for oma distribution only. © 2014 medtronic, inc. all rights reserved. 10137474doc_1a 03/14...

For OMA distribution only. © 2014 Medtronic, Inc. All rights reserved. 10137474DOC_1A 03/14

Four-Year Outcomes Following Resolute Zotarolimus-Eluting

Stent Implantation: RESOLUTE US Study

David LeeDavid Lee11, , Alan YeungAlan Yeung11, Martin Leon, Martin Leon22, Laura Mauri, Laura Mauri33

on behalf of the RESOLUTE US Investigatorson behalf of the RESOLUTE US Investigators11Stanford University School of Medicine, Stanford, CA; Stanford University School of Medicine, Stanford, CA; 22Columbia Columbia

University College of Physicians and Surgeons and University College of Physicians and Surgeons and Cardiovascular Research Foundation, New York, NY; Cardiovascular Research Foundation, New York, NY; 33Brigham Brigham

and Women’s Hospital and Harvard Medical School, Boston, MAand Women’s Hospital and Harvard Medical School, Boston, MA

ACC 2014ACC 2014


Author Disclosures Author Disclosures

Consulting Fees / Honoraria

Research / Research Grants

Ownership / Partnership / Principal

David P. Lee Medtronic, Abbott Vascular, Boston Scientific

Boston Scientific, Medtronic

Alan C. Yeung Medtronic, Cordis, Boston Scientific, Abbott Vascular

Edwards, Boston Scientific, Medtronic

Martin B. Leon Angioscore Edwards Lifesciences Apica, Claret

Laura Mauri St. Jude Medical, Biotronik Daiichi Sankyo, Boston Scientific, Sanofi-Aventis, Eli Lilly, Bristol Myers Squibb, Cordis, Medtronic, Abbott Vascular


AbstractAbstract

• Background: New-generation drug-eluting stents (DES) such as the Resolute® zotarolimus-eluting stent (R-ZES) have been shown to be safe and effective in the treatment of coronary artery disease. Long-term follow-up is necessary for clinicians to understand the risk to benefit ratio of these devices years after implantation.

• Methods: The RESOLUTE US study enrolled 1,402 patients (1,561 lesions). Patients were treated with R-ZES for de novo native coronary lesions in 1 or 2 vessels with lesion length ≤27 mm, reference vessel diameter (RVD) of 2.25–4.0 mm, and diameter stenosis ≥50% and <100%. Postprocedure dual antiplatelet therapy (DAPT) was planned for 6 months. The primary endpoint was target lesion failure (TLF; cardiac death, target vessel myocardial infarction, or clinically-driven target lesion revascularization). Follow-up is planned through 5 years.

• Results: The mean age of enrolled patients was 64.1 ± 10.7 years, 68% (n=958/1402) were male and 34% (n=482/1402) had diabetes. Follow-up was 96% (n=1341) at 3 years. DAPT use was 56.9% at 3 years (n=710/1248) TLF was 8.5% (n=114/1341) at 3 years. Academic Research Consortium definite or probable stent thrombosis was 0.3% (n=4/1341), with 2 events occurring between years 1 and 3. In patients with diabetes, TLF was 10.8% (50/465), and there were no stent thrombosis events. Outcomes through 4 years of follow-up will be presented at the 2014 American College of Cardiology Scientific Sessions.

• Conclusions: The 4-year outcomes of the RESOLUTE US study will provide clinicians with further valuable information on the long-term safety and efficacy of R-ZES.


RESOLUTE USRESOLUTE US

• New-generation drug-eluting stents such as the Resolute® zotarolimus-eluting stent (R-ZES) have been shown to be safe and effective in the treatment of coronary artery disease.

• Follow-up over several years of large and well-powered trials is critical for a reliable assessment of the long term performance of these devices.

BackgroundBackground

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RESOLUTE Global Clinical ProgramRESOLUTE 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 UpRESOLUTERESOLUTE11 Non-RCT First-in-Human (R=139)Non-RCT First-in-Human (R=139) 5 yr

RESOLUTE ACRESOLUTE AC2,32,3 1:1 RCT vs. Xience V1:1 RCT vs. Xience V™™ EES (R=1140; X=1152)EES (R=1140; X=1152) 4 yr

Non-RCT Observational (R=2349)Non-RCT Observational (R=2349) 3 yr

2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402)2.25 – 4.0 mm Non-RCT vs. Hx Control (R=1402) 4 yrRESOLUTE USRESOLUTE US66

2.5 – 3.5 mm Non-RCT (R=100) vs. Hx Control2.5 – 3.5 mm Non-RCT (R=100) vs. Hx ControlRESOLUTE JapanRESOLUTE Japan 3 yr

