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

• n 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

• 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.

Background

RESOLUTE All Comers

RESOLUTE Global Clinical Program

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. 5Belardi JA, et al. J Interv Cardiol. 2013;26(5):515-23. 6Yeung AC, et al. JACC. 2011;57:1778-83. 7Lee M, et al. Am J Cardiol. 2013;112(9):1335-41. 8Xu B, et al. JACC Cardiovasc Interv. 2013;6(7):664-70. 9Qiao S, et al. Am J Cardiol. 2013. doi:

10.1016/j.amjcard.2013.10.042. [Epub ahead of print]

Enrollment Complete - In Follow Up

RESOLUTE1

Non-RCT First-in-Human (R=139) 5 yr

RESOLUTE AC2,3

1:1 RCT vs. Xience V™ EES (R=1140; X=1152) 5 yr Non-RCT Observational (R=2349) 3 yr 2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402) 4 yr

RESOLUTE US6

2.5 – 3.5 mm Non-RCT (R=100) vs. Hx Control

RESOLUTE Japan

3 yr

RESOLUTE Asia7

Non-RCT Observational (R=312) 1 yr

RI-US Registry

Post-approval study (RI≈230) enrolling Enrolling / Planning 1:1 RCT vs. Taxus™ PES (R=200; T=200)

R-China RCT8

1 yr

RESOLUTE Int4,5 R-China Registry9

Non-RCT Observational (R=1800) 1 yr

R-Japan SVS

2.25 Non-RCT vs. PG (R=65) 2 yr 38 mm sub-study Non-RCT vs. PG (R=114) 1 yr

RESOLUTE US7 PROPEL

Post-approval study (RI=1200) vs. Hx Control enrolling

RESOLUTE All Comers

17 European sites 2300 patients randomized 1:1 Subsets: QCA 460 pts (20%); OCT 50 pts (2%) 100% monitoring

Clinical endpoints Angio/OCT endpoints

Co-PIs: Profs. Serruys, Silber, Windecker

Clinical Trial Design

Open label, non-inferiority trial Any patient with symptomatic coronary artery disease eligible for DES implantation (no lesion/vessel limitations) Resolute™ Stent n = 1150 Xience V™ Stent n = 1150

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

30d 6mo 4yr 3yr 2yr 12mo 13mo 5yr

Patient Flow Chart

RESOLUTE All Comers

Randomized 1:1 Resolute™ (R-ZES) N = 1140 n = 1132 99.3% n = 1128 98.9%

Patients Enrolled

N = 2292 Xience V™ (EES) N = 1152 n = 1142 99.1% n = 1139 98.9% n = 1128 98.9% n = 1137 98.7% 1 Yr Follow-up 2 Yr Follow-up 3 Yr Follow-up n = 1127 98.9% 4 Yr Follow-up n = 1135 98.5% n = 1123 98.5% 5 Yr Follow-up n = 1133 98.4%

Resolute ZES (N = 1140) Xience V EES (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 Patients1 (%) 67.0 65.6 0.51

1Complex 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).

Baseline Characteristics

Serruys PW, et al., N Engl J Med. 2010;363(2):136-46.

RESOLUTE All Comers

RESOLUTE All Comers

Resolute ZES N = 1140 patients, 1661 lesions Xience V EES N = 1152 patients, 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

Procedure Characteristics

Serruys PW, et al., N Engl J Med. 2010;363(2):136-46.

TLF (Target Lesion Failure) is defined as cardiac death, TVMI, or clinically driven TLR.

Target Lesion Failure to 5 Years

RESOLUTE All Comers

Time After Initial Procedure (years) 1 3 2 Cumulative Incidence

• f TLF (%)

10 30

16.3% 17.1%

Log rank P = 0.65 Resolute™ ZES (N = 1140) Xience V™ EES (N = 1152) Primary endpoint Pnon-inferiority <0.001

8.3% 8.2%

40 20

• No. at risk

Resolute 1140 1110 1035 992 960 920 Xience V 1152 1122 1031 995 959 926

5 4

TLR is clinically driven.

RESOLUTE All Comers

Target Lesion Failure Components at 5 Years

Resolute™ ZES (n = 1123) Xience V™ EES (n = 1133)

P = 0.48 P = 0.58 P = 1.00

DAPT Usage (%) Time After Initial Procedure (months)

RESOLUTE All Comers

DAPT* Usage over 5 Years

* Aspirin and (Clopidogrel or Ticlopidine or Prasugrel or Ticagrelor) P-value is not significant at all time points.

Resolute™ ZES (N = 1140) Xience V™ EES (N = 1152)

11.3% 12.3%

Stent Thrombosis to 5 Years: Definite

Time After Initial Procedure (years) 1 3 2 Cumulative Incidence of ARC Definite ST (%) 6

0.82% 1.62%

10 8 2 4

• No. at risk

Resolute 1140 1135 1100 1075 1049 1011 Xience V 1152 1150 1105 1084 1054 1024

4

RESOLUTE All Comers

Log rank P = 0.08 Resolute™ ZES (N = 1140) Xience V™ EES (N = 1152) 5

Very Late Stent Thrombosis: Definite

Time After Initial Procedure (years) 1 3 2 Cumulative Incidence of Very Late ARC Definite ST (%) 3

0.56% 0.47%

5 4 1 2 5 4

RESOLUTE All Comers

Log rank P = 0.76 Resolute™ ZES (N = 1140) Xience V™ EES (N = 1152)

• No. at risk

Resolute 1111 1111 1086 1060 1022 Xience V 1108 1108 1087 1057 1027

Stent Thrombosis to 5 Years: Definite / Probable

Time After Initial Procedure (years) 1 3 2 Cumulative Incidence of ARC Definite/Probable ST (%) 6

1.7% 2.4%

10 8 2 4

• No. at risk

Resolute 1140 1134 1098 1072 1044 1005 Xience V 1152 1150 1104 1083 1051 1021

5 4

RESOLUTE All Comers

Log rank P = 0.22 Resolute™ ZES (N = 1140) Xience V™ EES (N = 1152)

Very Late Stent Thrombosis: Definite / Probable

Time After Initial Procedure (years) 1 3 2 Cumulative Incidence of Very Late ARC Definite/Probable ST (%) 3

1.03% 0.84%

5 4 1 2 5 4

RESOLUTE All Comers

Log rank P = 0.66 Resolute™ ZES (N = 1140) Xience V™ EES (N = 1152)

• No. at risk

Resolute 1111 1111 1085 1057 1018 Xience V 1108 1108 1087 1055 1025

Subset N Odds Ratio 95% CI P-value Complex 1520 0.99 0.80–1.23 0.95 Small vessel (≤2.75 mm) 1308 1.01 0.79–1.28 1.00 Multi-vessel treatment 570 0.92 0.66–1.29 0.67 Diabetes 538 1.07 0.79–1.47 0.68 Bifurcations 392 1.03 0.67–1.57 1.00 Long Lesions (>18 mm) 381 0.85 0.53–1.34 0.49 STEMI 280 0.74 0.34–1.61 0.53 ISR 182 0.81 0.52–1.25 0.42

RESOLUTE All Comers

TLF Subset Analysis at 5 Years

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).

Favors R-ZES Favors EES 0.1 1.0 10.0

RESOLUTE All Comers

• The follow-up compliance at 5 years was extremely high (98.5%),

further supporting the reliability of these long term study

• utcomes 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).

Final Conclusions