A Randomized Trial of a Bioabsorbable Polymer-Based Metallic DES vs A Randomized Trial of a Bioabsorbable Polymer-Based Metallic DES vs. a BMS with Short DAPT in Patients with Coronary Artery Disease Older than 75 Years. The SENIOR Trial O. Varenne, S. Cook, G. Sideris, S. Kedev, T. Cuisset, D. Carrié, T. Hovasse, P. Garot, R. El Mahmoud, C. Spaulding, G. Helft, J. Diaz Fernandez, S. Brugaletta, E. Pinar Bermudez, J. Mauri Ferre, P. Commeau, E. Teiger, K. Bogearts, M. Sabate, M-C. Morice and P. Sinnaeve, for the SENIOR investigators. Dear Chairmen, Ladies and Gentlemen, It’s a real pleasure, and a great honor to be here today, and to present, on behalf of my coinvestigators, the results of the SENIOR trial, a randomized trial of a bioabsorbable polymer based metallic DES vs. a BMS with a short DAPT in patients with coronary artery disease older than 75 years.

Disclosure Statement of Financial Interest Within the past 12 months, I or my partner have had a financial interest with the organizations listed below Financial Relationship Company Lectures Fees Boston Scientific Abbott Vascular Astra Zeneca Servier These are my conflicts of interest.

SENIOR Study Hypothesis To demonstrate that a bioabsorbable polymer DES & short DAPT in elderly patients is associated with: - a lower rate of MACCE at 1 year vs. BMS (efficacy) - a similar risk of bleeding at 1 year vs. BMS (safety) - a similar risk of stent thrombosis at 1 year vs. BMS (safety) In SENIOR, we wanted to demonstrate that the latest generation, thin struts, bioabsorbable polymer DES with short, BMS-like DAPT in elderly could be associated with - a lower rate of MACCE at 1 year -and a similar risk of bleeding, and stent thrombosis than current, thin struts BMS. www.ClinicalTrial.gov: NCT NCT02099617

Intended DAPT: 1 mo (57%) and 6 mo (43%) 1,200 pts ≥75 years with CAD Intended DAPT: 1 mo (57%) and 6 mo (43%) DES N=596 BMS N=604 R 10 pts (1.7%): withdrew 2 pts (0.3%): lost to FU 6 pts (1.0%): withdrew 6 pts (1.0%): lost to FU MACCE 1y N=1,176 (98%) 1200 patients were included. Intended DAPT was 1 mo in 56.9% and 6 mo in 43.1% of the patients, respectively. Patients were then randomized 1:1 to DES or similar BMS. A total of 12 patients in each group did not attempt 1 year because they were lost to FU or because they withdrew their consent. Therefore MACCE evaluation at one year was performed in 1176 patients, 98% of the included patients.

Synergy™ DES used in SENIOR 74μm Everolimus PLGA Polymer SEM of coating (x5000) BMS This is the DES that we used in SENIOR. The SYNERGY stent from BSCI is a thin, 74 µm struts, platinum chromium alloy plateform. The struts are covered with a abluminal bioabsorbable polymer eluting everolimus with a synchronized drug release and polymer absorption. It has been shown to be non inferior to durable polymer everolimus DES at 1 year and up to 5 years with no reported stent thrombosis in the recently published EVOLVE trial. The BMS is also a thin strut metallic plateform, very similar to the DES. Meredith I. et al. EuroInterv 2017 (in Press) doi:10.4244/EU-D-17-00529

Baseline Characteristics DES N=596 BMS N=604 Age, y 81.4±4.3 81.4±4.2 Male sex, % 61.7 62.7 BMI, kg/m2 26.3±4.3 25.9±3.9 Diabetes mellitus, % 26.6 26.0 Hypercholesterolemia, % 52.2 53.0 Hypertension*, % 71.6 80.8 Previous MI*, % 18.3 13.3 PVD*, (%) 14.7 21.0 Atrial fibrillation, % 17.3 17.9 Anemia, % 13.8 15.0 *P <0.05 These are the baseline characteristics of the patients. Patients were 81y in both groups. They were male in more than 60%. Patients have a high cardiovascular risk including HTN, HCHO, DM, RI, and anemia in 75%52%, 26%, 17% and 14%. Please note that more patients with a prior MI were treated with DES and more patients with HTN and peripheral vascular disease were treated with BMS.

