Final Five-year Outcomes from the Randomized Comparison of - PowerPoint PPT Presentation

Final Five-year Outcomes from the Randomized Comparison of Zotarolimus-eluting Stents With Everolimus-eluting Stents in the RESOLUTE All Comers Trial Stephan Windecker Swiss Cardiovascular Center and Clinical Trials Unit Bern Bern University Hospital, Switzerland on behalf of the RESOLUTE All Comers Investigators PCR2014

Potential conflicts of interest Speaker's name: Stefan Windecker  I have the following potential conflicts of interest to report: Institutional grant/research support: Research grants to the institution from Biotronik and St Jude

RESOLUTE All Comers Background • New generation drug-eluting stents have improved safety and effectiveness outcomes for patients with coronary artery disease undergoing percutaneous coronary intervention. • Longer-term follow-up for new generation DES remains incomplete and may provide additional information especially in patients with complex coronary artery disease. • The RESOLUTE All Comers trial was the first randomized trial comparing the Resolute zotarolimus-eluting stent (R-ZES) with the XIENCE V everolimus-eluting stent (EES) in an all- comers patient population. • We evaluated 5-year outcomes to determine whether clinical equivalence between the two stent types were maintained at longer follow-up.

RESOLUTE Global Clinical Program Enrollment Complete - In Follow Up RESOLUTE 1 Non-RCT First-in-Human (R=139) 5 yr RESOLUTE AC 2,3 1:1 RCT vs. Xience V ™ EES (R=1140; X=1152) 5 yr RESOLUTE Int 4,5 Non-RCT Observational (R=2349) 3 yr RESOLUTE US 6 2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402) 4 yr RESOLUTE Japan 2.5 – 3.5 mm Non-RCT (R=100) vs. Hx Control 3 yr R-Japan SVS 2.25 Non-RCT vs. PG (R=65) 2 yr RESOLUTE US 7 38 mm sub-study Non-RCT vs. PG (R=114) 1 yr R-China RCT 8 1:1 RCT vs. Taxus ™ PES (R=200; T=200) 1 yr RESOLUTE Asia 7 Non-RCT Observational (R=312) 1 yr Non-RCT Observational (R=1800) R-China Registry 9 1 yr Enrolling / Planning RI-US Registry Post-approval study (RI≈230) enrolling PROPEL Post-approval study (RI=1200) vs. Hx Control enrolling 1 Meredith IT, et al. EuroIntervention. 2010;5:692-7. 2 Serruys PW, et al. N Engl J Med. 2010;363:136-46. 3 Silber S, et al. Lancet. 2011;377:1241-47. 4 Neumann FJ, et al. EuroIntervention . 2012;7(10):1181-8. 5 Belardi JA, et al. J Interv Cardiol . 2013;26(5):515-23. 6 Yeung AC, et al. JACC . 2011;57:1778-83. 7 Lee M, et al. Am J Cardiol. 2013;112(9):1335-41. 8 Xu B, et al. JACC Cardiovasc Interv . 2013;6(7):664-70. 9 Qiao S, et al. Am J Cardiol . 2013. doi: 10.1016/j.amjcard.2013.10.042. [Epub ahead of print]

RESOLUTE All Comers Clinical Trial Design Co-PIs: Profs. Serruys, Silber, Windecker Open label, non-inferiority trial Any patient with symptomatic coronary artery disease eligible for DES implantation (no lesion/vessel limitations) 17 European sites Resolute ™ Stent Xience V ™ Stent 2300 patients randomized 1:1 n = 1150 n = 1150 Subsets: QCA 460 pts (20%); OCT 50 pts (2%) 100% monitoring Clinical endpoints 30d 6mo 12mo 13mo 2yr 3yr 4yr 5yr Angio/OCT endpoints Primary Endpoint: • 12-month target lesion failure (TLF), composite of cardiac death, target vessel MI & clinically driven TLR Secondary Endpoints: • Clinical: Patient composite of any death, any MI, & any repeat revascularisation • QCA (powered): 13-month in-stent % diameter stenosis • QCA: % diameter stenosis, late loss, and binary restenosis Drug Therapy: ASA and clopidogrel/ticlopidine > 6mo (per guidelines) Serruys PW, et al., N Engl J Med. 2010;363(2):136-46

RESOLUTE All Comers Patient Flow Chart Patients Enrolled N = 2292 Resolute ™ (R-ZES) Xience V ™ (EES) Randomized 1:1 N = 1140 N = 1152 n = 1132 n = 1142 1 Yr Follow-up 99.3% 99.1% n = 1128 n = 1139 2 Yr Follow-up 98.9% 98.9% n = 1128 n = 1137 3 Yr Follow-up 98.9% 98.7% n = 1127 n = 1135 4 Yr Follow-up 98.9% 98.5% n = 1123 n = 1133 5 Yr Follow-up 98.5% 98.4%

RESOLUTE All Comers Baseline Characteristics Resolute ZES Xience V EES (N = 1140) (N = 1152) P value Age (yr) 64.4 ± 10.9 64.2 ± 10.8 0.70 Men (%) 76.7 77.2 0.80 Diabetes mellitus (%) 23.5 23.4 1.00 IDDM 8.4 7.1 0.28 ACS (%) 48.3 47.7 0.80 AMI (within 12 hr) (%) 15.4 17.8 0.13 AMI (within 72 hr) (%) 28.9 28.8 0.96 Multivessel disease (%) 58.4 59.2 0.73 Small vessel (RVD ≤2.75 mm) 67.8 67.4 0.88 Long lesion (length >18 mm) 18.2 21.2 0.11 Bifurcation/trifurcation (%) 16.9 17.7 0.62 Total occlusion (%) 16.3 17.2 0.61 In-stent restenosis (%) 8.1 8.0 0.94 Complex Patients 1 (%) 67.0 65.6 0.51 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 (preprocedure TIMI = 0). Serruys PW, et al., N Engl J Med. 2010;363(2):136-46.

