7-Year Follow-up From a Randomized Trial of Sirolimus-Eluting vs. - - PowerPoint PPT Presentation

7-Year Follow-up From a Randomized Trial

• f Sirolimus-Eluting vs. Everolimus-Eluting Stents

in Patients With Coronary Artery Disease (RESET)

Hiroki Shiomi, MD

Kyoto University Graduate School of Medicine

Ken Kozuma, MD; Takeshi Morimoto, MD, MPH; Kazushige Kadota, MD; Kengo Tanabe, MD; Yoshihiro Morino, MD; Takashi Akasaka, MD; Mitsuru Abe, MD; Yasuaki Takeji MD; Satoru Suwa, MD; Yoshiaki Ito, MD; Masakazu Kobayashi, MD; Kazuoki Dai, MD; Koichi Nakao, MD; Yasuhiro Tarutani, MD; Takeshi Kimura, MD;

On behalf of the RESET Investigators

I, Hiroki Shiomi or my spouse/partner have had a financial interest/ arrangement or affiliation with the organization(s) listed below.

Disclosure Statement of Financial Interest

• Grant/Research Support
• Consulting Fees/Honoraria
• Major Stock Shareholder/Equity
• Royalty Income
• Ownership/Founder
• Intellectual Property Rights
• Other Financial Benefit
• Abbott Vascular
• None
• None
• None
• None
• None
• None

Affiliation/Financial Relationship Company

Background

 Late adverse events beyond 1-year, such as VLST and late TLR, were reported to continue occurring for at least 5-7 years after first-generation DES implantation.

Kimura T, et al. Circulation. 2012 Jan 31;125(4):584-91.

RESET Trial

(Randomized Evaluation of Sirolimus-eluting versus Everolimus-eluting stent Trial)

Study Design Patient Flow Chart

Shiomi H, et al. Circ Cardiovasc Interv 2014;7:343-54.

(From Feb. to July, 2010)

 Non-inferiority of EES relative to SES for the primary efficacy (TLR) and safety (Death/MI) endpoints  Lack of very long-term data beyond 5-year comparing new-generation versus first-generation DES.

Summary for RESET 3-Year Results

Target Lesion Revascularization Death or Myocardial Infarction Shiomi H, et al. Circ Cardiovasc Interv 2014;7:343-54.

RESET 7-year Follow-up: Patients Flow Chart

EES

(N=1335)

SES

(N=1332)

P Value Age – years 69.2±9.7 69.4±9.6 0.64 Male gender 1029 (77%) 1012 (76%) 0.50 Hypertension 1068 (80%) 1076 (81%) 0.61 Diabetes mellitus 599 (45%) 589 (44%) 0.74 ESRD (eGFR<30) not on hemodialysis 30 (2.3%) 37 (2.8%) 0.38 Hemodialysis 73 (5.5%) 67 (5.0%) 0.61 Prior myocardial infarction 398 (30%) 401 (30%) 0.87 Prior Stroke 143 (11%) 131 (9.8%) 0.46 Heart failure 173 (13%) 181 (14%) 0.63

Baseline Characteristics

EES

(N=1335)

SES

(N=1332)

P Value Clinical presentation 0.06 Stable coronary artery disease 1090 (82%) 1075 (81%) Unstable angina 147 (11%) 179 (13%) Acute myocardial infarction 98 (7.3%) 78 (5.9%) SYNTAX score (median) 10 (6-16) 9 (6-15) 0.32

• No. of treated lesions per patient

1.24±0.52 1.23±0.49 0.43

• No. of stents used

1.51±0.77 1.48±0.73 0.25 Total stent length (mm) 30.8±18.6 31.2±18.8 0.54 Multivessel treatment 156/1335 (12%) 135/1332 (10%) 0.20 IVUS use - no./total no. (%) 1215/1505 (81%) 1217/1498 (81%) 0.72

