summary of safety and effectiveness data …...2012/02/22 · there are several other treatment...

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED)

I GENERAL INFORMATION

Device Generic Name

Device Trade Name

Applicants Name and Address

Date of Panel Recommendation

Premarket Approval Application (PMA) Number

Date of FDA Notice of Approval

Expedited

Drug-Eluting Coronary Stent System (NIQ)

IONTMPaclitaxel-Eluting Coronary StentSystem (Monorail and Over-the-Wire)

Boston Scientific Corporation One Boston Scientific Place Natick MA 01760-1537

None

P100023S015

February 22 2012

Not applicable

The original PMA (P100023) was approved on April 22 2011 and is indicated for improvingluminal diameter for the treatment of de novo lesions in native coronary arteries gt225 to lt400 mm in diameter in lesions lt 34 mm in length The SSED to support the indication is available on the CDRH website and is incorporated by reference here httpwwwaccessdatafdagovcdrh-docspdfl oP 100023bpdf

This supplement approval revises the indications statement to include patients undergoingprimary angioplasty to treat acute ST-segment elevation myocardial infarction true posteriormyocardial infarction or presumed new left bundle branch block with symptoms of acute myocardial infarction lasting gt 20 minutes and lt 12 hours in duration

II INDICATIONS FOR USE

The ION Stent System is indicated for improving luminal diameter

for the treatment of de novo lesions in native coronary arteries 225 mm to 400 mm in diameter in lesions lt 34 mm in length or

undergoing primary angioplasty to treat acute ST-segment elevation in patients myocardial infarction true posterior myocardial infarction or presumed new left

bundle branch block with symptoms of acute myocardial infarction lasting gt 20 minutes and lt 12 hours in duration

III CONTRAINDICATIONS

Use of the ION Stent System is contraindicated in patients with

Known hypersensitivity to 316L stainless steel or platinum

Known hypersensitivity to paclitaxel or structurally-related compounds

Known hypersensitivity to the polymer or its individual components

Coronary Artery Stenting is contraindicated for use in a Patients who cannot receive recommended antiplatelet aridor anticoagulant therapy

0 Patients judged to have a lesion that prevents complete inflation of an angioplasty

balloon or proper placement of the stent or delivery device

IV WARNING AND PRECAUTIONS

The warnings and precautions can be found in the ION Paclitaxel-Eluting Coronary Stent

System Directions for Use (DFU)

V DEVICE DESCRIPTION

drug The ION Paclitaxel-Eluting Coronary Stent System is a device combination product

a device (Element Coronary Stent System) and a comprised of two regulated components

The componentsdrug product (a formulation of paclitaxel contained in a polymer coating) of the ION Paclitaxel-Eluting Coronary Stent System are identical to the and characteristics

Please refer to the original device description for additionalproduct approved in P100023 details The characteristics of the ION Stent System are described in Table 1

page PMA P 100023SO15 FDA Summary of Safety and Effectiveness Data 2

Table I ION Stent S stem Product Descri tion

Available Stent Lengths (mm)

8 12 162024 283238

Available Stent Diameters (mm)

225 250 275 300 350 400

Stent Material Stent Strut

Thickness

Platinum Chromium Alloy (PtCr) 0 00032 in (0081 mm) for diameters 225 min to 35 mm 00034 in (0086 mm) for diameter 40 mm

Drug Product A conformal coating of a polymer carrier loaded with I igmm 2 paclitaxel applied to the stent with a maximum nominal drug content of 247 Vg on the largest stent (400 x

38 mm)

Delivery System

Effective Length 144 cm 143 cm

Delivery System Y-Adapter Ports

Y-Connector (Side arm for access to Single access port to inflation lumen balloon inflationdeflation lumen Guidewire exit port is located Straight arm is continuous with shaft approximately 26 cm from tip Designed for inner lumen) Designed for guidewire S guidewire5 0014 in (036 mm) 0014 in (036 mm)

Stent Delivery A balloon with two radiopaque balloon markers nominally placed 0385 mm (0015 in) beyond the stent at each end

Nominal Inflation Pressure Diameters 225 mm 250 mm 275 mm 300 mm 350 mm 400 mm II atm (1115

Balloon Inflation kPa) Pressure

Rated Burst Inflation PressureDiameters 225 mm 18 atm (1824 kPa)Diameters 250 mm 275 mm 300 mm 350 mm 400 mm 16 atm (1621 kPa)

Catheter Shaft Outer Diameter

23 F (080 mm) proximal and 27 F (095 mm) distal

34F (120 mm) proximal for 225 to 400 mm sizes 24F (085 mm) distal for 225 to 275 mm sizes 27F (095 mm) distal for 300 to 400 mm sizes

Guide Catheter Minimum Inner Diameter

gt 0056 in (142 mm) for 225 to 350 mm -sizes 0066 in (168 mm)

Requirement gt 0058 in (147 mm) for 400 mm sizes

225 and 250 mm sizes are available in 8 12 16 20 24 28 32 mm lengths

PMA P100023SO 15 FDA Summary of Safety and Effectiveness Data page 3

VI ALTERNATIVE PRACTICES OR PROCEDURES

There are several other treatment alternatives for coronary artery disease exercise diet drug therapy percutaneous coronary interventions (such as angioplasty and placement of bare metal stents coated stents and other drug eluting stents) and coronary artery bypass surgery (CABG) A patient should fully discuss these alternatives with hisher physician to select the method that best meets expectations and lifestyle

