2 Year Clinical Outcomes from the Pivotal RESOLUTE US Study Laura Mauri MD, MSc on behalf of the RESOLUTE US Investigators Brigham and Women’s Hospital

2 Year Clinical Outcomes from the Pivotal RESOLUTE US Study

Laura Mauri MD, MScon behalf of the RESOLUTE US

Investigators

Brigham and Women’s HospitalBoston, MA

ACC 2012

Enrollment Complete - In Follow Up

RESOLUTE1 Non-RCT First-in-Human (R=139)Non-RCT First-in-Human (R=139) 5 yr

RESOLUTE AC2,3 1:1 RCT vs. Xience V (R=1140; X=1152)1:1 RCT vs. Xience V (R=1140; X=1152) 2 yr

Non-RCT Observational (R=2349)Non-RCT Observational (R=2349) 2 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) 2 yrRESOLUTE US5

2.5 – 3.5 mm Non-RCT (R=100) vs. Hx Control2.5 – 3.5 mm Non-RCT (R=100) vs. Hx ControlRESOLUTE Japan 2 yr

R Japan SVS 2.25 Non-RCT vs. PG (R=65)2.25 Non-RCT vs. PG (R=65) < 1yr

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

RESOLUTE Asia Non-RCT Observational (R=312)Non-RCT Observational (R=312) < 1yr

RI-US Registry Post-approval study (R=230)Post-approval study (R=230) plan

RESOLUTE US

RESOLUTE Global Clinical Program

Enrolling / Planning

1:1 RCT vs. Taxus (R=200; T=200)1:1 RCT vs. Taxus (R=200; T=200)R-China RCT < 1yr

RESOLUTE Int4

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 Yeung AC, et al. JACC. 2011;57:1778-83.

R-China Registry Non-RCT Observational (R=1800)Non-RCT Observational (R=1800) < 1yr

Hx ControlsPerformance Goals

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

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

38mm Clinical (n=110–175)

RESOLUTE US

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

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

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

De Novo Native Coronary LesionVessel Diameter: 2.25 – 4.2 mm

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

Clinical endpoints

Angio/IVUS endpoints

6mo 4yr3yr2yr12mo 18mo8mo 5yr9mo30d

N = max 1577 patientsUp to 135 US sites

Clinical 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 ≥2

Patient is able to take DAPT for at least 6 months

Treatment 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 USKey Eligibility Criteria

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

RESOLUTE USPatient Flow Chart

1Yr Clinical Follow-upn = 1386

98.9%


98.9%

Patients EnrolledN = 1402

Patients EnrolledN = 1402


96.9%


96.9%

RESOLUTE US

%All Patients

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

Age, years (mean ± SD) 64.1±10.7

Male 68.3

Diabetes mellitus 34.4

IDDM 9.6

Prior PCI 32.7

Reason for revascularization:

Stable angina 56.1

Unstable angina 41.9

Myocardial infarction 2.1

LAD 45.9

RVD (mm) 2.6 ± 0.5

Type B2/C lesion 75.2

Two vessel treatment 10.4

Stents per patient (mean ± SD) 1.2 ± 0.5

Stent length per patient (mm) 22.4 ± 10.5

Baseline Characteristics

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

25

15

10

5

0

0 90 180 360 450 540 630 720

Cu

mu

lati

ve I

nci

de

nce

of

TL

F (

%)

Time After Initial Procedure (Days)

RESOLUTE US (N=1402)

RESOLUTE US – All PatientsTarget Lesion Failure to 24 Months

Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

20

270

7.3%

RESOLUTE All Comers (N=1140)

RESOLUTE International (N=2349)

11.2%9.8%

RESOLUTE US – All PatientsSafety and Efficacy Outcomes at 24 Months

Resolute ZES (n=1359/1402)

TLR Cardiac Death

TV-MIST

(ARC Def/Prob)TLF

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

Eve

nts

[%

]

