trademarks may be registered and are the property of their respective owners. © 2012 medtronic,...

Trademarks may be registered and are the property of their respective owners. © 2012 Medtronic, Inc. All rights reserved. UC201303039EN 10/2012

The Diabetic Patient and The Diabetic Patient and Drug Eluting StentsDrug Eluting Stents

<SPEAKER Name><SPEAKER Name>


Resolute IntegrityIntegrity™™ DES DES

Established Components

• Integrity™ cobalt alloy stentIntegrity™ cobalt alloy stent

• MicroTrac™ delivery systemMicroTrac™ delivery system

• Zotarolimus antiproliferative drug Zotarolimus antiproliferative drug

Unique Polymer TechnologyUnique Polymer Technology

• BioLinx™ polymer is a unique blend of three BioLinx™ polymer is a unique blend of three polymers to control drug release, support polymers to control drug release, support biocompatibility and enhance elution ratebiocompatibility and enhance elution rate

• Drug-release kinetics: complete elution Drug-release kinetics: complete elution by 180 days by 180 days

100

80

60

40

20

0

Zo

taro

lim

us

Re

lea

se

(%

)

0 50 100 150 200

Days

% eluted

System ComponentsSystem Components

Udipi K, et al. EuroIntervention. 2007; 3:137-9Meredith IT, et al. J Am Coll Cardiol Intv. 2009; 2:977-85Meredith IT, et al. EuroIntervention. 2007; 3:50-53


RESOLUTERESOLUTE 139139

RESOLUTE ACRESOLUTE AC 11401140

RESOLUTE IntRESOLUTE Int 23492349

RESOLUTE USRESOLUTE US 14021402

RESOLUTE JapanRESOLUTE Japan 100100

5130 Resolute™ DES population5130 Resolute™ DES population5130 Resolute™ DES population5130 Resolute™ DES population

Matched cohort diabetic populationMatched cohort diabetic populationN = 878 (standard risk)N = 878 (standard risk)

Matched cohort is all enrolled diabetic subjects excluding subjects with bifurcation, saphenous vein graft (SVG), ISR, AMI (≤72 hours), left ventricular ejection fraction (LVEF) <30%, an unprotected left main lesion, ≥3 vessels, renal impairment (creatinine ≥ 140µmol/L), total lesion length per vessel >27 mm, ≥2 lesions per vessel, lesion with thrombus, or lesion with total occlusion.

Matched cohort is all enrolled diabetic subjects excluding subjects with bifurcation, saphenous vein graft (SVG), ISR, AMI (≤72 hours), left ventricular ejection fraction (LVEF) <30%, an unprotected left main lesion, ≥3 vessels, renal impairment (creatinine ≥ 140µmol/L), total lesion length per vessel >27 mm, ≥2 lesions per vessel, lesion with thrombus, or lesion with total occlusion.

Diabetic Patient PopulationsDiabetic Patient Populations

RESOLUTE Pooled Diabetic AnalysisRESOLUTE Pooled Diabetic Analysis

Total diabetic patient populationTotal diabetic patient populationN = 1535N = 1535

Standard risk patient cohort pre-specified for FDA indication



Prespecified analysis designed with FDA for indication to treat patients with diabetes. Resolute™ DES matched cohort was compared against Resolute™ DES matched cohort was compared against

prespecified performance goal based on DES meta-analysis.prespecified performance goal based on DES meta-analysis.

FDA Approved IndicationFDA Approved Indication

Performance Goal* Resolute DES†

Target vessel failure (TVF) is defined as cardiac death, target vessel myocardial infarction, and clinically driven target vessel revascularization (TVR)*Performance goal based on DES trials meta-analysis: DIABETES, RAVEL DM, SIRIUS DM, TAXUS IV, SCORPIUS, ENDEAVOR Pooled DM †RESOLUTE matched cohort diabetes pooled analysis (N = 878).

Target Vessel Failure at 12 MonthsTarget Vessel Failure at 12 Months(powered endpoint)(powered endpoint)

Target Vessel Failure at 12 MonthsTarget Vessel Failure at 12 Months(powered endpoint)(powered endpoint)

14.5

7.8

PP = 0.001 = 0.001

Eve

nts

(%

)


Why is Medtronic interested in Why is Medtronic interested in Diabetes as a high risk group for Diabetes as a high risk group for

patients undergoing PCI?patients undergoing PCI?


The Prevalence of Diabetes Keeps The Prevalence of Diabetes Keeps Increasing… Increasing…

Diabetes currently affects 25.8 million people in the United StatesDiabetes currently affects 25.8 million people in the United States22Diabetes currently affects 25.8 million people in the United StatesDiabetes currently affects 25.8 million people in the United States22

1. Maps of Diabetes and Obesity in 1994, 2000, and 2009. Centers for Disease Control and Prevention Web site. http://www.cdc.gov/diabetes/statistics/slides/maps_diabetesobesity94.pdf. Accessed 10/13/11.

2. National Diabetes Statistics, 2011. National Diabetes Information Clearinghouse Web site. http://www.diabetes.niddk.nih.gov/dm/pubs/statistics/#fast. Accessed 11/28/11.