VII MARKETING HISTORY

ION Paclitaxel-Eluting Coronary Stent System is commercially available in the following countries Note that ION is marketed as TAXUS Element outside the US but the product is identical to ION The device has not been withdrawn from marketing for any reason related to its safety or effectiveness

Albania Dutch Antilles Lebanon Saudi Arabia Algeria Ecuador Libya Scotland AntiguaBarbuda Egypt Liechtenstein SerbiaMontenegro Argentina El Salvador Lithuania Singapore Armenia Estonia Luxembourg Slovakia Aruba Finland Macau Slovenia Australia France Macedonia South Africa Austria Georgia Malaysia Spain Bahamas Germany Malta Sri Lanka Bahrain Great Britain Martinique Sudan Bangladesh Greece Mauritania Suriname Barbados Guatemala Mauritius Sweden Belarus Guyana Mexico Switzerland Belgium Haiti Moldavia Syria Belize Honduras Morocco Taiwan Bermuda Hong Kong Myanmar Thailand Bolivia Hungary Nepal TrinidadTobago Bosnia Iceland Netherlands Tunisia Brazil India New Zealand Turkey Brunei Indonesia Nicaragua United Arab Emirates Bulgaria Iran Norway Ukraine Canada Iraq Oman Uruguay Chile Ireland Pakistan Venezuela China Israel Panama Vietnam Colombia Italy Paraguay West Bank Gaza Strip Costa Rica Jamaica Peru Yemen Croatia Japan Philippines Cyprus Jordan Romania Dominican Rep Latvia Russia

PMA P100023S015 FDA Summary of Safety and Effectiveness Data page 4

VIII POTENTIAL ADVERSE EFFECTS OF THE DEVICE ON HEALTH

Below is a list of the potential adverse effects (eg complications) in alphabetical order which may be associated with the use of a coronary stent in coronary arteries

Abrupt stent closure Acute myocardial infarction Allergic reaction to anticoagulants or antithrombotic therapy or contrast medium or stent

materials Angina Arrhythmias including ventricular fibrillation (VF) and ventricular tachycardia (VT) Arteriovenous fistula Cardiac tamponade Cardiogenic shock pulmonary edema Death Dissection Emboli distal (air tissue or thrombotic material or material from device(s) used in the

procedure) Heart failure Hematoma Hemorrhage requiring transfusion Hypotensionhypertension Infection local andor systemic Ischemia myocardial Pain at the access site Perforation or rupture of coronary artery Pericardial effusion Pseudoaneurysm femoral Renal failure Respiratory failure Restenosis of stented segment Shock Stent embolization Stent migration Stent thrombosisocclusion Strokecerebrovascular accidentTIA Total occlusion of coronary artery Vessel spasm Vessel trauma requiring surgical repair or reintervention

Potential adverse events not captured above that may be unique to the paclitaxel drug coating Allergicimmunologic reaction to drug (paclitaxel or structurally-related compounds) or

the polymer stent coating (or its individual components)AlopeciaAnemia

PMA P100023SO15 FDA Summary of Safety and Effectiveness Data page 5

Blood product transfusion Gastrointestinal symptoms Hematologic dyscrasia (including leukopenia neutropenia thrombocytopenia) Hepatic enzyme changes Histologic changes in vessel wall including inflammation cellular damage or necrosis Myalgia arthralgia Peripheral neuropathy

For the specific adverse events that occurred in the HORIZONS AMI clinical study please see Section X below

IX SUMMARY OF PRECLINICAL STUDIES

A series of non-clinical laboratory studies were performed to support the original approval shythose related to the stent and the stent delivery system [ie the stent on either the Monorail (MR) or Over-The-Wire (OTW) stentdelivery system (SDS)] the polymer substance [ie poly(styrene-b-isobutylene-b-styrene) (SIBS)] the drug substance (ie paclitaxel) and the finished combination product (ie IONTM Paclitaxel-Eluting Coronary Stent) No new nonclinical studies were needed to support the approval of this supplement


X SUMMARY OF CLINICAL STUDIES

A program of clinical studies (PERSEUS Workhorse and PERSEUS Small Vessel) was performed to support the original approval Please refer to previous SSED for details The HORIZONS AMI trial was performed to establish a reasonable assurance of safety and effectiveness for TAXUS Express2 Paclitaxel-Eluting Coronary Stent System for the proposed expanded indication under IDE G040188 Data from this clinical study were the basis for the PMA approval decision The ION stent uses the same drug-polymer coating formulation as the TAXUS ExpreSS2 stent In addition nonclinical studies of design attributes and the PERSEUS clinical studies in stable patients with coronary artery disease have established that the performance of the ION is similar Given these supportive data outcomes in patients with AMI would also be expected to be similar between these two stents and therefore the safety and effectiveness data from the HORIZONS AMI trial were considered applicable for the ION Paclitaxel-Eluting Coronary Stent System aswell A summary of the clinical study is presented below

A HORIZONS AMI Clinical Trial

Objectives The trial had two primary objectives and was designed and powered to address both the primary and sub-study objectives

Primary objective for the pharmacology randomization To evaluate the use of bivalirudin in patients with ST segment elevation acute myocardial infarction (STEMI) undergoing a primary angioplasty strategy compared to unfractionated heparin plus routine use of GP IlbIlla inhibitors

