilatationThrombus AspirationPost-DilatationDevice SuccessProcedure Success

68.91.843.2100.099.2

Baseline Characteristics

Procedural details, %

Procedural details, % Mean Stent DiameterMean Stent Length

2.9 ± 0.426.8 ± 8.8

Device Characteristics (mm ± SD)

Patients Underwent Follow-up, N

MACE, %Cardiac Death, %TV-MI, %TLR/TVR, %ST, %

2.81.00.41.40.6

2,495 2,246

3.01.10.41.50.6

1 year 2 years

Cumulative Clinical Outcomes Up To 2 years

07

Time-to-event curve for the MACE and ST

Time-to-event analysis for composite endpoint MACE, individual component of MACE and ST at 1 year and 2 years are presented in following Figure. The event rates presented here were calculated by Kaplan–Meier methodology.

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0 2 4 6 8 10 12

MACE: 2.8%

TLR/TVR: 1.4%

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Months After Index PCI

1.00

4.00

2.00

Pts at risk: 2,495 2,454 2,427

Cardiac Death: 1.0%

TV-MI: 0.4%

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3.00

0.00

0 2 4 6 8 10 12

Total ST: 0.6%

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Months After Index PCI

1.00

4.00

2.00

Pts at risk: 2,495 2,481 2,481

Definite ST: 0.4%

Probable ST: 0.2%

MACE at 1 year

ST at 1 year

08

MACE at 2 years

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3.00

0.00

0 5 10 15 20 25

MACE: 3.0%

TLR/TVR: 1.5%

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Months After Index PCI

1.00

4.00

2.00

Pts at risk: 2,246 2,203 2,176

Cardiac Death: 1.1%

TV-MI: 0.4%

5.00

3.00

0.00

0 5 10 15 20 25

Total ST: 0.6%

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Months After Index PCI

1.00

4.00

2.00

Pts at risk: 2,246 2,232 2,232

Definite ST: 0.4% Probable ST: 0.2%

ST at 2 years

09

Parameters, N (%)

Diabetes (N= 859)

No diabetes (N= 1,641)

Hypertension (N= 1,056)

No hypertension (N= 1,444)

ACS (N= 1,671)

No ACS (N= 829)

Small Vessel (≤ 2.75 mm) (N= 1,253)

Large Vessel (> 2.75 mm) (N= 1,247)

Long lesion ( ≥ 28 mm) (N= 1,479)

Short lesion (< 28mm) (N= 1,021)

MVD (N= 419)

SVD (N= 2,081)

Overlapping DES (n= 147)

No overlapping DES (N= 2,353)

Multiple DES (n= 633)

Single DES (n= 1,867)

29 (3.8%)

35 (2.2 %)

28 (2.7 %)

36 (2.5 %)

41 (2.5 %)

23 (2.8 %)

45 (3.6 %)

19 (1.5 %)

47 (3.2 %)

17 (1.7 %)

19 (4.6 %)

45 (2.2 %)

11 (7.5 %)

53 (2.3 %)

27 (4.3 %)

37 (2.0 %)

0.804

0.552

0.582

1.076

0.809

1.116

1.587

0.150

2.272

1.558

1.736

3.330

2.683

8.581

10.042

1.363

MACE, n (%)

95.0% CI for Exp(B)

Lower Upper

Low incidences of MACE and ST at long-term follow-up indicates that ABLUMINUS DES+ may have encouraging safety and e�cacy in real-world unselected patients with CAD.

Logistic Regression performed for confounding factors reveals that small vessels, MVD, overlapping of stent and LM lesion had direct impact on the e�cacy and safety of the device.

Conclusion

Subgroup analysis: MACE at 1 year

The results of exploratory subgroup analysis of the primary endpoint are shown here. This analysis suggested there was no significant di�erence in MACE across all di�erent subgroups except small vessel, MVD and overlapping DES.