19941

20001

20091

No data <4.5% 4.5%-5.9% 6.0%-7.4% 7.5%-8.9% ≥9.0%


……and Is Estimated to Still Beand Is Estimated to Still Be on the Rise on the Rise

Year

US

Po

pu

lati

on

, %

By 2020, it is projected that 39 million people will have diabetes By 2020, it is projected that 39 million people will have diabetes and 96 million people will have prediabetes in the United Statesand 96 million people will have prediabetes in the United StatesBy 2020, it is projected that 39 million people will have diabetes By 2020, it is projected that 39 million people will have diabetes and 96 million people will have prediabetes in the United Statesand 96 million people will have prediabetes in the United States

The United States of diabetes: challenges and opportunities in the decade ahead. http://www.unitedhealthgroup.com/hrm/UNH_ WorkingPaper5.pdf. UnitedHealth Center for Health Reform & Modernization working paper 5. Published November 2010. Accessed 11/28/11.


The Risk of Adverse Events Increases in The Risk of Adverse Events Increases in Patients With Both CVD and DiabetesPatients With Both CVD and Diabetes

• Circulatory disorders associated with diabetes include coronary heart Circulatory disorders associated with diabetes include coronary heart disease, stroke, disease, stroke, peripheral arterial diseaseperipheral arterial disease, cardiomyopathy, and , cardiomyopathy, and congestive heart failurecongestive heart failure11

– Even in the absence of CVD, both the ADA and the AHA identify diabetes as a Even in the absence of CVD, both the ADA and the AHA identify diabetes as a high risk condition for macrovascular CVDhigh risk condition for macrovascular CVD2,32,3

• CVD is a major complication of diabetes and the leading cause of early CVD is a major complication of diabetes and the leading cause of early deathdeath44

– About 65% of people with diabetes die from heart disease or strokeAbout 65% of people with diabetes die from heart disease or stroke

• Adults with diabetes are 2-4 times more likely to have heart disease or a Adults with diabetes are 2-4 times more likely to have heart disease or a stroke than those without diabetesstroke than those without diabetes44

• High blood glucose in adults with diabetes increases the risk of High blood glucose in adults with diabetes increases the risk of myocardial infarction, angina, stroke, and coronary artery diseasemyocardial infarction, angina, stroke, and coronary artery disease55

• People with type 2 diabetes also have high rates of hypertension, high People with type 2 diabetes also have high rates of hypertension, high cholesterol, and obesitycholesterol, and obesity66

ADA=American Diabetes Association; AHA=American Heart Association; CVD=cardiovascular disease.1 Buse J, et al. Diabetes Care. 2007;30:162-172. 2 Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-2497. 3 American Diabetes Association. Diabetes Care. 2011;(suppl 1):S11-S61. 4 The Link Between Diabetes and Cardiovascular Disease. National Diabetes Education Program Web site. http://ndep.nih.gov/media/CVD_FactSheet.pdf. Accessed 11/28/11.5 Nathan D, et al. N Engl J Med. 2005;353:2643-2653. 6 National Diabetes Statistics, 2011. National Diabetes Information Clearinghouse Web site. http://www.diabetes.niddk.nih.gov/dm/pubs/statistics/#fast. Accessed 11/28/11.


CVD and CHD Mortality Rates Are CVD and CHD Mortality Rates Are Significantly Higher in Adults With Diabetes Significantly Higher in Adults With Diabetes

N = 6255N = 6255Mean follow-up, 13.3 yearsMean follow-up, 13.3 years

N = 6255N = 6255Mean follow-up, 13.3 yearsMean follow-up, 13.3 years

Mortality Rates in US Adults With vs Without Diabetes and/or Preexisting CVD

Dea

ths

per

100

0 P

erso

n-Y

ears

a

aAdjusted by age and gender.CHD = coronary heart disease; CVD = cardiovascular disease.Adapted from Malik S, et al. Circulation. 2004;110:1245-1250.


Complications of Diabetes and CVD Account for Complications of Diabetes and CVD Account for Almost Half of Top Diagnoses for Health ExpensesAlmost Half of Top Diagnoses for Health Expenses

The 16 Leading Diagnoses for Direct Health Expenditures: United States, 2007

Billions of Dollars

Unrelated to CVD/diabetes

Related to CVD/diabetes

COPD = chronic obstructive pulmonary disease; CVD = cardiovascular disease.Roger V, et al. Circulation. 2011;123:e18-e209.


~30% of PCIs are in ~30% of PCIs are in Patients with DiabetesPatients with Diabetes

PCI=percutaneous coronary intervention.Aronson D and Edelman ER. (2010) Revascularization for Coronary Artery Disease in Diabetes Mellitus: Angioplasty, Stents and Coronary Artery Bypass Grafting. Rev. Endocr. Metab. Disord. 11:75-86


Patients with Diabetes Have Poorer Patients with Diabetes Have Poorer Outcomes Post PCIOutcomes Post PCI

Compared with patients without diabetes, patients Compared with patients without diabetes, patients with diabetes experience:with diabetes experience:•Twice the early mortality associated with acute Twice the early mortality associated with acute coronary syndromecoronary syndrome•Higher rate of reinfarctionHigher rate of reinfarction•Higher likelihood of myocardial infarction in first year Higher likelihood of myocardial infarction in first year post PCIpost PCI•More procedural complicationsMore procedural complications•Longer ICU and hospital staysLonger ICU and hospital stays•Increased interactions with hypoglycemic medicationsIncreased interactions with hypoglycemic medications•Higher rates of restenosis, target lesion Higher rates of restenosis, target lesion revascularization, and target vessel revascularizationrevascularization, and target vessel revascularization

ICU=intensive care unit; PCI=percutaneous coronary intervention.Nesto R, et al. Presented at TCT 2003. Rutter MK, Nesto RW. Heart. 2010 Sep;96(18):1436-40.Coronary revascularisation in the patient with diabetes: balancing risk and benefit.