Primary objective for the stent randoinization To establish the safety and effectiveness of the paclitaxel-eluting TAXUS Express stent in STEMI patients by showing that compared to an otherwise identical Express BMS the TAXUS Express results in (1) reduced rates of ischemia-driven target lesion revascularization at 1 year (2) a similar rate of the composite of death reinfarction stroke or stent thrombosis at 1 year and (3) a lower rate of analysis segment binary angiographic restenosis at 13 months

Design

The HORIZONS AMI trial was a prospective dual-arm single-blind randomized multi-center trial that enrolled STEMI patients defined by clinical symptoms consistent with acute MI lasting greater than 20 minutes but less than 12 hours and specific ECG criteria consisting of ST-segment elevation ofgt Imm in gt 2 contiguous leads presumed new LBBB or true posterior MI with ST depression ofgt 1mm in gt 2 contiguous anterior leads A total of 3602 patients were randomized (primary randomization) in a 11 fashion in the emergency room to anticoagulation with unfractionated heparin plus routine GP IlbIla inhibition or bivalirudin and bail-out GP IlbIla inhibition


Emergent coronary angiography with left ventriculography was performed after the primary randomization followed by triage to either percutaneous coronary intervention (PCI) coronary artery bypass graft (CABG) surgery or medical management at physician discretion

After coronary angiography a total of 3006 patients were triaged to PCI and randomized (secondary randomization) in a 31 fashion to either a TAXUS Express stent or an Express stent In order to be eligible for the second randomization patients had to have at least one acute infarct-related artery with an expectation that study stents could be delivered to all culprit lesions Exclusion criteria included true bifurcation lesions definitely requiring stenting of the side branch vessel lesions requiring greater than 100 mm of stent length unprotected left main culprit lesions and stent thrombosis lesions The secondary randomization was stratified by the following four factors the result from the primary randomization (to ensure equal distribution of the two arms from the primary randomization in the secondary randomization) the presence or absence of medically treated diabetes whether any of the lesions were greater than 26 mm in length such that overlapping stents would be used and whether the clinical study site was within or outside of the US

Table 2 HORIZONS AMI CLINICAL TRIAL OVERVIEW

HORIZONS AMI (Indication Expansion)

Study Type Prospective multicenter randomized single-blind

Number of Patients (ITT) Total 3006TAXUS 2257Control 749

Dose Release Formulation Slow Release (SR) (1 pg mm2)

Lesion Criteria Vessel Diameter (by visual estimate) gt 25 mm to lt 40 m

Lesion Criteria Lesion Length (by visual estimate) lt 100 mm

Product Used TAXUS Express Paclitaxel-Eluting Coronary StentSystem

Antiplatelet Therapy Aspirin indefinitely and clopidogrel or ticlopidine for 6 months (1 year or longer recommended)

Follow-Up

30 days clinical 6 months clinical 12 month clinical 13 month angiographicIVUS 2 3 years clinical

Abbreviations ITT=intent-to-treat IVUS=intravascular ultrasound

1 Clinical Inclusion and Exclusion Criteria

Primary Randomization - Inclusion Criteria


1 The patient must be at least 18 years of age (there is no upper age limit) 2 Must have clinical symptoms consistent with AMI (eg angina or anginal equivalent)

lasting gt20 minutes but lt12 hours in duration If the symptom duration at the time of evaluation is lt1 hour to rule out unstable angina the symptoms must be unresponsive to nitroglycerin (ie ongoing) prior to signing the informed consent Patients with symptom onset within 12 hours in whom the symptoms lasted gt1 hour but subsequently resolved may still be enrolled if the ECG at the time ofthe evaluation shows definite ongoing ST segment elevation

3 ECG criteria ST-segment elevation ofgt 1 mm in gt 2 contiguous leads or (presumably new) left bundle branch block or true posterior MI with ST depression of gt 1 mm in gt 2 contiguous anterior leads

4 The patient or guardian agrees to the study protocol and the schedule of clinical and angiographic follow-up and provides informed written consent as approved by the appropriate Institutional Review BoardEthical Committee of the respective clinical site

Primary Randomization - Exclusion Criteria

1 The patient has a known hypersensitivity or contraindication to any of the following medications o Heparin pork or pork products Both abciximab and eptifibatide Aspirin o Both Clopidogrel and Ticlopidine Bivalirudin Paclitaxel or Taxol The polymer components of the TAXUS Express DES stent (SIBS) Stainless steel andor Contrast media (patients with documented sensitivity to contrast which can be

effectively pre-medicated with steroids and diphenhydramine (eg rash) may be enrolled Patients with true anaphylaxis to prior contrast media however should not be enrolled)

2 Prior administration of thrombolytic therapy bivalirudin GP IlbIla inhibitors low molecular weight heparin or fondaparinux for this admission Patients receiving prior unfractionated heparin may be enrolled and treated per randomization

3 Current use of coumadin 4 Systemic (intravenous) Paclitaxel or Taxol use within 12 months 5 Female of childbearing potential unless a recent pregnancy test is negative who possibly

plans to become pregnant any time after enrollment into this study 6 History of bleeding diathesis or known coagulopathy (including heparin-induced

thrombocytopenia) or will refuse blood transfusions 7 History of intra-cerebral mass aneurysm arteriovenous malformation or hemorrhagic

stroke 8 Stroke or transient ischemic attack within the past 6 months or any permanent residual

neurologic defect 9 Gastrointestinal or genitourinary bleeding within the last 2 months or major surgery

within six weeks


10 Recent history or known current platelet count lt100000 cellsmm3 or Hgb lt10 gdL (note baseline labs did not have to be available prior to enrollment)

