3 year clinical outcomes in patients

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3 Year Clinical Outcomes in Patients with Diabetes Mellitus from the RESOLUTE US Trial

Kimberly A Skelding, MD

on behalf of the RESOLUTE US Investigators

Orlando, Florida

SCAI 2013


Author Disclosure

• Nothing to disclose


RESOLUTE US – Diabetics

• Patients with diabetes have significantly higher event rates because of:– Endothelial dysfunction– Impaired platelet function– Altered coagulation / fibrinolysis– Increased smooth muscle cell proliferation

• The ResoluteTM ZES is the only DES with an FDA approved indication for patients who have coronary artery disease and diabetes

• This post-hoc analysis reports the performance of the ResoluteTM stent in the RESOLUTE US trial in patients with diabetes

• Furthermore, these data are placed in context to the larger dataset from the RESOLUTE Pooled clinical program

Background


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) 3 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) 3 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) 1 yr

38 mm Substudy Non-RCT vs PG (R = 114)38 mm Substudy Non-RCT vs PG (R = 114) 1 yr

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

RI-US Registry Post-approval Study (R ≈ 230)Post-approval Study (R ≈ 230) Enrolling

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 1 yr

RESOLUTE Int4

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

1Meredith IT, et al. EuroIntervention. 2010;5:692-7. 2Serruys PW, et al. N Engl J Med. 2010;363:136-46. 3Silber S, et al. Lancet. 2011;377:1241-47. 4Neumann FJ, et al. EuroIntervention. 2012;7(10):1181-8. 5Yeung AC, et al. JACC. 2011;57:1778-83.


Hx ControlsPerformance Goals

ResoluteTM ZES2.25–3.5 Clinical (n=1242)

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

38mm Clinical (n=110–175)

RESOLUTE US

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


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 US – Diabetic PatientsBaseline Characteristics

%Diabetic Patients

N = 482All Patients

N = 1402

Age (yr) 64.5 ± 10.2 64.1 ± 10.7

Male 62.2 68.3

Diabetes mellitus 100.0 34.4

IDDM 28.0 9.6

Hypertension 92.9 84.2

Hyperlipidemia 95.0 87.7

Current smoker 18.0 20.9

Prior MI 21.5 21.6

Prior PCI 35.3 32.7

Prior CABG 10.8 8.8

Clinical status:

Stable angina 56.3 56.1

Unstable angina 41.5 41.9

Myocardial infarction 2.2 2.1


%Non-Diabetics

N = 920Non-IDDM

N = 347IDDM

N = 135

Age (yr) 63.9±10.9 64.9±10.3 63.5±10.1

Male 71.4 66.0 51.1

Diabetes mellitus 0.0 100.0 100.0

IDDM 0.0 0.0 100.0

Hypertension 79.6 92.2 94.8

Hyperlipidemia 83.9 95.7 93.3

Current smoker 22.4 18.4 17.0

Prior MI 21.7 20.4 24.4

Prior PCI 31.3 32.9 41.5

Prior CABG 7.8 11.0 10.4

Clinical status:

Stable angina 42.9 40.9 44.4

Unstable angina 32.3 30.5 31.9

Myocardial infarction

1.5 1.4 2.2

RESOLUTE US – Diabetic PatientsBaseline Characteristics


%

Diabetic Patientsn = 465

All Patientsn = 1402

Death (all) 5.4 4.7

Cardiac 3.0 2.1

MI (target vessel) 1.5 2.1

Q Wave 0.2 0.1

Non Q wave 1.3 1.9

Cardiac death or target vessel MI 4.3 3.9

ST Def/Prob (all) 0.0 0.3

Early (0-30 days) 0.0 0.1

Late (31-360 days) 0.0 0.1

Very late (>360 days) 0.0 0.1

TLR (clinically driven) 6.7 4.9

TVR (clinically driven) 12.5 9.7

TLF (cardiac death, TV-MI, TLR) 10.8 8.5

TVF (cardiac death, TV-MI, TVR) 15.5 12.7

RESOLUTE US – Diabetic PatientsClinical Outcomes at 36 Months


10.8

6.7

3.0

1.5

0.0

8.5

4.9

2.1 2.1

0.3

RESOLUTE US – Diabetic PatientsSafety and Efficacy Outcomes at 36 Months

Diabetic (n=465/482)

Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR. TLR is ischemia driven. Data are not prespecified or powered for the analysis shown.