1.351

0.927

1.005

1.893

1.473

3.095

3.981

0.451

Hazard Ratio

0.256

0.776

0.984

0.027

0.205

0.030

0.003

0.158

p-Value

10

DIABETES MELLITUS PROMISING CLINICAL OUTCOMES IN CHALLENGING SUBGROUP

Diabetics are prone to CAD along with other conditions. Patients with CAD and DM undergoing PCI are at significantly increased risk for short and long term adverse clinical outcomes. The underlying mechanism is due to the more di�use and accelerated form of atherosclerosis and endothelial dysfunction which lead to di�used coronary lesions, small vessel disease, multi-vessel involvement, larger plaque burden as well as higher incidence of left main and ostial lesions.

Overall, 2,500 consecutive patients treated with ABLUMINUS DES were enrolled in the prospective, multi-centre, real-world “en-ABL e-Registry” and analysed according to the diagnosis of DM (859 patients) and insulin dependency (ID or NON-ID): Non-DM (1641 patients), IDDM: Insulin Dependent DM (138 patients), NIDDM: Non-Insulin Dependent DM (721 patients).

Abluminus DES+ in Diabetes Mellitus

Complex Real-world Patients

DM N=859

Age, Years ± SDMale, %Female, %

58.2 ± 12.976.024.0

Previous CV History, %

MIPCICABG

12.88.12.8

Cardiovascular Risk Factors, %

Hypertension 59.6

Clinical Presentation, %

Stable AnginaInducible IschemiaACS STEMI NSTEMI Unstable Angina

7.730.561.837.04.120.7

Extent of Coronary Artery Disease, %

1 -Vessel2-Vessel3-Vessel4-Vessel

81.117.01.90.0

RESULTS

NON-DMN=1,641

56.9 ± 12.580.419.6

11.34.81.6

33.2

5.425.169.545.94.219.4

84.313.62.00.1

NIDDMN= 721

58.1 ± 13.176.823.2

12.87.62.4

58.9

7.930.561.636.34.021.2

81.117.11.80.0

IDDMN= 138

59.1 ± 11.771.728.3

13.010.95.1

63.0

6.530.463.040.64.318.1

81.216.72.20.0

11

Baseline Lesion Characteristics

Overall PatientsNo. of lesions=2,969No. of devices=3,287

No. of Treated Lesion per patientNo. of Stents per patient

1.21.3

Target Vessel, %

Left Anterior DescendingLeft CircumflexRight Coronary ArteryRamusLeft MainBypass Graft

48.921.227.31.40.80.4

DMNo. of lesions=1,037No. of devices=1,174

1.21.4

44.323.429.41.40.90.6

1.21.3

51.319.926.21.30.80.3

1.21.4

44.023.229.81.60.90.5

NON-DMNo. of lesions= 1,932No. of devices= 2,113

NIDDMNo. of lesions= 870No. of devices= 984

IDDMNo. of lesions= 167No. of devices= 190

1.21.4

45.524.527.50.60.61.2

Lesion Details, %

Small vessel (≤2.75mm)Long lesions (≥28 mm)

47.255.2

58.955.6

40.855.0

58.555.4

61.156.9

Procedural Details, %

Pre-DilatationThrombus AspirationPost-DilatationDevice SuccessProcedure Success

68.91.843.210099.2

68.91.944.410098.9

68.81.842.510099.3

69.31.747.110099.2

67.13.029.910097.8

Device Characteristics (mm ± SD)

Mean Stent DiameterMean Stent Length

2.9 ± 0.426.8 ± 8.8

2.8 ± 0.426.5 ± 8.8

3.0 ± 0.426.9 ± 8.8

2.8 ± 0.426.5 ± 8.8

2.84± 0.426.4 ± 8.8

Cumulative Clinical Outcomes up to 1 year

DM

Patients Underwent Follow-up, NMACE, %Cardiac Death, %TV-MI, %TLR/TVR, %ST, %

8593.81.40.51.90.8

1,6412.20.80.31.10.4

1385.00.71.42.91.4

7213.51.50.31.70.7

NON-DM IDDM NIDDM

12

Time-to-event curve for the MACE and ST for the patients with DM vs. NON-DM

Time-to-event analysis for composite endpoint MACE and ST at 1 year and 2 years are presented in following Figure. The event rates presented here were calculated by Kaplan–Meier methodology.