11 Extensive peripheral vascular disease such that emergent angiography and intervention in the opinion of the investigator is likely to be difficult or complicated

12 An elective surgical procedure is planned that would necessitate interruption ofthienopyridines during the first six months post enrollment

13 Non-cardiac co-morbid conditions are present with life expectancy lt1 year or that may result in protocol non-compliance

14 Patients who are actively participating in another drug or device investigational study which have not completed the primary endpoint follow-up period

15 Previous enrollment in this trial 16 Patients who underwent coronary stent implantation within the past 30 days

Secondary Randomization - Angiographic Inclusion Criteria

1 At least one acute infarct artery target vessel is present in which a ALL hemodynamically significant lesions can be stented with study stents and b ALL such lesions have a visually estimated reference diameter gt225 mm and lt

40 mm 2 Expected ability to deliver the stent(s) to all culprit lesions (absence of excessive

proximal tortuosity or severe calcification)3 Expected ability to fully expand the stent(s) at all culprit lesions (absence of marked

calcification)

Secondary Randomization - Angiographic Exclusion Criteria

1 One or more hemodynamically significant lesion(s) is present in the infarct vessel (or side branches) which can only undergo balloon angioplasty or cannot be stented with a study stent (ie do not meet the angiographic inclusion criteria for a study stent)

Note The only exception to this exclusion criterionis bifurcationlesions with main branchand ostialside branch involvement which may be enrolledas long as the main branchis eligible to be treatedwith a study stent The ostialside branch lesion should then be treatedwith balloonangioplastywith bail-outstentingperformedonlyfor asubshyoptimalresult in the side branch (diameterstenosis gt50 or dissection NHLBI type C refractoryto prolonged(gt2 minute) balloon inflations) Bifurcationlesions are otherwise excluded if the plannedstrategydefinitely requires2 stents (eg plannedT-stenting Vshystenting culotte stentingor crush)

2 The presence of a bifurcation lesion in the infarct vessel which will definitely require the implantation of two stents for treatment

Note A true bifurcationlesion qualifiesfor randomizationif the operatorbelieves heshe will be likely able to successfully approachthe lesion with provisionalstenting (ie the side branch ostiallesion is dilatedfirstandstented onlyfor a sub-optimalresult as defined above afterprolonged(gt2 minute) balloon inflations)


3 Anticipated need for greater than 100mm of study stent length 4 The infarct related artery is an unprotected left main segment 5 Patients with significant multi-vessel disease or anatomical features otherwise

unfavorable for angioplasty such that the patient will have a high likelihood of requiring bypass surgery prior to 30 days

6 The culprit vessel or lesion cannot be identified 7 Patient presenting with possibleprobable stent thrombosis 8 Any patient in whom angiography demonstrates the infarct lesion to be at the site of a

previously implanted stent (bare metal or drug-eluting)

2 Follow-up Schedule

Clinical follow-up was performed at 30 days (plusmn 1 week) 6 months (plusmn 2 weeks) 1 year (plusmn 2 weeks) 2 years (plusmnI month) and 3 years (plusmn 1 month) Angiographic follow-up was performed at 13 months (-2 weeks + 52 weeks) for a subset of patients (approximately the first 1500 randomized patients) Certain sites also participated in the HORIZONS IVUS substudy where intravascular ultrasound was performed at baseline (post-procedure) and at 13 month follow-up (approximately the first 400 patients)

3 Clinical Endpoints

Primary Efficacy Endpoint Ischemic target lesion revascularization Primary Safety Endpoint The composite rate of death reinfarction stent thrombosis or

stroke (MACE) Major Secondary Endpoint Analysis segment binary restenosis in the 13 month

angiographic subset

All primary and major secondary endpoints were analyzed both on an intent-to-treat (ITT) basis (all patients analyzed as part of their assigned treatment group) and on a perprotocol basis (patients analyzed as part of their assigned treatment group only if they actually received their assigned treatment) The principal analyses were by intention-to-treat

The primary and major secondary endpoints were analyzed using risk differences and compared to the pre-specified non-inferiority margin Kaplan-Meier curves and survival analyses were also constructed Secondary efficacy and safety data were analyzed using descriptive statistics

For principle statistical analyses all endpoints were analyzed on a per patient basis

B Accountability of PMA Cohort

Refer to Table 3 for primary endpoint patient disposition

Table 3 Patient Disposition TAXUS DES EXPRESS2 BMS Combined

N-2257 N-749 N-3006 Patients Enrolled (ITT Population) 1000 (22572257) 1000 (749749) 1000 (30063006)


Table 3 Patient Disposition TAXUS DES EXPRESS2 BMS Coinbined

~ ~ N=2257~ N=749 N=3006Completed 1year follow-up 969 (21862257) 955 (715749) 965 (29013006)Reason not completed Lost to Follow-up 30 (682257) 40 (30749) 33 (983006)PatientPhysician withdrawal 09 (202257) 11 (8749) 09 (283006)Death 34 (762257) 35 (26749) 34 (1023006)

Patients qualified for PP analysis 951 (21462257) 960 (719749) 953 (28653006)(29823006)Stented Patients 992 (22382257) 993 (744749) 992

Includes patients with 30 day 6 month or 1year follow-up or any follow-up visit post the follow-up window or any MACE event-

C Study Population Demographics and Baseline Parameters

The baseline demographics and medical history are reported in Table 4

Table 4 HORIZONS AMI Patient Demographics and Medical History (ITT Population)TAXUS Express Bare Metal Express