What Mechanisms Underlie Poorer What Mechanisms Underlie Poorer Outcomes in Diabetics after PCI?Outcomes in Diabetics after PCI?

• Platelet and endothelial dysfunction resulting in Platelet and endothelial dysfunction resulting in accelerated atherosclerosis and plaque accelerated atherosclerosis and plaque instabilityinstability

• Plaques from diabetic patients removed by Plaques from diabetic patients removed by coronary atherectomy have greater lipid deposits coronary atherectomy have greater lipid deposits and numbers of macrophagesand numbers of macrophages

• Endothelial dysfunction is thought to induce Endothelial dysfunction is thought to induce negative arterial remodeling in response to negative arterial remodeling in response to atherosclerosis resulting in a decrease in luminal atherosclerosis resulting in a decrease in luminal sizesize

Roffi, M et al. Current concepts on revascularization in diabetic patients. Eur Heart Journal. 2011. 32:2748-2757. Moreno PR et al. Coronary composition and macrophage infiltration in atherectomy specimens from patients with diabetes mellitus. Circulation. 2000 Oct 31;102(18):2180-4.


QuestionsQuestions

• How often is the diabetic status of a How often is the diabetic status of a patient known prior to PCI?patient known prior to PCI?

• How often do you know if the patient How often do you know if the patient is NIDDM or IDDM?is NIDDM or IDDM?

• Would this affect your treatment Would this affect your treatment strategy?strategy?

(N)IDDM = (non) Insulin-Dependent Diabetes Mellitus


How are Drug Eluting Stents How are Drug Eluting Stents Performing in Diabetic Patients?Performing in Diabetic Patients?


DES Results in More Overt Benefits vs DES Results in More Overt Benefits vs BMS in Patients Without DiabetesBMS in Patients Without Diabetes

Pat

ien

ts, %

P < 0.001

P = 0.31 P < 0.001P = 0.22

P = 0.13

Pat

ien

ts, %

P < 0.001 P < 0.001

P < 0.001

Outcomes at 4 Years in PatientsWithout Diabetes (n = 2751)

Outcomes at 4 Years in PatientsWith Diabetes (n = 1826)

BMS=bare-metal stent; DES=drug-eluting stent; MACE=major adverse cardiac event; MI=myocardial infarction; TVR=target vessel revascularization. All stents implanted between 4/2004-12/2008.Minha S, et al. Catheter Cardiovasc Interv. 2011;78:710-717.


SYNTAX Diabetic Subgroup Analysis: SYNTAX Diabetic Subgroup Analysis: Impact of Diabetes on CABG and Stenting Outcomes Impact of Diabetes on CABG and Stenting Outcomes – Study Design– Study Design

• Aspirin recommended indefinitely; thienopyridine for Aspirin recommended indefinitely; thienopyridine for ≥6 months≥6 months

1800 patients with left main disease and/or1800 patients with left main disease and/or1-, 2-, or 3-vessel disease1-, 2-, or 3-vessel disease

1800 patients with left main disease and/or1800 patients with left main disease and/or1-, 2-, or 3-vessel disease1-, 2-, or 3-vessel disease

Stratified by the presence or absence of medically treated diabetesStratified by the presence or absence of medically treated diabetesand left main diseaseand left main disease

Stratified by the presence or absence of medically treated diabetesStratified by the presence or absence of medically treated diabetesand left main diseaseand left main disease

Diabetes Diabetes (n = 452)(n = 452)Diabetes Diabetes (n = 452)(n = 452)

No diabetes No diabetes (n = 1348)(n = 1348)

No diabetes No diabetes (n = 1348)(n = 1348)

CABGCABG(n = 676)(n = 676)CABGCABG

(n = 676)(n = 676)TAXUSTAXUS® ® DES DES

(n = 672)(n = 672)TAXUSTAXUS® ® DES DES

(n = 672)(n = 672)CABGCABG

(n = 221)(n = 221)CABGCABG

(n = 221)(n = 221)TAXUSTAXUS ® ® DES DES

(n = 231)(n = 231)TAXUSTAXUS ® ® DES DES

(n = 231)(n = 231)

CABG = coronary artery bypass graft.Mack M, et al. Ann Thorac Surg. 2011 Dec;92(6):2140-6.


SYNTAX Diabetic Subgroup Analysis: SYNTAX Diabetic Subgroup Analysis: Diabetes Increased Adverse Outcomes More in Patients Diabetes Increased Adverse Outcomes More in Patients Receiving TAXUSReceiving TAXUS® ® DES vs CABGDES vs CABG

Outcomes at 3 Years in Patients With vs Without Diabetes

P = 0.633

P < 0.001

P = 0.505

P = 0.102

P < 0.001

P = 0.345P = 0.087

P < 0.001

Pa

tie

nts

, %

CABG = coronary artery bypass graft.Mack M, et al. Ann Thorac Surg. Dec;92(6):2140-6.