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0 2 4 6 8 10 12

MACE: 3.8%

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Months After Index PCI

1.00

4.00

2.00

DM 855 836 823

Non-DM: 2.2%

Log Rank = 0.051

Non-DM 1,640 1,619 1,604

Pts at risk

MACE at 1 year

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0 2 4 6 8 10 12

MACE:0.8%

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Months After Index PCI

1.00

4.00

2.00

DM 855 848 848

Non-DM: 0.4%

Log Rank = 0.363

Non-DM 1,640 1,633 1,633

Pts at risk

ST at 1 year

13

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3.00

0.00

0 5 10 15 20 25

DM: 4.4%

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Months After Index PCI

1.00

4.00

2.00

DM 772 743 740

Non-DM: 2.4%

Log Rank = 0.025

Non-DM 1,474 1,439 1,438

Pts at risk

MACE at 2 years

5.00

3.00

0.00

DM: 0.9%

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Months After Index PCI

1.00

4.00

2.00

DM 772 762 761

Non-DM: 0.5%

Log Rank = 0.213

Non-DM 1,474 1,467 1,467

0 5 10 15 20 25

Pts at risk

ST at 2 years

14

Time-to-event curve for the MACE and ST for the patients with IDDM vs. NON-IDDMTime-to-event analysis for composite endpoint MACE and ST at 1 year and 2 years are presented in following Figure. The event rates presented here were calculated by Kaplan–Meier methodology.

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0 2 4 6 8 10 12

NON-IDDM: 3.5%

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Months After Index PCI

1.00

4.00

2.00

IDDM 137 133 131

IDDM: 5.0%Log Rank = 0.358

Non-IDDM 718 703 695

6.00

Pts at risk

MACE at 1 year

5.00

3.00

0.00

0 2 4 6 8 10 12

IDDM: 1.4%

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Months After Index PCI

1.00

4.00

2.00

IDDM 137 135 135

Non-IDDM: 0.7%

Log Rank = 0.636

Non-IDDM 718 714 714

Pts at risk

ST at 1 year

15

The results revealed favourable clinical safety and performance of ABLUMINUS DES+ which treats the whole diseased area in diabetic patients with its unique fusion coating technology (coated on stent and exposed parts of balloon) by reducing the rates of events through 2 years follow up.

Conclusion

16

ACUTE MYOCARDIALINFARCTIONPROMISING CLINICAL OUTCOMES IN CHALLENGING SUBGROUP

The e�cacy and safety of DES in the treatment of coronary artery disease is well established. Restenosis rates have dramatically decreased for CAD indications. Despite these results, the concern for increased (late) stent thrombosis is still present. This finding may be due to delayed vascular healing after DES implantation probably as a result of drug and/or polymer reaction. Late coronary endothelial dysfunction after DES implantation has been reported previously. Because AMI presents the highest possible thrombotic coronary lesions, DES implantation during primary percutaneous coronary intervention (PCI) for AMI is still not advocated by many interventional cardiologists. However, even in this challenging population, the use of DES has increased over the last few years. Therefore, we aimed to evaluate the safety and e�cacy of a novel Abluminus DES in patients with AMI.

Total of 2,500 patients were enrolled in en-ABL e-Registry and among them 999 patients were having AMI and 1,501 Non-AMI.

Abluminus DES+ in AMI

Complex Real-world patients:

42.3%

29.4%

32.1%

Diabetes Mellitus

Hypertension

Small Vessel

Long Lesion61.5%

Percentage of population,%

Cumulative Clinical Outcomes up to 1 year

Patients Underwent Follow-up, NMACE, %Cardiac Death, %TV-MI, %TLR/TVR, %ST, %

9992.20.80.70.71.0

1,5013.01.10.11.80.3

AMI Non-AMI

17

Time-to-event curve for the MACE and ST for the patients with AMI vs. Non-AMI

Time-to-event analysis for composite endpoint MACE and ST at 1-year and 2-years are presented in following Figure. The event rates presented here were calculated by Kaplan–Meier methodology.