(N=2257) (N=749)Age (median (IQR) yrs) 599 (524 694) 593 (518 692) Male 770 (17382257) 760 (569749)Diabetes mellitus 161 (3642256) 152 (114749)- Insulin requiring 43 (982256) 41 (31749)Hypertension 512 (1152256) 519 (389749)Hyperlipidemia 422 (9532256) 411 (308749)Current smoker 463 (10412246) 519 (388748)Prior myocardial infarction 91 (2062256) 109 (82749)Prior percutaneous coronary intervention 95 (2142255) 77 (58749)Prior coronary artery bypass graft 22 (502256) 19 (14749)Anemia 110 (2352130) 76 (54715)Killip class 2-4 88 (1992254) 80 (60748)Renal insufficiency 156 (3282102) 154 (107696)

40 143 (2791948) 140 (91652)LVEF IQR = interquartile range Defined using the World Health Organization (WHO) criteria as a hernatocrit value at initial presentation of lt39 for men and lt36 for women 2 Baseline calculated creatinine clearance using the Cockcroft-Gault equation lt60 mLmin

Left ventricular ejection fraction visual assessment from the baseline contrast left ventriculogram

D Safety and Effectiveness Results

The primary and secondary endpoints of the trial were met and are reported in Table 5 and Table 6 The clinical results of the trial are reported in Table 7 In Figure 1 the rates of ischemic TLR are illustrated for all patients and those patients who were not in the protocol required angiographic subset Figures 2-6 provide results of major clinical outcomes to 3 years Angiographic and IVUS results are reported in Table 8


Table 5 HORIZONS AMI Primary Endpoints

TAXUS Express Bare Metal Difference Hazard Ratio P-value Ischemic TLR (N=2257) Express (95 CI) (95 CI)

(N=749)

1 Year 45 (98) 75 (54) -30 (-51 -09) 059 (043 083) 00018

Safety MACE2 TAXUS Express Bare Metal Difference (95CI) Hazard Ratio P-value3

(N=2257) Express (95 CI)

(N=749) 1Year 81 (181) 80 (59) 01 (-21 24) 102 (076 136) 00075

lP-value for the test of superiority2 Safety MACE includes death reinfarction stroke or stent thrombosis

P-value for the test of non-inferiority

Table 6 HORIZONS AMI Secondary Endpoint Binary TAXUS Bare Metal Difference Hazard Ratio P-valueshyRestenosis Express Express (95 CI) (95YCI) (Per Lesion) (N=2257) (N=749)

13 Month 100 (1081081) 229 (76322) -129 (-180 -78) 044 (033 057) lt00001 P-value superiority

Adverse effects that occurred in the PMA clinical study

Observed adverse event experience comes from the HORIZONS AMI trial Major clinical events for this study are shown in Table 6

Table 7 HORIZONS AMI Kaplan-Meier Estimates of Clinical Endpoints at 30 Day 1 2 and 3 Years (ITT Population)

TAXUS Express cBareMetal Expres (N=2257) (N=749)

30 Day Clinical Endpoints Net Adverse Clinical Events 103 (232) 90 (67) MACE 12 48 (109) 45(34) MACE 2 (Safety MACE) 45 (102) 43 (32) Death 21(47) 19(14)

- Cardiac 20(44) 17(13) - Noncardiac 01 (3) 01 (1) Reinfarction 17 (37) 22 (16) - Q wave 12(28) 16(12) - Non Q wave 04(10) 05(4) Death or reinfarction 36 (80) 35 (26) Ischemic TVR 23 (51) 26 (19) Ischemic TLR 21(46) 26(19) Stroke 05(11) 05(4)

Major bleeding (non-CABG) 71 (159) 56 (42)

Target Lesion stent thrombosis 23 (50) 27 (20) 1 Year Clinical Endpoints Net Adverse Clinical Events 158 (355) 163(121)MACE 1 106 (237) 124 (92)


Table 7 HORIZONS AMI Kaplan-Meier Estimates of Clinical Endpoints at 30 Day 1 2 and 3 Years (ITT_ Population)

TAXSxpes BreMetal Express

_____________________ (N=2257)A (N=749)

MACE 2 (Safety MACE)3 81 (181) 80 (59) Death 35(78) 35 (26) - Cardiac 24(54) 27 (20)

- Noncardiac 11(24) 08 (6) Reinfarction 37(81) 45 (33)

- Q wave 20(45) 19(14) - Non Q wave 18(39) 26(19) Death or reinfarction 68(152) 70 (52) Ischemic TVR 59 (129) 88 (64) Ischemic TLR 46 (101) 74 (54) Stroke 10(23) 07(5) Major bleeding (non-CABG) 77 (172) 66 (49) Target Lesion stent thrombosis 31 (69) 34 (25)

2 Year Clinical Endpoints

Net Adverse Clinical Events 215 (480) 260 (191) MACE 1 168(373) 222(162) MACE 2 (Safety MACE) 110 (245) 112 (82) Death 43(96) 53(39) - Cardiac 27(60) 33 (24) - Noncardiac 17 (36) 21 (15) Reinfarction 57 (123) 60 (43)

- Q wave 31(67) 28(20) - Non Q wave 30 (64) 32 (23) Death or reinfarction 94(210) 98 (72) Ischemic TVR 109(236) 167(119) Ischemic TLR 83 (180) 142 (101) Stroke 14(30) 11(8) Major bleeding (non-CABG) 80 (178) 70 (52) Target Lesion stent thrombosis 42 (91) 41 (30)