RESOLUTE All Comers Procedure Characteristics Resolute ZES Xience V EES N = 1140 patients, N = 1152 patients, 1661 lesions 1705 lesions P value Lesions treated per patient 1.5 ± 0.7 1.5 ± 0.8 0.46 Lesion length (mm) 11.9 ± 7.5 12.2 ± 7.9 0.38 No. of stents per patient 1.9 ± 1.2 2.0 ± 1.3 0.02 Stent length per patient (mm) 34 ± 24 37 ± 26 0.02 Pre-stent balloon dilatation 69.5% 70.2% 0.75 Deployment pressure 14.9 ± 3.1 15.1 ± 3.2 0.01 Implantation of study stent only 98.0% 96.9% 0.11 Lesion success 98.9% 99.1% 0.62 Device success 97.0% 96.6% 0.52 Procedure success 94.6% 94.2% 0.78 Serruys PW, et al., N Engl J Med. 2010;363(2):136-46.

RESOLUTE All Comers Target Lesion Failure to 5 Years 40 Resolute ™ ZES (N = 1140) Log rank P = 0.65 Xience V ™ EES (N = 1152) Cumulative Incidence 30 of TLF (%) Primary endpoint P non-inferiority <0.001 20 17.1% 8.3% 16.3% 8.2% 10 0 0 1 2 3 4 5 Time After Initial Procedure (years) No. at risk Resolute 1140 1110 1035 992 960 920 Xience V 1152 1122 1031 995 959 926 TLF (Target Lesion Failure) is defined as cardiac death, TVMI, or clinically driven TLR.

RESOLUTE All Comers Target Lesion Failure Components at 5 Years Resolute ™ ZES (n = 1123) Xience V ™ EES (n = 1133) P = 0.58 P = 1.00 P = 0.48 TLR is clinically driven.

RESOLUTE All Comers DAPT * Usage over 5 Years Resolute ™ ZES (N = 1140) Xience V ™ EES (N = 1152) DAPT Usage (%) 12.3% 11.3% Time After Initial Procedure (months) * Aspirin and (Clopidogrel or Ticlopidine or Prasugrel or Ticagrelor) P -value is not significant at all time points.

RESOLUTE All Comers Stent Thrombosis to 5 Years: Definite 10 Resolute ™ ZES (N = 1140) Log rank P = 0.08 Xience V ™ EES (N = 1152) Cumulative Incidence of 8 ARC Definite ST (%) 6 4 2 1.62% 0.82% 0 0 1 2 3 4 5 Time After Initial Procedure (years) No. at risk Resolute 1140 1135 1100 1075 1049 1011 Xience V 1152 1150 1105 1084 1054 1024

RESOLUTE All Comers Very Late Stent Thrombosis: Definite 5 Resolute ™ ZES (N = 1140) Log rank P = 0.76 Very Late ARC Definite ST (%) Xience V ™ EES (N = 1152) Cumulative Incidence of 4 3 2 1 0.56% 0.47% 0 1 2 3 4 5 Time After Initial Procedure (years) No. at risk Resolute 1111 1111 1086 1060 1022 Xience V 1108 1108 1087 1057 1027

RESOLUTE All Comers Stent Thrombosis to 5 Years: Definite / Probable 10 Resolute ™ ZES (N = 1140) Log rank P = 0.22 ARC Definite/Probable ST (%) Xience V ™ EES (N = 1152) Cumulative Incidence of 8 6 4 2.4% 2 1.7% 0 0 1 2 3 4 5 Time After Initial Procedure (years) No. at risk Resolute 1140 1134 1098 1072 1044 1005 Xience V 1152 1150 1104 1083 1051 1021

RESOLUTE All Comers Very Late Stent Thrombosis: Definite / Probable 5 Resolute ™ ZES (N = 1140) Cumulative Incidence of Very Late Log rank P = 0.66 ARC Definite/Probable ST (%) Xience V ™ EES (N = 1152) 4 3 2 1.03% 1 0.84% 0 1 2 3 4 5 Time After Initial Procedure (years) No. at risk Resolute 1111 1111 1085 1057 1018 Xience V 1108 1108 1087 1055 1025

RESOLUTE All Comers TLF Subset Analysis at 5 Years Odds Subset N Ratio 95% CI P-value Complex 1520 0.99 0.80–1.23 0.95 Small vessel 1308 1.01 0.79–1.28 1.00 (≤2.75 mm) Multi-vessel 570 0.92 0.66–1.29 0.67 treatment Diabetes 538 1.07 0.79–1.47 0.68 Bifurcations 392 1.03 0.67–1.57 1.00 Long Lesions 381 0.85 0.53–1.34 0.49 (>18 mm) STEMI 280 0.74 0.34–1.61 0.53 ISR 182 0.81 0.52–1.25 0.42 0.1 Favors R-ZES 1.0 Favors EES 10.0 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 (preprocedure TIMI = 0).

RESOLUTE All Comers Final Conclusions • The follow-up compliance at 5 years was extremely high (98.5%), further supporting the reliability of these long term study outcomes in an all-comer patient population. • In this predominantly complex patient population, both stents remained clinically equivalent through 5 years (TLF 17.1% vs. 16.3%, P = 0.65). • Despite that only ~10% of patients were on DAPT at 5 years, the incidence of very late stent thrombosis is low and similar between Resolute ZES and Xience V EES (def/prob ST 0.84% vs. 1.03%, P = 0.66).