A Randomized Trial of a Bioabsorbable Polymer-Based Metallic DES vs. - PowerPoint PPT Presentation

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.

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

Elderly PCI patients • CAD is highly prevalent: complex, severe, and diffuse • In US national registries in 2016 1 : 25% of PCI in patients ≥ 75y • Poorly represented in prior studies on DES and DAPT duration • No clear recommendation for PCI strategies Often treated with BMS and short DAPT (*), as a strategy to limit bleeding complications 2 (*) Short DAPT: 1mo in stable patients, ≥ 6mo in unstable patients (per ESC guidelines) 1. Masoudi FA, et al. JACC 2017;69:1424-6 2. Gerber Y, et al. J Interv Cardiol . 2017;30:347-55

Drug-coated Stents Subgroup analysis: elderly patients 1. Urban P. et al. N Engl J Med . 2015;373:2038-47 2. Morice MC. et al. Int J Cardiol . 2017;243:110-115

SENIOR Study Hypothesis To demonstrate that a thin struts DES & short BMS-like 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 ) www.ClinicalTrial.gov: NCT NCT02099617

SENIOR Trial design Randomized (1:1), single blind trial 1,200 patients aged 75 years and above Tailored DAPT: 1 mo in stable and 6 mo in ACS pts Prespecified by the investigator prior to randomization DES BMS Vs. Primary End Point 1y: all-cause mortality, non-fatal MI, stroke, IDTLR Secondary End Points 1y: Bleeding BARC 2-5/3-5, stent thrombosis Varenne O. et al. EuroIntervention . 2017;12(13):1614-22

Synergy™ DES used in SENIOR 74µm Everolimus SEM of coating BMS PLGA Polymer (x5000) Meredith I. et al. EuroInterv 2017 (in Press) doi:10.4244/EU-D-17-00529

Key Inclusion Criteria • Patients are 75 years old or above and • Presence of ≥ 1 stenosis ( ≥ 70%) in any coronary (or LM ≥ 50%) and - Stable angina or - Silent ischemia or - Acute coronary syndrome

Key Exclusion Criteria • Unable to comply with DAPT for at least one month (stable angina or silent ischemia) or at least six months (acute coronary syndrome) • Planned surgery within one month • Life expectancy less than 1 year • Prior hemorrhagic stroke • Indication for surgical myocardial revascularization • Known allergy to aspirin or any P2Y 12 inhibitor

1,200 pts ≥ 75 years with CAD Intended DAPT: 1 mo (57%) and 6 mo (43%) DES BMS R N=596 N=604 10 pts (1.7%): withdrew 6 pts (1.0%): withdrew 2 pts (0.3%): lost to FU 6 pts (1.0%): lost to FU MACCE 1y N=1,176 (98%)

Baseline Characteristics DES BMS N=596 N=604 Age, y 81.4±4.3 81.4±4.2 Male sex, % 61.7 62.7 BMI, kg/m 2 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

Clinical Presentation DES BMS 10.3 10.9 19.7 20.3 25.8 25.5 35.6 33.3 8.6 9.6 Stable angina Silent Ischemia STEMI NSTEMI UA

Angiography DES BMS N=596 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 3.0±0.5 Total stent length per patient (mm) 32.6±20.8 30.3±20.3 *P <0.05

DAPT duration 100% % of Patients on DAPT (%) Log-rank test 90% P=0.77 Patients on DAPT (%) 80% 70% 60% 50% 40% 30% BMS 20% DES 10% 0% 0 1 2 3 4 5 6 7 8 9 10 11 12 Months since Randomisation Number at risk 596 482 269 256 249 240 214 102 92 89 87 87 0 Drug-eluting stent 604 482 263 251 249 247 213 112 102 95 93 92 0 Bare-metal stent

Primary End Point All-cause mortality, MI, stroke, ischemia-driven TLR 18 16.4 % Log rank 15 P=0.0160 BMS Primary EP (%) 11.6 % 12 9 DES 6 RR 0.71 (95%CI 0.52-0.94) 3 NNT 21 0 0 50 100 150 200 250 300 350 400 Days

MACCE Components 20 P=0.0172 16.4 DES Patients (%) 15 BMS 11.6 10 P=0.20 P=0.0002 8 P=0.92 5 6.1 5.9 P=0.08 3.6 3.7 2 1.7 0.8 0 Mortality Stroke MI ID-TLR MACCE

Safety Endpoints 6 P=0.68 5 DES Patients (%) 5.0 P=0.86 4.5 4 BMS 3.5 3.6 3 P=0.13 2 1.4 1 0.5 0 BARC 2-5 BARC 3-5 ST (def+prob)

Net Clinical Benefit MACCE and BARC 2-5 21% 19.2 % Log-rank test 18% BMS P=0.0239 Patients (%) 15% 14.4 % 12% DES 9% 6% RR 0.75, 95% CI 0.58-0.97 3% 0% 400 0 50 100 150 200 250 300 350