3 Year Clinical Endpoints Net Adverse Clinical Events1 245 (544) 280 (205) MACE 12 200 (441) 240 (175) MACE 2 (Safety MACE) 136 (300) 129 (94)

Death 56(123) 66(48) - Cardiac 32(71) 38(28) - Noncardiac 24 (52) 29 (20) Reinfarction 70 (150) 66 (47) - Q wave 35(75) 28(20) - Non Q wave 40 (84) 38 (27) Death or reinfarction 118 (260) 115 (84) Ischemic TVR 124 (265) 176 (125) Ischemic TLR 94 (202) 151 (107) Stroke 16(35) 14 (10) Major bleeding (non-CABG) 84 (188) 73 (54)

Target Lesion stent thrombosis 48 (103) 43 (31) Net Adverse Clinical Events includes MACE I and non-CABG related major bleeding 2MACEl includes death reinfarction stroke or ischemic target vessel revascularization

MACE2 includes death reinfarction stent thrombosis or stroke


All All PaientsNon-Anglo ae-no SubsetPatients um

18 18

- TAXUS DES (n=2257) _ TAXUS DES (n=1346) EXPRESS BMS (n=749) -- EXPRESS BMS (n=456)

15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6

-b i Time in Months N Time in Months 881 TAXUS060 2257 2104 2042 1942 1902 1846 1277 TAXUSDES 1346 1208 1164 1112 1090 1051

EXPRESS 8MS 676 600 598 587 507 372 EXPRESS BMS456 394 381 301 353 338 215 749

1 For Figure HORIZONS AMI Cumulative Rates of Ischemic Target Lesion Revascularization to 3 Years All Patients and Patients Not in the Protocol Required Angiographic Subset

18shyTAXUS DES (n=2257)EXPRESS BMS (n=749)

15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36

Time in Months Number at Risk TAXUS DES 2257 2094 2037 1971 1928 1875 1289 EXPRESS BMS 749 684 669 648 634 615 412

or 2 Stent Figure HORIZONS AMI Cumulative Rates of Safety MACE (Death Reinfarction Thrombosis Stroke) to 3 Years


8shyTAXUS DES (n=2257)

7 -- EXPRESS BMS (n=749)

6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36


Figure 3 HORIZONS AMI Cumulative Rates of All Death to 3 Years


5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36


Figure 4 HORIZONS AMI Cumulative Rates of Cardiac Death to 3 Years



7- EXPRESS BMS (n=749)

6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36

Time in MonthsNumber at Risk TAXUS DES 2257 2118 2066 2002 1961 1910 1316 EXPRESS BMS 749 690 676 654 643 624 419

Figure 5HORIZONS AMI Cumulative Rates of Reinfarction to 3 Years

6-- TAXUS DES (n=2238)

EXPRESS BMS (n=744) -

C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36

Numbert~iskTime in MonthsTAXUS DES 2238 2108 2066 2013 1980 1932 1341EXPRESS BMS 744 695 683 664 654 637 425

Figure 6 HORIZONS AMI Cumulative Rates of ARC Definite and Probable Stent Thrombosis to 3 Years


Table 8 HORIZONS AMI 13 Month Angiographic and IVUS Results)QCA TAXUS Express Bare Metal Express

(N=910 Patients 1081 Lesions) (N=293 Patients 332 lesions)

Follow-up MLD in-stent (mm) 236 plusmn 075 (1062) 198 plusmn 082 (328) Follow-up MLD in-segment (mm) 209 plusmn 068 (1062) 184 plusmn 076 (328) Follow-up DS in-stent 187 plusmn 228 (1062) 326 plusmn 249 (328)

Follow-up DS in-segment 288 plusmn 196 (1062) 374 plusmn 220 (328) Late Loss in-stent (mm) 041 plusmn 064 (1062) 082 plusmn 070 (328) Late Loss in-segment (mm) 030 plusmn 056 (1062) 059 plusmn 064 (328) Binary restenosis in-stent 82 (871062) 210 (69328) Binary restenosis in-segment 96 (1021062) 232 (76328) IVUS TAXUS Express Bare Metal Express

(N=196 pts 219 lesions) (N=62 pts 67 lesions)

Neointimal Volume (mm) 194 plusmn 216 (191) 374 plusmn 300 (65) Percent net volume obstruction () 79 + 74 (191) 198 plusmn 158 (65) Incomplete Apposition (late) 583 (95163) 333 (1236) Incomplete Apposition (late- 429 (70163) 194 (736) acquired) QCA = quantitative coronary angiography RVD= reference vessel diameter MLD minimal lumen diameter DS percent diameter stenosisIQR = interquartile range SD = standard deviationFollow-up QCA results on stented lesions only (per lesion)

Subgroup Analyses

The HORIZONS AMI trial data were retrospectively evaluated for possible sex-based differences in baseline characteristics and clinical outcomes as well as for any interaction between treatment and sexgender The HORIZONS AMI trial was not designed or powered to study safety or effectiveness in sex-specific subgroups so these analyses were performed post hoc and are considered hypothesis generating

In the HORIZONS AMI population of patients randomized to TAXUS Express DES 17382257 (77) subjects were male and 5192257 (23) subjects were female The proportions in the Express BMS group were similar (76 male 24 female) According to the Nationwide Inpatient Sample (a large database of inpatient admissions from 1988 to 2004) men had almost 2 times the age-adjusted STEMI rate as women (men 624 women 376) The gender proportions enrolled in this trial are similar to other trials in the STEMI population23

