A Novel Abluminal Coated Sirolimus-Eluting Stent as a Treatment Option for Diabetic Patients: Results from an All-Comers Multi-center Study: the En-ABL registry featuring the ABLUMINUS DES + Dr. Luca Testa, MD, PhD Head of Coronary Revascularisation unit Head of Clinical Research Unit Dept. of Cardiology IRCCS Policlinico S. Donato, Milan, Italy luctes@gmail.com

BACKGROUND Coronary artery disease is the main cause of morbidity and mortality in diabetics. As compared to non diabetics: CAD is usually more complex and diffuse CAD has earlier presentation CAD has a worse outcome PCI is less effective for a higher rate of ISR and ST

DES CLINICAL OUTCOME IN DIABETIC PATIENTS - Available DES, including the latest “-olimus” generations, have shown lower angiographic efficacy in diabetic patients compared to non-diabetics. - The 2nd generation DES has failed to prove higher efficacy in diabetic patients versus 1st generation DES

ABLUMINUS DES+ is a product of Ënvisõlution Technology It is a highly effective drug delivery technology with a specific coating configuration: - abluminal on stent, - and on exposed parts of the balloon

ABLUMINUS DES+ is a product of Ënvisõlution Technology Envisõlution Coating Spray coating on stent to achieve abluminal coating Only outer surface towards vessel wall is coated Drug is coated on stent as well as exposed parts of balloon Ënvisõlution Technology Fusion of DES with DCB Edge restenosis is addressed by coating 0.5mm from distal and proximal parts of stent Addresses current problem of focal restenosis caused due to existing 14-20% of metal: artery ratio Luminal surface remains drug free Directional drug release …… better re-endothelialization! Customized PLLA polymer has smooth and homogenous degradation in vessel wall when it comes in contact with blood vessel Biodegradable polymer matrix Conversion from DES to BMS in 180 days

En-ABL Registry Study Design Objective Primary Endpoint Secondary Endpoint Prospective, multi-center, real world, all comers Evaluate the safety and efficacy performances of Abluminus DES+, in real world-all comers patients population, with a specific focus on diabetics subjects Major Adverse Cardiac Event* (MACE) at 1-Year follow-up * Composite of cardiac death, target vessel MI, Target Lesion/ Vessel Revascularization (TLR/ TVR). Stent Thrombosis (ST) according to the ARC definition; MACE assessed up to 2 years.

Study status Baseline 2100 patients* Sub-study Diabetics 750 patients 1 year follow-up 637 patients Angiographic follow-up in 32 patients has been done at mean time of 10 months 2 year follow-up 454 patients 1 Month follow-up 1 year follow-up 2 years follow-up 2100 patients* 1744 patients* 1260 patients* * Enrollment and follow-up ongoing.

Challenging population and procedural characteristics in Diabetics No. of Patients = 750 Age, (Mean ± SD) 59.28 ± 9.66 Male, (%) 76.40 Cardiovascular Risk Factors, (%) Hypertension 60.53 Renal insufficiency 3.20 Previous CV History, (%) MI 13.60 PCI 6.93 CABG 2.27 Clinical Presentation, (%) Stable Angina 40.53 STEMI 34.40 NSTEMI 3.47 Unstable Angina 21.60 No. of lesions=907, No. of Device= 1010 Number of lesions per patient,% 1.21 Number of device per patient,% 1.35 Lesions per patient, % 1 Lesion 80.80 2 Lesions 17.47 3 Lesions 1.73 Long lesions (≥28 mm) 53.03 Small vessels (RVD ≤2.75 mm) 57.33 Device details Mean stent diameter (mm) 2.93 ± 0.42 Mean stent length (mm) 26.50 ± 8.77

Safety and efficacy in Diabetics vs. Non-diabetics All Ps>0.05 All Ps>0.05

Diabetic population matched to performance goal patient population Performance goal based on DES trials meta-analysis: DIABETES, RAVEL DM, SIRIUS DM, TAXUS IV, SCORPIUS, and ENDEAVOR pooled diabetic patients.

Comparison of safety and efficacy with other DES #MACE (Major Adverse Cardiac Events), defined as composite of Cardiac death, Target Vessel- MI or Target Lesion/Vessel Revascularization (TLR/TVR). TLF (target Lesion Failure) was the main study endpoint for SPIRIT IV, which had similar components of MACE described above. TVF (target Vessel Failure) was the main study endpoint for EVOLVEII, which had similar components of MACE described above. *Outcomes in Diabetic and Nondiabetic Patients Treated with Everolimus or Paclitaxel- Eluting stents. JACC Vol. 56, No. 25, 2010: 2084-9. **Primary clinical outcomes of the EVOLVE II Diabetes substudy evaluating a novel bio absorbable polymer-coated, Everolimus-eluting coronary stent in Diabetic Patients. S. Windecker, euro PCR 2015 presentation.

What are the possible mechanisms underlying these results?

The double administration of the –limus drug (?)

What does the future hold?

Principal Investigator DEDICATE Registry A NOVEL DRUG ELUTING STENT FOR DIABETIC PATIENTS IN CORONARY ARTERY DISEASE TREATMENT Prospective, Spontaneous, Observational, Multi‐center clinical registry Real-world all-comer patients treated with ABLUMINUS DES+ 1000 patients at 20-30 sites across the globe Principal Investigator Dr. Luca Testa, MD, PhD

“ABILITY” RANDOMIZED CLINICAL TRIAL A Randomized clinical trial of Abluminus DES+ versus Xience EES for Percutaneous Coronary Intervention in patients with Diabetes Mellitus: a pilot study Randomized multi-centre single-blinded controlled clinical trial A total of 140 patients will be enrolled Angiographic endpoints of struts coverage/endhotelialisation at 6 months Principal Investigator Prof. Antonio Colombo San Raffaele Hospital,Milano, Italy

CONCLUSION Envisõlution™ technology provides better drug delivery to optimise the performance: it merges the advantages of a DCB and a polymer free DES The results of this real-world multicentre study show that Abluminus DES+ has optimal safety and efficacy profile in DM patients. The ABLUMINUS DES+ is the first DES to have consistent results in both diabetic and non diabetic patients. In terms of MACE the ABLUMINUS DES+ seems even superior to current standard of care DES While waiting for larger prospective data, the ABLUMINUS DES+ can be rightfully deemed as very promising alternative for diabetics.

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