Eve

nts

[%

]

All Patients (n=1341/1402)

TV-MITLR CardiacDeath

ST (ARC Def/Prob)TLF


%Non-Diabetics

N = 920Non-IDDM

N = 347IDDM

N = 135

Death (all) 4.3 3.9 9.2

Cardiac 1.6 2.7 3.8

MI (target vessel) 2.4 1.2 2.3

Q Wave 0.1 0.3 0.0

Non Q wave 2.3 0.9 2.3

Cardiac death or target vessel MI 3.7 3.6 6.1

ST Def/Prob (all) 0.5 0.0 0.0

Early (0-30 days) 0.1 0.0 0.0

Late (31-360 days) 0.1 0.0 0.0

Very late (>360 days) 0.2 0.0 0.0

TLR (clinically driven) 4.0 6.0 8.4

TVR (clinically driven) 8.2 11.4 15.3

TLF (cardiac death, TV-MI, TLR) 7.3 9.6 13.7

TVF (cardiac death, TV-MI, TVR) 11.2 13.8 19.8

RESOLUTE US – Diabetic PatientsClinical Outcomes at 36 Months

Data are not prespecified or powered for the analysis shown.


0 360 720

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TL

R

IDDMNon-IDDM

Time After Initial Procedure (days)

0%

10%

15%

20%

5%

IDDM

No. at risk 135 135 133 123 118 117 114 110 108 107

% CI 0.00 0.75 3.87 7.00 7.00 7.00 7.84 7.84 7.84 8.70

Non-IDDM

No. at risk 347 347 345 337 325 321 316 307 301 296

% CI 0.00 0.29 1.46 3.51 4.40 4.70 5.00 5.00 5.32 6.02

Non-Diabetics

No. at risk 920 918 906 894 874 861 841 820 803 798

% CI 0.22 0.66 1.21 2.09 2.54 3.00 3.58 3.82 3.94 3.94

Non-Diabetics

1080

RESOLUTE US – Diabetic PatientsCumulative Incidence of TLR at 36 Months

8.70%

3.94%

6.02%



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De

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TV

MI

IDDMNon-IDDM


0%

10%

15%

5%

IDDM

No. at risk 135 134 132 127 126 125 122 118 115 114

% CI 0.74 1.49 2.99 2.99 2.99 3.78 4.57 5.38 6.20 6.20

Non-IDDM

No. at risk 347 346 344 340 335 334 330 321 316 312

% CI 0.29 0.58 1.44 1.73 1.73 2.03 2.92 2.92 3.23 3.54

Non-Diabetics

No. at risk 920 906 897 889 876 867 848 832 819 813

% CI 1.52 1.63 1.85 1.96 2.30 2.86 3.10 3.10 3.45 3.57

Non-Diabetics

1080

RESOLUTE US – Diabetic PatientsCumulative Incidence of Cardiac Death or TVMI at 36 Months

6.20%

3.54%

3.57%



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is IDDMNon-IDDM


0%

1.5%

2.0%

1.0%

IDDM

No. at risk 135 135 134 128 127 126 123 120 117 116

% CI 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00

Non-IDDM

No. at risk 347 347 346 342 337 336 332 324 318 314

% CI 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00

Non-Diabetics

No. at risk 920 920 911 903 890 881 865 848 833 828

% CI 0.00 0.22 0.22 0.22 0.33 0.33 0.33 0.33 0.45 0.45

Non-Diabetics

0.5% 0.45%

0.0%0.0%

RESOLUTE US – Diabetic PatientsCumulative Incidence of ARC Def/Prob ST at 36 Months



RESOLUTE US & Pooled Diabetics

• In this post-hoc analysis, the RESOLUTE US trial showed very good outcomes in the diabetic subgroup, despite the higher risk nature of the diabetic patient population

• There was a low rate of TLF (10.8%) and TLR (6.7%)

• No stent thrombosis out to 3 years

Conclusions

Health & Medicine

3 year clinical outcomes in patients