In subjects treated with TAXUS Express DES 12-month TLR rates were 68 in females and 39 in males and Safety MACE rates were 101 in females and 75 in males In subjects treated with Express BMS 12-month TLR rates were 121 in females and 60 in males and Safety MACE rates were 123 in females and 66 in males (Table 9) Primary and secondary endpoint outcomes data stratified by gender are shown in Tables 9 and 10 HORIZONS AMI clinical results at 30 Days 1 Year 2 Year and 3 Year in male and female patients are reported in Table 11 Within the female group cardiac death was numerically higher through 30 days in

those treated with TAXUS Express versus bare metal Express but the numerical difference between groups narrowed over time Other trials of interventional treatment for AMI have shown female sex to be associated with higher mortality rates compared to men4 5 but differences appear to be largely explained by baseline risk factors such as BSA and angiographic disease severity Rates of reinfarction and stent thrombosis in females were numerically lower in


TAXUS Express DES versus bare metal Express at 30 days and through 3 years Formal interaction testing revealed no difference (at a significance level of p=O15) between males and females in treatment effect at any time point suggesting the conclusions of the overall study can be generalized for males and females

Table 9 HORIZONS AMI Primary Endpoints by Gender TAXUS Express Bare Metal Express

1 Year Ischemic TLR (N=2257) (N=749)

Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE

TAXUS Express (N=2257)

Bare Metal Express(N=749)

Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)

Safety MACE includes death reinfarction stroke or stent thrombosis

Table 10 HORIZONS AMI Secondary Endpoint by Gender Binary Restenosis at 13 TAXUS Express Bare Metal Express

Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)

Table 11 HORIZONS AMI Clinical Endpoints All TAXUS Express Male and Female Patients at 30 Days 1 Year 2 Year and 3 Year (Stent ITT Population)

TAXUS Express TAXUS Express Bare MetaI Bare Metal

Endpoint Male Patients Female Patients Express Male Express Female

(N=1738) (N=519) Patients Patients(N=569) (N=180)

30 DayNet Adverse Clinical 86 (149) 162 (84) 72 (41) 161 (29) Events

MACE 1 41(71) 74(38) 35(20) 78(14) MACE 2 (Safety 39(68) 66(34) 32(18) 78(14) MACE)3 Death 15(26) 41(21) 16(9) 28(5) - Cardiac 14 (24) 39 (20) 16 (9) 22 (4)

- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)

Death or reinfarction 29(51) 56(29) 28(16) 56 (10)

Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)

Ischemic TLR 18(32) 31(16) 21(12) 39(7) Stroke 06(10) 02(1) 02(1) 17 (3)



TAXUS Express TAXUS Express Bare MeBal Bare Metal Endpoint Male Patients Female Patients Express Ma e l Express Female

(N=1738) (N=519) Patients Patients (N=569) (N=180)

Major bleeding (nonshy 61 (105) 107 (55) 46 (26) 106 (19) CABG) Target Lesion stent 20(35) 28(14) 21(12) 45(8) thrombosis

1 Year

Net Adverse Clinical 133 (231) 237 (122) 137 (77) 245 (44) Events MACE 1 93(161) 148(76) 104(58) 190(34) MACE 2 (Safety 75 (129) 101 (52) 66 (37) 123 (22) MACE)

Death 29(50) 54(28) 28(16) 56(10) -Cardiac 18(32) 43(22) 23 (13) 39(7) -Noncardiac 11(18) 12(6) 05(3) 18(3)

Reinfarction 36 (62) 38 (19) 38 (21) 68 (12) - Q wave 21(36) 18(9) 16(9) 28(5) - Non Q wave 17(28) 22(11) 22(12) 40(7)

Death or reinfarction 62 (108) 86 (44) 60 (34) 100 (18) Ischemic TVR 50 (85) 89 (44) 72 (40) 138 (24) Ischemic TLR 39(66) 68(34) 60(33) 121(21) Stroke 09(16) 14(7) 04(2) 17(3) Major bleeding (nonshy 64 (110) 120 (61) 50 (28) 117 (21) CABG) Target Lesion stent 31 (52) 34 (17) 29 (16) 51 (9) thrombosis

2 Year Net Adverse Clinical 194 (333) 287 (147) 245 (135) 307 (55) Events MACE 12 159(271) 200(102) 214(117) 247(44) MACE 2 (Safety 105(179) 129(58) 105(58) 134(24) MACE) Death 37(63) 65(33) 51(28) 62(11)

- Cardiac 22(38) 43(22) 29(16) 45(8) - Noncardiac 15(25) 23(11) 23(12) 18(3)

Reinfarction 58 (96) 55 (27) 53 (29) 80 (14) - Q wave 33(55) 24 (12) 26(14) 24(6) - Non Q wave 28(46) 37(18) 28(15) 46(8)

Death or reinfarction 90 (153) 112 (57) 94 (52) 112 (20) Ischemic TVR 104 (173) 129 (63) 160 (86) 185 (32) Ischemic TLR 77 (128) 102 (50) 136 (73) 162 (28) Stroke 13 (22) 16 (8) 10 (5) 17 (3) Major bleeding (nonshy 65 (113) 124 (63) 54 (30) 123 (22) CABG) Target Lesion stent 41 (69) 42 (21) 36 (20) 57 (10) thrombosis 3 Year Net Adverse Clinical 223 (381) 319 (163) 267 (148) 319 (57) Events MACE 12 189 (321) 237 (120) 234 (129) 259 (46)