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0 2 4 6 8 10 12

Non-AMI: 3.0%

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Months After Index PCI

1.00

4.00

2.00

AMI 999 989 977

AMI: 2.2%

Log Rank = 0.389

Non-AMI 1,496 1,471 1,450

Pts at risk

MACE at 1 year

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3.00

0.00

0 2 4 6 8 10 12

AMI: 1.0%

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Months After Index PCI

1.00

4.00

2.00

AMI 999 989 989

Non-AMI: 0.3%

Log Rank = 0.017

Non-AMI 1,496 1,492 1,492

Pts at risk

ST at 1 year

18

5.00

3.00

0.00

0 5 10 15 20 25

AMI: 2.6%

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Months After Index PCI

1.00

4.00

2.00

AMI 845 824 823

Non-AMI: 3.4%Log Rank = 0.373

Non-AMI 1,401 1,354 1,353

Pts at risk

MACE at 2 years

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0 4 8 12 16 24

AMI: 1.2%Cu

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Months After Index PCI

1.00

4.00

2.00

AMI 845 839 839

Non-AMI: 0.3%

Log Rank = 0.003

Non-AMI 1,401 1,393 1,393

20

Pts at risk

ST at 2 years

19

The analysis suggests that ABLUMINUS DES+ is safe and e�ective in treating patients with AMI through 2 years. A significant di�erence was found between AMI and Non-AMI cohorts in TV-MI, TLR/TVR and total ST. Significant di�erence suggests that AMI had impact on the performance of ABLUMINUS DES although for the AMI patients MACE rates and other parameters are satisfactory.

Conclusion

20

Principal InvestigatorDr. Paolo Vicinelli, Interventional Cardiologist at ASST Milano Ovest,Ospedale Civile G.Fornaroli, Magenta (MI)

en-ABL LM STUDY

ABLUMINUS DES+ IN UNPROTECTED LEFT MAIN: SINGLE CENTER EUROPEAN DATA

AIM: We have studied the 3-6-12-24-36 months clinical performance from the ultimate generation sirolimus eluting stent deployment Abluminus DES+ in patients with unprotected left main critical lesion. The peculiarity of the stent lies in the sirolimus coating technology which takes place after stent is crimped on the balloon. Total 24 patients with stenosis in left main coronary artery have been clinically and retrospectively evaluated.

METHODS: Patients undergoing left main angioplasty (24) with Abluminus DES+ stent implantation were clinically evaluated at regular intervals in order to evaluate any new symptoms that could make it necessary to perform a new coronary angiography. The target lesion of the angioplasty was the unprotected left main, either in the case it was limited to the LM ostium or in the case it involved the LAD-CFX bifurcation. Primary end point was represented by major adverse cardiac events MACE (composite of cardiac death, target vessel myocardial infarction (TV-MI), and target lesion/vessel revascularization) and definite or probable stent thrombosis.

RESULTS:  The population in the study was represented by 70.8% of male patients with an average age of 65.5 years and only 8% of cases presenting at the Emergency Room with ST elevation myocardial infarction due to LM total occlusion. Evaluating the dual antiplatelet therapy, we observed that 58.4% of the patients were treated with Clopidogrel 75 mg and Aspirin 100 mg, 41.6% with Ticagrelor 90 mg bid and Aspirin 100 mg, no patient with Prasugrel in association with Aspirin. 83 .3% of the patients presented right dominance, 65% of them with RCA critical stenosis and 23% of these with RCA total occlusion. LM lesions had an average length of 13 mm and all cases with the presence of TIMI flow 3 in baseline. After pre-dilatation, performed in 83% (20 pts.) of the patients with semi-compliant balloon 2.67 mm mean calibre, median 2.75 and mean length 14.24 mm (median 15 mm), Abluminus DES+ was implanted with a mean diameter of 3.77 mm and median 4.00 mm with mean length of 16.5 mm (median 16). Post-dilatation involved almost all patients (95 .8%, 23 pts) with a mean and median balloon size of 4 .00 mm, mean length of 9.9 mm and a median length of 11 mm.