ENDEAVOR IV Diabetic Analysis: ENDEAVOR IV Diabetic Analysis: Impact of Diabetes on Treatment With EndeavorImpact of Diabetes on Treatment With Endeavor®® ZES vs ZES vs TAXUSTAXUS®® PES in Patients With Diabetes – Study Design PES in Patients With Diabetes – Study Design

• Primary endpoint was the rate of target vessel failure, a composite of cardiac Primary endpoint was the rate of target vessel failure, a composite of cardiac death, myocardial infarction, or clinically driven target vessel revascularizationdeath, myocardial infarction, or clinically driven target vessel revascularization

• Drug therapy: aspirin and clopidogrel/ticlopidine for ≥6 monthsDrug therapy: aspirin and clopidogrel/ticlopidine for ≥6 months

1548 patients with single de novo native 1548 patients with single de novo native coronary artery lesionscoronary artery lesions

RVD, ≥2.5-≤3.5 mm; lesion length, ≤27 mmRVD, ≥2.5-≤3.5 mm; lesion length, ≤27 mm

1548 patients with single de novo native 1548 patients with single de novo native coronary artery lesionscoronary artery lesions

RVD, ≥2.5-≤3.5 mm; lesion length, ≤27 mmRVD, ≥2.5-≤3.5 mm; lesion length, ≤27 mm

80 US sites80 US sitesStratified by diabetic status and clinical siteStratified by diabetic status and clinical site

80 US sites80 US sitesStratified by diabetic status and clinical siteStratified by diabetic status and clinical site

No diabetesNo diabetes(n = 1071)(n = 1071)

No diabetesNo diabetes(n = 1071)(n = 1071)

DiabetesDiabetes(n = 477)(n = 477)DiabetesDiabetes(n = 477)(n = 477)

Endeavor ZES (n = 241)


TAXUS PESTAXUS PES(n = 236)(n = 236)






PES = paclitaxel-eluting stent; RVD = reference vessel diameter; ZES = zotarolimus-eluting stent.Kirtane A, et al. JACC Cardiovasc Interv. 2009;2:967-976.


ENDEAVOR IV Diabetic Analysis: ENDEAVOR IV Diabetic Analysis: Similar Outcomes at 1-Year in Patients With Diabetes Similar Outcomes at 1-Year in Patients With Diabetes Treated With E-ZES or PESTreated With E-ZES or PES

P = 0.24P = 0.24

P = 1.00P = 0.45

P = 0.19

P = 0.70

P = 0.87P = 0.53

P = 0.89P = 0.43

P = 0.62

P = 0.06

Outcomes and Major Adverse Events at 1 Year in Patients With vs Without Diabetes

Inci

den

ce, %

PES = paclitaxel-eluting stent; ST = stent thrombosis; TLR = target lesion revascularization; TVF = target vessel failure; TVR = target vessel revascularization; E-ZES = Endeavor zotarolimus-eluting stent.Kirtane A, et al. JACC Cardiovasc Interv. 2009;2:967-976.


SPIRIT/COMPARE Pooled Diabetic Analysis: SPIRIT/COMPARE Pooled Diabetic Analysis: Impact of Diabetes on Treatment With EES vs PES Impact of Diabetes on Treatment With EES vs PES – Overview of Study Designs– Overview of Study Designs

SPIRIT IISPIRIT II SPIRIT IIISPIRIT III SPIRIT IVSPIRIT IV COMPARECOMPARE

Sites, n Sites, n (location)(location)

28 28 (EU, India, NZ)(EU, India, NZ)

65 65 (United States)(United States)

66 66 (United States)(United States)

1 1 (Netherlands)(Netherlands)

Intent-to-treat Intent-to-treat patients, npatients, n 300300 10021002 36873687 18001800

Patients with Patients with diabetes, n (%)diabetes, n (%) 69 (23.1)69 (23.1) 290 (29.0)290 (29.0) 1195 (32.4)1195 (32.4) 325 (18.1)325 (18.1)

EES:PESEES:PES 3:13:1 2:12:1 2:12:1 1:11:1

PES platformPES platform TAXUSTAXUS®® Express Express®® TAXUS LibertéTAXUS Liberté®®

Primary endpointsPrimary endpoints In-stent LL at In-stent LL at 6 months6 months

In-stent LL at In-stent LL at 6 months; TVF 6 months; TVF

at 9 monthsat 9 months

TLR at TLR at 12 months12 months

MACE at MACE at 12 months12 months

RVD, mmRVD, mm 2.5-4.252.5-4.25 2.5-3.752.5-3.75 2.5-3.752.5-3.75 Not specifiedNot specified

Lesion length, mmLesion length, mm ≤≤2828 No limitNo limit

EES = everolimus-eluting stent; EU = Europe; LL = late loss; MACE = major adverse cardiac event; NZ = New Zealand; PES = paclitaxel-eluting stent; RVD = reference vessel diameter; TLR = target lesion revascularization; TVF = target vessel failure.Stone G, et al. Circulation. 2011;124:893-900.