Impossible d'a ffj cher l'image. Votre ordinateur manque peut-être de mémoire pour ouvrir l'image ou l'image est endommagée. Redémarrez l'ordinateur, puis ouvrez à nouveau le fichier. Si le x rouge est toujours a ffj ché, vous devrez peut-être supprimer l'image avant de la réinsérer. Subgroup Analyses (primary end point) DES BMS All-cause mortality, MI, stroke, DES BMS Relative Risk DES BMS Better Better ischaemia-driven TLR at 1 year (N=596) (N=604) (95% CI) P-value Better Better Overall event rate 68/545 ( 11 · 6%) 98/568 ( 16 · 4%) 0 · 7 ( 0 · 5, 0 · 9) 0 · 016 Age [years] (Interaction: p=0 · 587) <85 48/419 ( 10 · 5%) 71/429 ( 15 · 7%) 0 · 7 ( 0 · 5, 0 · 9) 0 · 022 >= 85 20/126 ( 15 · 1%) 27/139 ( 18 · 7%) 0 · 8 ( 0 · 4, 1 · 4) 0 · 426 Atrial fibrillation (Interaction: p=0 · 025) No 44/448 ( 9 · 1%) 77/466 ( 15 · 8%) 0 · 6 ( 0 · 4, 0 · 8) 0 · 001 Yes 24/ 95 ( 23 · 8%) 21/101 ( 19 · 5%) 1 · 2 ( 0 · 7, 2 · 1) 0 · 452 Acute coronary syndrome (Interaction: p=0 · 315) No 30/297 ( 9 · 4%) 52/312 ( 15 · 7%) 0 · 6 ( 0 · 4, 0 · 9) 0 · 015 Yes 38/248 ( 14 · 1%) 46/256 ( 17 · 3%) 0 · 8 ( 0 · 5, 1 · 2) 0 · 312 Sex (Interaction: p=0 · 105) Male 38/341 ( 10 · 4%) 67/357 ( 17 · 9%) 0 · 6 ( 0 · 4, 0 · 8) 0 · 003 Female 30/204 ( 13 · 4%) 31/211 ( 13 · 8%) 1 · 0 ( 0 · 6, 1 · 6) 0 · 900 Percentages are Kaplan-Meier estimates · 0 0 · 5 1 1 · 5 2 2 · 5

Summary The SENIOR trial evaluated a bioabsorbable polymer DES vs. BMS in elderly patients treated with short DAPT • MACCE was lower with DES (11.6% vs 16.4%, p=0.0172) • This was mainly driven by ID-TLR (1.7% vs 5.9%, p=0.0002) • DAPT duration and bleeding were similar in the two groups • ST was low and not different (0.5% vs 1.4%, p=0.12) All TVT 2016 faculty disclosures are listed online and on the app.

Conclusion PCI with a contemporary thin struts 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.

Top Enrolling Centers Investigator Center Nb 1- G. Sideris ASAPH, APHP centers, Paris - Fr 334 2- S. Cook Université de Fribourg, Fribourg - CH 148 3- S. Kedev University Clinic of Cardiology, Skopje - MC 93 4- T. Cuisset Hôpital de la Timone, Marseille - Fr 74 5- D. Carrié CHU Rangueil, Toulouse - Fr 72 6- T. Hovasse Hôpital Privé Jacques Cartier, Massy - Fr 70 7- P. Garot Hôpital Privé Claude Galien, Quincy - Fr 59 8- J. Diaz Juan Ramon Jimenez Hospital, Huelva - SP 29 9- S. Brugaletta Hospital Clinic, Barcelona - SP 28 10- E. Pinar Hospital Universitario Virgen de la Arrixaca, Murcia - SP 24 11- F. Mauri Hospital Universati Germans Trias i Pujol, Badalona - SP 22 12- P. Commeau Polyclinique les Fleurs, Ollioules - FR 21

Trial Organization PI and coPIs O.Varenne (PI), P. Sinnaeve (CoPI), T. Cuisset (CoPI) Executive O.Varenne, P. Sinnaeve, T. Cuisset, M. Sabate and M-C. Committee Morice Statistics Ann Belmans and K. Bogaerts DSMB ME. Bertrand (chair), J. Berland, A. Waqar. CEC A. Chieffo (chair), T. Royer, A. Pichard, B. Valeix, J. Machecourt, J. Garot, L. Levai, C. Macaya, J. Ramón Rumoroso, V. Domigo, P. Kearney, R. Mehran, J. Escaned. CRO CERC, Massy, France (Project Leader A. Sequeira) E-CRF CLINIGRID, Paris, France. Sponsor CERIC through a grant from Boston Scientific