RESOLUTE AsiaRESOLUTE Asia77 Non-RCT Observational (R=312)Non-RCT Observational (R=312) 1 yr

RI-US RegistryRI-US Registry Post-approval study (RI≈230)Post-approval study (RI≈230) enrollingEnrolling / Planning

1:1 RCT vs. Taxus1:1 RCT vs. Taxus™™ PES (R=200; T=200)PES (R=200; T=200)R-China RCTR-China RCT88 1 yr

RESOLUTE IntRESOLUTE Int4,54,5

R-China RegistryR-China Registry99 Non-RCT Observational (R=1800)Non-RCT Observational (R=1800) 1 yr

R-Japan SVSR-Japan SVS 2.25 Non-RCT vs. PG (R=65)2.25 Non-RCT vs. PG (R=65) 2 yr

38 mm sub-study Non-RCT vs. PG (R=114)38 mm sub-study Non-RCT vs. PG (R=114) 1 yrRESOLUTE USRESOLUTE US77

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

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Hx ControlsHx ControlsPerformance GoalsPerformance Goals

Resolute stentResolute stent2.25–3.5 Clinical (n=1242)2.25–3.5 Clinical (n=1242)

2.25–3.5 Angio/IVUS (n=100)2.25–3.5 Angio/IVUS (n=100)4.0 Angio (n=60)4.0 Angio (n=60)

38mm Clinical (n=110–175)38mm Clinical (n=110–175)


PI: M. Leon, L. Mauri, A. YeungPI: M. Leon, L. Mauri, A. Yeung

Primary Endpoints: Primary Endpoints: • 2.25–3.5 Clinical → Target Lesion Failure at 12mo2.25–3.5 Clinical → Target Lesion Failure at 12mo• 2.25–3.5 Angio/IVUS → In-Stent LLL at 8mo2.25–3.5 Angio/IVUS → In-Stent LLL at 8mo• 4.0 Angio → In-Segment LLL at 8mo 4.0 Angio → In-Segment LLL at 8mo • 38 mm Clinical → Target Lesion Failure at 12mo 38 mm Clinical → Target Lesion Failure at 12mo

Drug Therapy: ASA and clopidogrel/ticlopidine ≥ 6mo (per guidelines)Drug Therapy: ASA and clopidogrel/ticlopidine ≥ 6mo (per guidelines)

De NovoDe Novo Native Coronary Lesion Native Coronary LesionVessel Diameter: 2.25 – 4.2 mmVessel Diameter: 2.25 – 4.2 mm

Lesion Length: ≤ 27 mmLesion Length: ≤ 27 mm(≤ 35 mm(≤ 35 mm lesions tx w/ 38 mm stent)lesions tx w/ 38 mm stent)

Clinical endpointsClinical endpoints

Angio/IVUS endpointsAngio/IVUS endpoints6mo6mo 4yr4yr3yr3yr2yr2yr12mo12mo 18mo18mo8mo8mo 5yr5yr9mo9mo30d30d

N = max 1577 patientsN = max 1577 patientsUp to 135 US sites Up to 135 US sites

Clinical Study DesignClinical Study Design

Mauri L, et al. Am Heart J. 2011;161:807-14.


Key Inclusion Criteria

Clinical evidence of ischemic coronary disease

Single or double de novo lesion in native coronary artery

Target lesion ≤27mm in length, diameter stenosis ≥50% <100%, and target RVD ≥2.25mm ≤4.2mm

Target vessel TIMI flow ≥2Patient is able to take DAPT for at

least 6 monthsTreatment of up to two lesions, if the

lesions are located in separate target vessels

Key Exclusion Criteria

Acute MI within 72 hours of index procedure

Previous PCI of target vessel within 9 months pre-procedure

Planned PCI of any vessel within 30 days post-procedure

Hx stroke or TIA within 6 months

LVEF <30%

RESOLUTE USRESOLUTE USKey Eligibility CriteriaKey Eligibility Criteria

Mauri L, et al. Am Heart J. 2011;161:807-14.


RESOLUTE USRESOLUTE USPatient Flow ChartPatient Flow Chart

2 YearFollow-up

4 YearFollow-up

1 YearFollow-up

n = 137498.0%

n = 1329 94.8%

n = 139099.1%

3 YearFollow-up

n = 136197.1%

Patients EnrolledPatients EnrolledN = 1402N = 1402



%%All PatientsAll Patients

(2.25 mm – 4.00 mm diameter)(2.25 mm – 4.00 mm diameter)N = 1402 Patients / 1573 LesionsN = 1402 Patients / 1573 Lesions

Age, years (mean Age, years (mean ± ± SD)SD) 64.164.1±±10.710.7

MaleMale 68.3 68.3

Diabetes mellitusDiabetes mellitus 34.4 34.4

IDDMIDDM 9.6 9.6

Prior PCIPrior PCI 32.732.7

Reason for revascularization:Reason for revascularization:

Stable anginaStable angina 56.1 56.1

Unstable anginaUnstable angina 41.9 41.9

Myocardial infarctionMyocardial infarction 2.1 2.1

LADLAD 45.9 45.9

RVD (mm)RVD (mm) 2.6 ± 0.5 2.6 ± 0.5

Type B2/C lesionType B2/C lesion 75.2 75.2

Two vessel treatmentTwo vessel treatment 10.410.4

Stents per patient (mean Stents per patient (mean ± SD)± SD) 1.2 1.2 ± ± 0.50.5

Stent length per patient (mm)Stent length per patient (mm) 22.4 22.4 ± ± 10.510.5

Baseline CharacteristicsBaseline Characteristics

Yeung AC, et al. J Am Coll Cardiol. 2011;57:1778-83.


Time After Initial Procedure (years)0 2 3 4

0Cum

ulat

ive

Inci

denc

e of

TLF

(%)

10

20

30


9.98%

No. at riskNo. at risk 14021402 13841384 13021302 12331233 11831183

% CI% CI 1.281.28 4.684.68 7.277.27 8.348.34 9.989.98

R-US All Patients (N = 1402)

Target Lesion Failure to 4 YearsTarget Lesion Failure to 4 Years

1


10.1

5.3

2.60.4

2.9

R-US All Patients (n=1329/1402)

TLR Cardiac Death

TV-MI ST (ARC Def/Prob)TLF

Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR. TLR is ischemia driven.

Even

ts (%

)RESOLUTE USRESOLUTE USSafety and Efficacy Outcomes at 4 YearsSafety and Efficacy Outcomes at 4 Years



%% n = 1329n = 1329Death (all)Death (all) 7.07.0

CardiacCardiac 2.92.9MI (target vessel)MI (target vessel) 2.62.6

Q WaveQ Wave 0.40.4Non Q waveNon Q wave 2.22.2

Cardiac death + target vessel MICardiac death + target vessel MI 5.15.1ST ARC Def/Prob (all)ST ARC Def/Prob (all) 0.40.4

Early (0-30 days)Early (0-30 days) 0.10.1Late (31-360 days)Late (31-360 days) 0.10.1Very late (>360 days)Very late (>360 days) 0.20.2

TLRTLR 5.35.3TVRTVR 10.710.7TLF (cardiac death, TV-MI, TLR)TLF (cardiac death, TV-MI, TLR) 10.110.1TVFTVF 14.714.7

Clinical Outcomes at 4 YearsClinical Outcomes at 4 Years


RESOLUTE US, AC, INTRESOLUTE US, AC, INTA

dher

ence

to D

APT

(%)

Time After Initial Procedure (months)

DAPT to 4 YearsDAPT to 4 Years

95.997.4 93.8

65.7

93.893.1

84.1

18.6

95.897.3 91.1

43.9

R-US (N=1402)

R-All Comers (N=1140)R-International (N=2349)

13.8%

34.6%

51.4%55.4

12.8

RESOLUTE All-Comers and International trials had very broad eligibility criteria and included approximately 67% complex patients. R-International trial completed follow-up at 3 yrs.


Time After Initial Procedure (years)0 2 3 4

0

1

3

5

1

RESOLUTE USRESOLUTE USDef/Prob Stent Thrombosis to 4 YearsDef/Prob Stent Thrombosis to 4 Years

0.38%Cum

ulat

ive

Inci

denc

e of

AR

C

Def

/Pro

b St

ent T

hrom

bosi

s (%

)

2

4

No. at riskNo. at risk 14021402 14021402 13551355 13081308 12621262

% CI% CI 0.000.00 0.140.14 0.220.22 0.290.29 0.380.38

R-US All Patients (N = 1402)



• Event rates remained very low out to 4 years:Event rates remained very low out to 4 years:– The rate of TLF (primary endpoint) was 10%The rate of TLF (primary endpoint) was 10%– The incidence of ARC definite or probable stent The incidence of ARC definite or probable stent

thrombosis was 0.4%thrombosis was 0.4%

• Similar to other US trials, adherence to DAPT after Similar to other US trials, adherence to DAPT after 12 months remained relatively high with 51% still 12 months remained relatively high with 51% still taking DAPT 4 years after implantation.taking DAPT 4 years after implantation.

• These late results from the RESOLUTE US study These late results from the RESOLUTE US study demonstrated excellent efficacy and safety and demonstrated excellent efficacy and safety and support the long term performance of the Resolute support the long term performance of the Resolute stent.stent.

ConclusionsConclusions

for oma distribution only. © 2014 medtronic, inc. all rights reserved. 10137474doc_1a 03/14...

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