SPIRIT/COMPARE Pooled Diabetic Analysis: SPIRIT/COMPARE Pooled Diabetic Analysis: Patients Without Diabetes Treated With EES vs PES Patients Without Diabetes Treated With EES vs PES Had Significantly Reduced OutcomesHad Significantly Reduced Outcomes

EES vs PES: 2-Year Event Rates in Patients With vs Without Diabetes

P < 0.0001

P = 0.88P = 0.49

P = 0.10

P < 0.0001P = 0.60

P = 0.50

P = 0.86

P < 0.0001

P < 0.0001

Pat

ien

ts,

%

EES = everolimus-eluting stent; MACE = major adverse cardiac event; PES = paclitaxel-eluting stent; ST = stent thrombosis.Stone G, et al. Circulation. 2011;124:893-900.


How Does the ResoluteHow Does the Resolute™™ ZES ZES Perform in Diabetic Patients?Perform in Diabetic Patients?


%% Non-DiabeticsNon-DiabeticsN = 1903N = 1903

Diabetics Diabetics N = 878N = 878

Age (yr)Age (yr) 63.5 ± 10.863.5 ± 10.8 65.2 65.2 ± 10.2± 10.2

MaleMale 74.374.3 66.466.4

Diabetes mellitus Diabetes mellitus 00 100.0100.0

IDDMIDDM 00 28.528.5

HypertensionHypertension 73.1 87.687.6

HyperlipidemiaHyperlipidemia 76.0 86.286.2

Current smokerCurrent smoker 22.1 18.218.2

Family historyFamily history 42.2 37.837.8

Prior MIPrior MI 25.5 24.924.9

Prior PCIPrior PCI 29.5 34.634.6

Prior CABGPrior CABG 7.4 10.510.5

Clinical status:Clinical status:

Stable anginaStable angina 45.5 46.246.2

Unstable anginaUnstable angina 31.3 28.928.9

Myocardial infarctionMyocardial infarction 6.6 5.45.4

Baseline CharacteristicsBaseline Characteristics


Pooled patient level data from RESOLUTE, R-AC, R-Int, R-US and R-Japan trials.


Target Lesion Failure to 2 YearsTarget Lesion Failure to 2 Years


9.6%

7.1%

0Time After Initial Procedure (months)

Diabetics (N = 878)

Cu

mu

lati

ve I

nci

de

nce

of

TL

F

6 12 18 24

20%

15%

10%

0%

6.6%

4.9%

Non-Diabetics (N = 1903)

No. at riskNo. at risk

Non-DiabeticsNon-Diabetics 19031903 18701870 18161816 17631763 17141714

DiabeticsDiabetics 878878 873873 839839 800800 785785

5%

Target lesion failure (TLF) is defined as cardiac death, target vessel myocardial infarction and target lesion revascularization (TLR). Pooled patient level data from RESOLUTE, R-AC, R-Int, R-US and R-Japan trials. The RESOLUTE Pooled analysis was not specifically designed or powered for the analysis shown above.



TLR Cardiac Death

TVMI Stent Thrombosis

TLF

Clinical Outcomes at 24 MonthsClinical Outcomes at 24 Months

Target vessel failure (TVF) is defined as cardiac death, target vessel MI, and clinically driven TVR. Target lesion failure (TLF) is defined as cardiac death, target vessel MI and TLR. TLR is clinically driven. Stent thrombosis is defined as definite or probable (Academic Research Consortium). Pooled patient level data from RESOLUTE, R-AC, R-Int, R-US and R-Japan trials. Resolute Pooled standard risk diabetic analysis was not specifically designed or powered for the endpoints other than TVF

Eve

nts

(%

)

RESOLUTE Pooled analysis, Standard risk diabetics (n=861/878)

TVF


%% Non-DiabeticsNon-DiabeticsN = 1903N = 1903

Non-IDDMNon-IDDMN = 628N = 628

IDDMIDDMN = 250N = 250

Age (yr)Age (yr) 63.5± 10.863.5± 10.8 65.5 65.5 ± 10.3*± 10.3* 64.6 64.6 ± 10.0± 10.0

MaleMale 74.374.3 70.470.4 56.4**56.4**

Diabetes mellitus Diabetes mellitus 00 100.0*100.0* 100.0100.0

IDDMIDDM 00 00 100.0**100.0**

HypertensionHypertension 73.1 86.0* 91.6**

HyperlipidemiaHyperlipidemia 76.0 86.0* 86.8

Current smokerCurrent smoker 22.1 18.6 17.2

Family historyFamily history 42.2 37.6 38.4

Prior MIPrior MI 25.5 25.7 22.9

Prior PCIPrior PCI 29.5 33.9* 36.4

Prior CABGPrior CABG 7.4 11.1* 8.8

Clinical status:Clinical status: *

Stable anginaStable angina 45.5 46.8 44.8

Unstable anginaUnstable angina 31.3 28.5 30.0

Myocardial infarctionMyocardial infarction 6.6 4.3 8.0

Baseline CharacteristicsBaseline Characteristics


*p-value <0.05 Non-IDDM vs. Non-Diabetics ** p-value <0.05 IDDM vs Non-IDDM


Target Lesion Revascularization to 2 YearsTarget Lesion Revascularization to 2 Years



Cu

mu

lati

ve I

nci

de

nce

of

Car

dia

c D

eat

h/T

LR

6 12 18 24

20%

15%

10%

0%



Non-IDDMNon-IDDM 628628 627627 614614 589589 579579

IDDMIDDM 250250 250250 236236 222222 216216

5%


3.4%

2.1%

6.5%

4.3%

5.4%

2.6%

Non-IDDM (N = 628)IDDM (N = 250)

Pooled patient level data from RESOLUTE, R-AC, R-Int, R-US and R-Japan trials. The RESOLUTE Pooled analysis was not specifically designed or powered for the analysis shown above.