In about 50% of cases IVUS was performed to confirm the already well angiographic-defined result. We have also evaluated the duration of the procedure and X -rays exposure which were respectively an average of 24 and 82 minutes. Procedural success was achieved in 100% of patients, no patient showed signs and/or symptoms in the 24 hours post the procedure that could be referred to periprocedural myocardial infarction.

The 36-month follow-up was achieved in all the treated patients (24) without any adverse events.

CONCLUSION: This study demonstrated the safety and e�cacy of Abluminus DES+, an ultimate generation sirolimus drug eluting stent, in the treatment of critical lesions of the unprotected left main. We can therefore state that, due to its peculiarities in coating technology, Abluminus DES+ is an excellent treatment strategy also for most complex coronary lesions.

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OngoingClinical Trials

Principal InvestigatorDr. Luca Testa, IRCCS Policlinico S. Donato, San Donato M.ne, Milan, Italy

DEDICATE REGISTRYA POST MARKET REGISTRY OF ABLUMINUS SIROLIMUS ELUTING CORONARY STENT SYSTEM FOR PERCUTANEOUS INTERVENTION IN PATIENTS WITH DIABETES MELLITUS

Design:Prospective, Observational, Multi‐center registry.

Primary Endpoint:Target Lesion Failure that is composite of Cardiac Death, Target-Vessel Myocardial Infarction, and clinically indicated Target Lesion Revascu-larization within 12 months.

Secondary Endpoint:  Stent Thrombosis [Time Frame: 1 month, 12 months, yearly];Cardiac Death [Time Frame: 1 month, 12 months, yearly];Target Vessel Myocardial Infarction [Time Frame: 1 month, 12 months, yearly];Target Lesion Revascularization [Time Frame: 1 month, 12 months, yearly];Device Success at 24 hours;Lesion Success at 24 hours;Procedural Success at 24 hours;Definite and Probable Stent Thrombosis according to ARC definitions.

MORE THAN 300 PATIENTS ARE ENROLED TILL DATE

ChairpersonDr. Francesco BedogniIRCCS Policlinico S. Donato, San Donato M.ne, Milan, Italy

Malaysia

Enroling Countries:

Italy Ireland India Romania

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Principal InvestigatorDr. Azeem Latib, San Ra�aele Hospital, Milano, Italy

ABILITY RCTRANDOMIZED CLINICAL TRIAL OF ABLUMINUS DES+ SIROLIMUS ELUTING STENT VERSUS EVEROLIMUS-ELUTING DES FOR PERCUTANEOUS CORONARY INTERVENTION IN PATIENTS WITH DIABETES MELLITUS: AN INVESTIGATOR-INITIATED PILOT STUDY

Design:Multi-centre, single-blinded, randomized, Investigator-initiated pilot clinical study. A total of 165 patients with 110 in Abluminus DES+ group and 55 in the Everolimus Eluting DES group.

Primary Endpoint:In-stent neointimal volume at 6-month follow-up, measured with OCT, following PCI with Abluminus DES+ compared with in-stent neointi-mal volume following PCI with Everolimus-eluting DES.