Baseline Characteristics

Persistent Discontinuation of DAPT

Interval 0 day 30 days 1 year 3 years 5 years 7 years EES group Cumulative incidence (N of pts with event) 1.3% 14.5% 40.5% 55.5% 66.0% N of patients at risk 1335 1317 1124 724 486 343 SES group Cumulative incidence (N of pts with event) 1.1% 16.1% 42.0% 55.5% 65.8% N of patients at risk 1332 1316 1098 708 489 344

Primary Efficacy Endpoint:

Target Lesion Revascularization (TLR)

Interval 0 day 30 days 1 year 3 years 5 years 7 years EES group Cumulative incidence (N of pts with event) 0.3% (4) 4.3% (57) 6.7% (87) 8.4% (107) 10.2% (126) N of patients at risk 1335 1329 1252 1143 1012 918 SES group Cumulative incidence (N of pts with event) 0.4% (5) 4.7% (61) 7.4% (96) 9.5% (120) 11.7% (143) N of patients at risk 1332 1323 1237 1127 988 868

TLR events adjudicated by the angiographic core laboratory: 230/269 (86%).

Landmark Analysis at 1-year: TLR

Interval 0 day 1 year 3 years 5 years 7 years EES group Cumulative incidence (N of pts with event) 4.3% (57) 2.5% (30) 4.3% (50) 6.2% (69) N of patients at risk 1335 1252 1143 1012 918 SES group Cumulative incidence (N of pts with event) 4.7% (61) 2.9% (35) 5.1% (59) 7.4% (82) N of patients at risk 1332 1237 1127 988 868

Primary Safety Endpoint:

Death or Myocardial Infarction

Death or MI Landmark analysis at 1-year

Definite ST Definite/Probable ST

Stent Thrombosis

Composite Endpoints

Target-Lesion Failure

Cardiac death, Target-vessel MI, or Clinically-driven TLR

Target-Vessel Failure

Cardiac death, MI, or Clinically-driven TVR

Clinical Endpoints

EES (N=1335) SES (N=1332)

• N. of patients with events

(Cumulative incidence)

• N. of patients with events

(Cumulative incidence) Univariate HR (95% CI) P Value Death 214(16.8%) 234(18.5%) 0.90(0.75-1.08) 0.27 Cardiac death 72(6.0%) 86(7.2%) 0.82(0.60-1.13) 0.23 Myocardial infarction 76(6.2%) 87(7.0%) 0.86(0.63-1.16) 0.32 Stroke 69(5.7%) 63(5.3%) 1.09(0.77-1.53) 0.63 Major Bleeding -TIMI minor/major 91(7.4%) 124(10.2%) 0.72(0.55-0.95) 0.02

• GUSTO moderate/severe

89(7.2%) 115(9.4%) 0.76(0.58-1.01) 0.055 TVR 204(16.6%) 201(16.7%) 1.01(0.83-1.22) 0.96 Coronary-artery bypass grafting 21(1.8%) 34(2.9%) 0.61(0.35-1.04) 0.07 Any coronary revascularization 376(30.5%) 368(30.2%) 1.01(0.88-1.17) 0.87

Subgroup Analysis for the Primary Endpoint of TLR EES versus SES

Summary

 No differences in 7-year risk for TLR and ST between new-generation EES and first-generation SES.  No clear advantage of new-generation EES over first-generation SES for late adverse events such as VLST and late TLR.  Better clinical outcomes with EES relative to SES for the composite secondary endpoints such as TLF and TVF.

Limitations

 Loss of substantial number of patients from some of the participating centers for the extended study, though the randomized scheme was basically maintained  No power calculation for TLR in the extended follow-up study  Apparent lack of power for stent thrombosis  Dominance of lower risk patients with stable CAD or with low SYNTAX score  First-generation SES currently not available for clinical use, though there are a large number of patients who had already received first-generation SES

Conclusions

During 7 years of follow-up, the risk for TLR was not significantly different between new-generation EES and first-generation SES.