Cardiac Death/TVMI to 2 YearsCardiac Death/TVMI to 2 Years


4.1%


Cu

mu

lati

ve I

nci

de

nce

of

Car

dia

c D

eat

h/T

VM

I

6 12 18 24

20%

15%

10%

0%

3.1%




Non-IDDMNon-IDDM 628628 626626 613613 599599 593593

IDDMIDDM 250250 248248 232232 227227 222222

5%


8.6%

3.9%

6.0%

2.6%

Pooled patient level data from RESOLUTE, R-AC, R-Int, R-US and R-Japan trials. The RESOLUTE Pooled analysis was not specifically designed or powered for the analysis shown above.


0.43%

Stent Thrombosis to 2 YearsStent Thrombosis to 2 Years



Cu

mu

lati

ve I

nci

de

nce

of

AR

C D

ef/P

rob

ST

6 12 18 24

10%

8%

6%

0%

4%


2%



Non-IDDMNon-IDDM 628628 627627 617617 604604 598598

IDDMIDDM 250250 250250 240240 234234 229229

0.32%0.80%

0.16%

0.80%

0.16%


Stent thrombosis is definite or probable as defined by the Academic Research Consortium. Pooled patient level data from RESOLUTE, R-AC, R-Int, R-US and R-Japan trials. The RESOLUTE Pooled analysis was not specifically designed or powered for the analysis shown above.


RISICO Diabetic Analysis: RISICO Diabetic Analysis: ResoluteResolute®® ZES Appears to Be Highly Efficacious ZES Appears to Be Highly Efficacious Even in Patients With DiabetesEven in Patients With Diabetes

P = 0.760P = 0.437P = 0.943P = 0.294

Outcomes in Patients With vs Without Diabetes Receiving Resolute ZES

Inci

den

ce, %

ZES = zotarolimus-eluting stent.Lelasi A, et al. Presented at: EuroPCR. 2011.


Summary (I)Summary (I)

• The prevalence of diabetes and The prevalence of diabetes and cardiovascular disease is increasingcardiovascular disease is increasing

• The risk of serious adverse events is The risk of serious adverse events is increased in patients with both diabetes and increased in patients with both diabetes and cardiovascular diseasecardiovascular disease

• Percutaneous coronary intervention Percutaneous coronary intervention procedures in patients with diabetes result in procedures in patients with diabetes result in inferior outcomes inferior outcomes


Summary (II)Summary (II)

• Resolute Integrity™ is the only drug-eluting stent Resolute Integrity™ is the only drug-eluting stent approved to treat patients with diabetes in the United approved to treat patients with diabetes in the United StatesStates

• There is a lack of robust clinical evidence to support There is a lack of robust clinical evidence to support the use of most drug-eluting stents in patients with the use of most drug-eluting stents in patients with diabetesdiabetes

• The ResoluteThe Resolute™™ stent showed consistently low event stent showed consistently low event rates out to two years despite the higher risk nature rates out to two years despite the higher risk nature of this diabetic patient population. of this diabetic patient population.

• The ResoluteThe Resolute™™ stent showed that outcomes in stent showed that outcomes in patients with NIDDM appear to be similar to non-patients with NIDDM appear to be similar to non-diabetic patients.diabetic patients.


IndicationsThe Resolute Integrity Zotarolimus-Eluting Coronary Stent System is indicated for improving coronary luminal diameters in patients, including those with diabetes mellitus, with symptomatic ischemic heart disease due to de novo lesions of length ≤ 27 mm in native coronary arteries with reference vessel diameters of 2.25 mm to 4.20 mm.ContraindicationsThe Resolute Integrity Zotarolimus-Eluting Coronary Stent System is contraindicated for use in: • Patients with a known hypersensitivity or allergies to aspirin, heparin, bivalirudin, clopidogrel, prasugrel, ticagrelor, ticlopidine, drugs such as zotarolimus, tacrolimus, sirolimus, everolimus or similar drugs or any other analogue or derivative • Patients with a known hypersensitivity to the cobalt-based alloy (cobalt, nickel, chromium and molybdenum) • Patients with a known hypersensitivity to the BioLinx® polymer or its individual components Coronary artery stenting is contraindicated for use in: • Patients in whom antiplatelet and/or anticoagulation therapy is contraindicated • Patients who are judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the stent or stent delivery systemWarnings• Please ensure that the inner package has not been opened or damaged as this would indicate the sterile barrier has been breached. • The use of this product carries the same risks associated with coronary artery stent implantation procedures, which include subacute and late vessel thrombosis, vascular complications and/or bleeding events. • This product should not be used in patients who are not likely to comply with the recommended antiplatelet therapy.Precautions• Only physicians who have received adequate training should perform implantation of the stent. • Stent placement should only be performed at hospitals where emergency coronary artery bypass graft surgery can be readily performed. • Subsequent stent restenosis or occlusion may require repeat catheter-based treatments (including balloon dilatation) of the arterial segment containing the stent. The long-term outcome following repeat catheter-based treatments of previously implanted endothelialized stents is not well characterized. • The risks and benefits of the stent implantation should be assessed for patients with a history of severe reaction to contrast agents. • Do not expose or wipe the product with organic solvents such as alcohol. • When drug-eluting stents (DES) are used outside the specified Indications for Use, patient outcomes may differ from the results observed in the RESOLUTE pivotal clinical trials. • Compared to use within the specified Indications for Use, the use of DES in patients and lesions outside of the labeled indications, including more tortuous anatomy, may have an increased risk of adverse events, including stent thrombosis, stent embolization, myocardial infarction (MI), or death • Care should be taken to control the position of the guide catheter tip during stent delivery, deployment, and balloon withdrawal. Before withdrawing the stent delivery system, visually confirm complete balloon deflation by fluoroscopy to avoid guiding catheter movement into the vessel and subsequent arterial damage • Stent thrombosis is a low-frequency event that is frequently associated with MI or death. Data from the RESOLUTE clinical trials have been prospectively evaluated and adjudicated using the definition developed by the Academic Research Consortium (ARC).The safety and effectiveness of the Resolute Integrity stent have not yet been established in the following patient populations: • Patients with target lesions which were treated with prior brachytherapy or the use of brachytherapy to treat in-stent restenosis of a Resolute Integrity stent • Women who are pregnant or lactating • Men intending to father children • Pediatric patients • Patients with coronary artery reference vessel diameters of <2.25 mm or >4.20 mm • Patients with coronary artery lesions longer than 27 mm or