99/1359 58/1359 20/1359 3/135926/1359

RESOLUTE US – All Patients

%12M

n = 138624M

n = 1359

Death (all) 1.3 3.0

Cardiac 0.6 1.5

MI (target vessel) 1.3 1.9

Q Wave 0.1 0.1

Non Q wave 1.2 1.8

Cardiac death + target vessel MI 1.9 3.2

ST Def/Prob (all) 0.1 0.2

Early (0-30 days) 0.1 0.1

Late (31-360 days) 0.1 0.1

Very late (>360 days) -- 0.1

TLR 2.8 4.3

TVR 4.5 7.6

TLF (cardiac death, TV-MI, TLR) 4.6 7.3

TVF 6.1 10.1

Clinical Outcomes at 12 and 24 Months

30 180 360 540 7200

10

20

30

40

50

60

70

80

90

100

DAPT to 24 MonthsA

dh

eren

ce

to D

AP

T (

%)

Time After Initial Procedure (days)

RESOLUTE US, All Comers, International Trials

95.597.1 93.5

73.8

67.2%

93.8 93.1

84.1

18.6%

95.897.391.1

43.9%

R-US (N=1402)

R-AC (N=1140)R-INT (N=2349)

Def/prob Stent Thrombosis to 24 MonthsRESOLUTE US, All Comers, International Trials

Error bars indicate a point-wise two-sided 95% confidence interval (±1.96*SE). Standard Error based on the Greenwood Formula.

25

15

10

5

00 90 180 270 360 720

Time After Initial Procedure (days)

20

630540450

1.9%1.0%

RESOLUTE All Comers (N=1140)

RESOLUTE International (N=2349)

RESOLUTE US (N=1402)

0.2%

% (n)30 Daysn=1399

1 Yearn=1386

2 Year n=1359

Stent thrombosis (ARC def/prob)

0.1 (1) 0.1 (2) 0.2 (3)

Early (< 30 days) 0.1 (1) 0.1 (1) 0.1 (1)

Late (30-360 days) n/a 0.1 (1) 0.1 (1)

Very Late (>360 days) n/a n/a 0.1 (1)

RESOLUTE US – All PatientsStent Thrombosis at 24 Months

RESOLUTE US Main Study (2.5-3.5mm single lesion)

Safety and Efficacy Outcomes at 24 Months


TLRCardiac Death TV-MI

ST (ARC Def/Prob)TLF

Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR (ischemia driven). TLF rate at 2 years for Endeavor ZES was 8.1% (Post-hoc analysis, Pnoninferiority<0.001)

Eve

nts

[%

]

57/968 10/968 17/968 1/96833/968

RESOLUTE US – 2.25mm Cohort Safety and Efficacy Outcomes at 24 Months





Eve

nts

[%

]

12/147 5/147 2/147 2/1477/147

RESOLUTE US – Diabetic PatientsSafety and Efficacy Outcomes at 24 Months





Eve

nts

[%

]

42/474 10/474 7/474 0/47427/474

RESOLUTE US – Diabetic PatientsSafety and Efficacy Outcomes at 24 Months

Diabetic (n=474/482)




Eve

nts

[%

]

57/885 10/885 19/885 3/88531/885

Non-Diabetic (n=885/920)

42/474 10/474 7/474 0/47427/474

RESOLUTE US

• Out to 2 years, the TLF (primary endpoint) was consistently low in all groups studied– All patients 7.3%, main cohort (2.5-3.5 single

lesion) 5.9%, small vessels (2.25 mm) 8.2%

• Stent thrombosis was very low (0.2%) with only 1 new ST event after 1 year, indicating a favorable safety profile

• Very good outcomes in the diabetic subgroup – Low rate of TLF (8.9%) and TLR (5.7%)– No stent thrombosis out to 2 years

Conclusions

Documents

2 Year Clinical Outcomes from the Pivotal RESOLUTE US Study Laura Mauri MD, MSc on behalf of the RESOLUTE US Investigators Brigham and Women’s Hospital