Secondary Endpoint:  Neointimal area, calculated at the site of minimal lumen area at 6-month follow-up measured with OCT;Target Lesion Failure;Stent Thrombosis at 12 months;Cardiac Death at 12 months;Target Vessel Myocardial Infarction;Target Lesion Revascularization;Device Success at 24 hours;Lesion Success;Procedural Success

48 PATIENTS ARE ENROLED TILL DATE

Medical DirectorProf. Antonio Colombo, Ospedale San Ra�aele, Milano, Italy

Enroling Country:

Italy

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ABILITY GLOBALRandomized Comparison of Abluminus DES+ Sirolimus-Eluting Stents versus Everolimus-Eluting Stents in Coronary Artery Disease Patients with Diabetes Mellitus

Design:Prospective, multicentre, multinational, randomized, open label, 2-arm parallel groups

Objective:To compare diabetic patients eligible for PCI with minimal exclusion criteria, the e�cacy and safety of Abluminus DES+ Sirolimus-Eluting Stents (SES) versus Everolimus-Eluting Stents (EES). At least 40% of patients are expected to be a�ected by multivessel coronary artery disease and 30% with acute coronary syndrome.

Primary Endpoint:Target lesion failure (composite of cardiac death, target vessel myocardial infarction [MI], or ischemia driven target lesion revascularization [TLR] ), powered for non-inferiority

Ischemia-driven TLR at 1-year FU (powered for non-inferiority and sequentially superiority).

Secondary Endpoint:

.

TARGET ENROLMENT: 3,000 PATIENTS

Roxana Mehran,USA

Marie-Claude Morice, France

Safety composite endpoint of the occurrence of cardiac death and target-vessel myocardial infarction (MI) at 1 year (non inferiority);In case the co-primary TLR endpoint (TLR for non-inferiority) will be demonstrated at 1 year, then the occurrence of ischemia-driven TLR at 2 year FU will be evaluated (e�cacy endpoint - superiority);Composite of cardiac death, target vessel MI and ischemia-driven TLR (TLF) at 1 year;

Others:Composite of cardiac death, target vessel MI and ischemia-driven TLR (TLF) at 2 years;Occurrence of cardiac death and target-vessel myocardial infarction (MI) at 2 years;All cause mortality up to 2 years from procedure;Stroke up to 2 years from procedure;Stent thrombosis (defined for grade and timing according to the Academic Research Consortium);Technical success;Clinical procedural success;Occurrence of ischemia-driven TLR at 2 year FU;Target vessel revascularization (TVR) up to 2 years.

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Upcoming Clinical Trial

ABBREVIATIONS:

ACS: Acute Coronary SyndromeAMI: Acute Myocardial InfractionBMS: Bare Metal StentCAD: Coronary Artery DiseaseCI: Confidence IntervalDAPT: Dual Antiplatelet TherapyDES: Drug Eluting StentDES ISR: Drug Eluting Stent In-Stent RestenosisDM: Diabetes MellitusDS: Diameter StenosisISR: In-stent restenosisLLL: Late Lumen LossLV: Large VesselMACE: Major Adverse Cardiac EventMLD: Minimal Luminal DiameterNSTEMI: Non-ST elevated Myocardial InfarctionNIH: Neo-intimal HyperplasiaOCT: Optical Coherence TomographyPCI: Percutaneous Coronary InterventionPTCA: Percutaneous Transluminal Coronary AngioplastyQCA: Quantitative Coronary AngiographyRVD: Reference Vessel DiameterSA: Stable AnginaST: Stent ThrombosisSTEMI: ST-elevated Myocardial InfarctionSV: Small VesselTLR: Target Lesion RevascularizationTLF: Target Lesion FailureTVF: Target Vessel FailureTV-MI: Target Vessel Myocardial InfarctionTVR: Target Vessel RevascularizationUA: Unstable Angina

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References :1. International Diabetes Federation 2015. IDF DIABETES ATLAS Seventh Edition. 2015; ISBN: 978-2-930229-81-2.2. Kereiakes DJ et al. J Am Coll Cardiol 2010; 56: 2084–9.3. Cutlip DE et. al. Circulation 2004; 110: 1226–30.4. Lee TT et al. Am J Cardiol 2006; 98: 718–21.5. Ryden L et al. Eur Heart J: 2013; 34:3035-87.6. Popma, J. J. et al. Circulation 110, 3773–3780 (2004).7. Van Diepen Int J Cardiol: 2013; 168:5162-6.8. Eur Card Dis 2006 (2): 2006:2(2):50-53

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