requiring more than one Resolute Integrity stent • Patients with evidence of an acute MI within 72 hours of intended stent implantation • Patients with vessel thrombus at the lesion site • Patients with lesions located in a saphenous vein graft, in the left main coronary artery, ostial lesions, or bifurcation lesions • Patients with diffuse disease or poor flow distal too identified lesions • Patients with tortuous vessels in the region of the target vessel or proximal to the lesion • Patients with in-stent restenosis • Patients with moderate or severe lesion calcification at the target lesion • Patients with occluded target lesions including chronic total occlusions • Patients with three-vessel disease • Patients with a left ventricular ejection fraction of <30% • Patients with a serum creatinine of >2.5mg/dl • Patients with longer than 24 months of follow-upThe safety and effectiveness of the Resolute Integrity stent have not been established in the cerebral, carotid or peripheral vasculature.Potential Adverse EventsOther risks associated with using this device are those associated with percutaneous coronary diagnostic (including angiography and IVUS) and treatment procedures. These risks (in alphabetical order) may include but are not limited to: • Abrupt vessel closure • Access site pain, hematoma or hemorrhage • Allergic reaction (to contrast, antiplatelet therapy, stent material, or drug and polymer coating) • Aneurysm, pseudoaneurysm, or arteriovenous fistula (AVF) • Arrhythmias, including ventricular fibrillation • Balloon rupture • Bleeding • Cardiac tamponade • Coronary artery occlusion, perforation, rupture or dissection • Coronary artery spasm • Death • Embolism (air, tissue, device or thrombus) • Emergency surgery: peripheral vascular or coronary bypass • Failure to deliver the stent • Hemorrhage requiring transfusion • Hypotension/hypertension • Incomplete stent apposition • Infection or fever • MI • Pericarditis • Peripheral ischemia/peripheral nerve injury • Renal failure • Restenosis of the stented artery • Shock/pulmonary edema • Stable or unstable angina • Stent deformation, collapse, or fracture • Stent migration (or embolization) • Stent misplacement • Stroke/transient ischemic attack • Thrombosis (acute, subacute or late) Adverse Events Related to ZotarolimusPatients’ exposure to zotarolimus is directly related to the total amount of stent length implanted. The actual side effects/complications that may be associated with the use of zotarolimus are not fully known. The adverse events that have been associated with the intravenous injection of zotarolimus in humans include but are not limited to: • Anemia • Diarrhea • Dry skin • Headache • Hematuria • Infection • Injection site reaction • Pain (abdominal, arthralgia, injection site) • RashPlease reference appropriate product Instructions for Use for more information regarding indications, warnings, precautions and potential adverse events.CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician.

All brand names, product names or trademarks belong to their respective holders.