Clinical Presentation DES BMS Stable angina Silent Ischemia STEMI NSTEMI UA Clinical presentation was similar in both group. Roughly 55% of the patients were included for a stable condition including stable angina despite medical therapy and silent ischemia. Unstable presentation was present in 45% of the patients. STEMI and Unstable angina represent almost 10% each and NSTEMI represent a quarter of all patients.

Angiography Transradial approach, % 79.8 81.3 DES N=596 BMS N=604 Transradial approach, % 79.8 81.3 Multiple vessel disease, % 34.0 30.6 Lesion location, %   LM* 3.9 1.3 LAD 54.0 52.3 LCx 29.8 26.5 RCA 35.9 37.9 Stents implanted per patient  1.7±1.0  1.6±1.0 Stent diameter per lesion (mm) 3.0±0.5 Total stent length per patient (mm) 32.6±20.8 30.3±20.3 *P <0.05 Angiography at baseline showed complex lesions. Please note that a trans radial approach was used in 80% of the PCI. A third of patients had multivessel disease. Lesion locations were well balanced except for LM stenosis more frequently treated with DES. Patients received a mean of 1.7 stents, of a 3.0 diameter. Stent length per lesion was 19mm and total stent length per patient was 30-32mm.

DAPT duration BMS DES Log-rank test P=0.77 % of Patients on DAPT (%) Importantly, and because it was not randomized, this slide shows DAPT duration in both BMS and DES throughout the entire trial. Please note that the two curves are VIRTUALLY SUPERIMPOSABLE with a p value of 0.77. As you can see, there is a first fall around 1 month corresponding to stable patients stopping their thienopyridine and a second fall at 6 months where ACS patients stopped P2Y12 inhibitor. There are a bit more than 15% of the patients remain on DAPT after 6 months with no difference between the two groups..

All-cause mortality, MI, stroke, ischemia-driven TLR Primary End Point All-cause mortality, MI, stroke, ischemia-driven TLR 18 15 12 9 6 3 16.4 % Log rank P=0.0160 BMS 11.6 % Primary EP (%) DES RR 0.71 (95%CI 0.52-0.94) NNT 21 And this is, for the first time, the primary endpoint analysis of the SENIOR trial at one year. DES were associated with a dramatic reduction in MACCE at one year compared to similar BMS.: 11.6% vs. 16.4% This is a 29% reduction, highly significant with a p value of 0.0160. The number needed to treat to avoid one MACCE at 1 year is 21 pts. Please note that the two curves are still diverging at one year. I am looking forward for the pre defined analysis of PEP at 2 years. 50 100 150 200 250 300 350 400 Days

MACCE Components DES BMS Patients (%) P=0.0172 P=0.20 P=0.0002 P=0.92 When looking at the components of the primary endpoint. All cause mortality, stroke and MIs were not significantly different between the two groups. The benefit of DES is related to a 71% reduction in ID TLR: 1.7% in the DES group and a remarkable 5.9% in the BMS group. The p value is highly significant 0.0002. What About safety?

Safety Endpoints DES BMS Patients (%) The similar DAPT duration in both groups led to the following safety parameters: Bleeding BARC2-5 were 4.5 and 5.0%, similar between the two groups Bleeding 3-5 were 3.5 and 3.6% and also similar between DES and BMS Definite and probable stent thrombosis were rare and extremely low in the DES group despite the reduced DAPT 0.5%, numerically lower but not significantly different compared to BMS 1.4%.

Conclusion PCI with a contemporary bioabsorbable polymer DES is more effective, and as safe as BMS in elderly patients with CAD, on a short DAPT tailored to their clinical presentation BMS should no longer be used as a strategy to reduce DAPT duration in elderly patients All TVT 2016 faculty disclosures are listed online and on the app. ---------------------------- And to conclude, Mister Chairmen, I think it is fair to say, that SENIOR demonstrates that PCI with a contemporary bioresorbable polymer DES is more effective, and as safe as BMS in elderly patients with CAD, on a short DAPT tailored to their clinical presentation Finally, I strongly belive that BMS should no longer be used as a strategy to reduce DAPT duration in these patients