ResoluteResolute™™ DES Safety Information DES Safety Information


IndicationsThe Endeavor® Sprint Zotarolimus-Eluting Coronary Stent Delivery System is indicated for improving coronary luminal diameter in patients with ischemic heart disease due to de novo lesions of length ≤27 mm in native coronary arteries with reference vessel diameters of ≥2.5 mm to ≤3.5 mm.ContraindicationsThe Endeavor Zotarolimus-Eluting Coronary Stent System is contraindicated for use in:• Patients with a known hypersensitivity to zotarolimus or structurally related compounds • Patients with a known hypersensitivity to the cobalt-based alloy (cobalt, nickel, chromium, and molybdenum) • Patients with a known hypersensitivity to Phosphorylcholine polymer or its individual components.Coronary artery stenting is contraindicated for use in:• Patients with a known hypersensitivity or allergies to aspirin, heparin, clopidogrel or ticlopidine • Patients who cannot receive recommended antiplatelet and/or anticoagulation therapy • Patients who are judged to have a lesion that prevents complete inflation of an angioplasty balloon or proper placement of the stent or stent delivery system.Warnings• Please ensure that the inner package has not been opened or damaged, as this indicates the sterile barrier has been breached • The use of this product carries the risks associated with coronary artery stenting, including subacute thrombosis, vascular complications, and/ or bleeding events • This product should not be used in patients who are not likely to comply with the recommended antiplatelet therapy.Precautions• Only physicians who have received adequate training should perform implantation of the stent • Stent placement should only be performed at hospitals where emergency coronary artery bypass graft surgery can be readily performed • Subsequent stent blockage may require repeat dilatation of the arterial segment containing the stent. The long-term outcome following repeat dilatation of endothelialized stents is not well characterized • Risks and benefits of the stent should be assessed for patients with history of severe reaction to contrast agents • Do not expose or wipe the product with organic solvents such as alcohol or detergents • Stent thrombosis is a low-frequency event that current drug-eluting stent (DES) clinical trials are not adequately powered to fully characterize. Stent thrombosis is frequently associated with myocardial infarction (MI) or death. Data from the ENDEAVOR randomized clinical trials have been prospectively evaluated and adjudicated using both the protocol definition of stent thrombosis and the definition developed by the Academic Research Consortium (ARC), and demonstrate specific patterns of stent thrombosis that vary depending on the definition used. In the ENDEAVOR clinical trials analyzed to date, the differences in the incidence of stent thrombosis observed with the Endeavor stent compared to bare metal stents have not been associated with an increased risk of cardiac death, MI, or allcause mortality. Additional data from longer-term follow-up in the ENDEAVOR randomized clinical trials and analyses of DES-related stent thrombosis are expected and should be considered in making treatment decisions as data become available • When DES are used outside the specified Indications for Use, patient outcomes may differ from the results observed in the pivotal clinical trials • Compared to use within the specified Indications for Use, the use of DES in patients and lesions outside of the labeled indications, including more tortuous anatomy, may have an increased risk of adverse events, including stent thrombosis, stent embolization, MI, or death.

The safety and effectiveness of the Endeavor stent have not yet been established in the following patient populations:• Women who are pregnant or lactating • Men intending to father children • Pediatric patients • Patients with vessel thrombus at the lesion site • Patients with coronary artery reference vessel diameters <2.5 mm or >3.5 mm • Patients with coronary artery lesions longerthan 27 mm or requiring more than one Endeavor stent • Patients with lesions located in saphenous vein grafts, in the unprotected left main coronary artery, ostial lesions, or lesions located at a bifurcation • Patients with diffuse disease or poor flow distal to the identifiedlesions • Patients with multivessel disease • Patients with tortuous vessels in the region of the obstruction or proximal to the lesion • Patients with a recent acute myocardial infarction where there is evidence of thrombus or poor flow • Patients for longer than 48 months of follow-up • Patients with in-stent restenosis • Patients with moderate or severe calcification in the lesion or a chronic total occlusion • Patients with prior brachytherapy of the target lesion or the use of brachytherapy to treat in-stent restenosis in an Endeavor stent.The safety and effectiveness of the Endeavor stent have not been established in the cerebral, carotid, or peripheral vasculature.Potential Adverse EventsOther risks associated with using this device are those associated with percutaneous coronary diagnostic (including angiography and IVUS) and treatment procedures. These risks may include, but are not limited to • Abrupt vessel closure • Access site pain, hematoma or hemorrhage • Allergic reaction (to contrast, antiplatelet therapy, stent material, or drug and polymer coating) • Aneurysm, pseudoaneurysm, or arteriovenous fistula (AVF) • Arrhythmias • Balloon rupture • Cardiac tamponade • Coronary artery occlusion, perforation, rupture, or dissection • Coronary artery spasm • Death • Embolism (air, tissue, device, or thrombus) • Emergency surgery: peripheral vascular or coronary bypass • Failure to deliver the stent • Hemorrhage requiring transfusion • Hypotension/hypertension • Incomplete stent apposition • Infection or fever • Late or very late thrombosis • Myocardial infarction (MI) • Myocardial ischemia • Peripheral ischemia/peripheral nerve injury • Renal failure • Restenosis of the stented artery • Rupture of native or bypass graft • Shock/pulmonary edema • Stent deformation, collapse, or fracture • Stent migration • Stent misplacement • Stroke/transient ischemic attack • Thrombosis (acute and subacute) • Unstable angina • Ventricular fibrillation.Adverse Events Related to ZotarolimusPatients’ exposure to zotarolimus is directly related to the total amount of stent length implanted. The actual side effects/complications that may be associated with the use of zotarolimus are not fully known. The adverse events that have been associated with the intravenous injection of zotarolimus in humans include • Anemia • Application site reaction • Diarrhea • Dry skin • Headache • Hematuria • Infection • Injection site reaction • Pain (abdominal, arthralgia, injection site) • Rash.Please reference appropriate product Instructions for Use for more information regarding indications, warnings, precautions and potential adverse events.CAUTION: Federal (USA) law restricts this device to sale by or on the order of a physician.

All brand names, product names or trademarks belong to their respective holders.

Endeavor DES Safety InformationEndeavor DES Safety Information

trademarks may be registered and are the property of their respective owners. © 2012 medtronic,...

Documents

resolute des population

resolute us

resolute japan

drug release

prespecified analysis

respective owners

cohort diabetic population

standard risk matched