TAXUS Express TAXUSExpress Bare Metal Bare MetalEndpoint Male Patients Female Patients Express Male Express Female


MACE 2 (Safety 129(220) 158(80) 125(69) 140(25) MACE) Death 50 (85) 75 (38) 64 (35) 74 (13)

- Cardiac 28 (47) 47 (24) 36 (20) 45(8) - Noncardiac 23(38) 29(14) 28(15) 30(5)

Reinfarction 69(115) 72(35) 61(33) 80(14) - Q wave 37(62) 26(13) 26(14) 34(6) - Non Q wave 36(59) 53(25) 36(19) 46(8)

Death or reinfarction 112(190) 138(70) 114(63) 118(21) Ischemic TVR 117 (194) 146 (71) 171 (92) 192 (33) Ischemic TLR 87 (145) 117 (57) 145 (78) 169 (29) Stroke 16(26) 19(9) 13(7) 17(3) Major bleeding (nonshy 70 (120) 134 (68) 57 (32) 123 (22) CABG) Target Lesion stent 46 (77) 53 (26) 38 (21) 57 (10) thrombosis

Net Adverse Clinical Events includes MACE I and non-CABG related major bleeding 2 MACEl includes death reinfarction stroke or ischemic target vessel revascularization



XI PANEL MEETING RECOMMENDATION AND FDAS POST-PANEL ACTION

In accordance with the provisions of section 515(c)(2) of the act as amended by the Safe Medical Devices Act of 1990 this PMA was not referred to the Circulatory System Devices Panel an FDA advisory committee for review and recommendation because the information in the PMA did not require advisory panel input

XII CONCLUSIONS DRAWN FROM PRECLINICAL AND CLINICAL STUDIES

A Safety Conclusions

The adverse effects of the device are based on data collected in a clinical study conducted to support PMA supplement approval as described above The HORIZONS AMI trial showed that in STEMI patients compared to an otherwise identical Express BMS the TAXUS Express results in a similar rate of the composite of death reinfarction stroke or stent thrombosis at 1year Given the similarities between the ION Stent and the TAXUS Express2 stent and available supportive nonclinical and clinical data (see Section X above) the safety decision based on the HORIZONS AMI trial was considered applicable

B Effectiveness Conclusions

The HORIZONS AMI trial showed that in STEMI patients compared to an otherwise identical Express BMS the TAXUS Express results in reduced rates of ischemia-driven target lesion revascularization at 1 year and a lower rate of analysis segment binary angiographic restenosis at 13 months Given the similarities between the ION Stent and the TAXUS Express2 stent and available supportive nonclinical and clinical data (see Section X above) the effectiveness decision based on the HORIZONS AMI trial was considered applicable

C Overall Conclusions

The data in this application support the reasonable assurance of safety and effectiveness of this device when used in accordance with the indications for use

XIII CDRH DECISION

CDRH issued an approval order on February 22 2012


XIV APPROVAL SPECIFICATIONS

Directions for use See device labeling

Hazards to Health from Use of the Device See Indications Contraindications Warnings Precautions and Adverse Events in the device labeling

Post-approval Requirements and Restrictions See approval order

XV REFERENCES

1 Movahed M Ramaraj R Hashemzadeh M et al Rate of Acute ST-Elevation Myocardial Infarction in the United States from 1988 to 2004 (from the Nationwide Inpatient Sample) Am J Cardiol 20091045-8

2 GUSTO Investigators An International Randomized Trial Comparing Four Thrombolytic Strategies for Acute Myocardial Infarction N Engl J Med 1993 329 673-82

3 Lansky AJ Pietras C Costa RA et al Gender Differences in Outcomes After Primary Angioplasty Versus Primary Stenting With and Without Abciximab for Acute Myocardial Infarction Results of the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) Trial Circulation 2005 1111611-18


5 Berger JS Elliott L Gallup et al Sex Differences in Mortality Following Acute Coronary Syndrome JAMA 2009302(8)874-882

PMA P 100023SO1 FDA Summary of Safety and Effectiveness Data page 23

II INDICATIONS FOR USE

The ION Stent System is indicated for improving luminal diameter

for the treatment of de novo lesions in native coronary arteries 225 mm to 400 mm in diameter in lesions lt 34 mm in length or

undergoing primary angioplasty to treat acute ST-segment elevation in patients myocardial infarction true posterior myocardial infarction or presumed new left

bundle branch block with symptoms of acute myocardial infarction lasting gt 20 minutes and lt 12 hours in duration

III CONTRAINDICATIONS

Use of the ION Stent System is contraindicated in patients with

Known hypersensitivity to 316L stainless steel or platinum

Known hypersensitivity to paclitaxel or structurally-related compounds

Known hypersensitivity to the polymer or its individual components

Coronary Artery Stenting is contraindicated for use in a Patients who cannot receive recommended antiplatelet aridor anticoagulant therapy

0 Patients judged to have a lesion that prevents complete inflation of an angioplasty

balloon or proper placement of the stent or delivery device

IV WARNING AND PRECAUTIONS

The warnings and precautions can be found in the ION Paclitaxel-Eluting Coronary Stent

System Directions for Use (DFU)

V DEVICE DESCRIPTION

drug The ION Paclitaxel-Eluting Coronary Stent System is a device combination product

a device (Element Coronary Stent System) and a comprised of two regulated components

The componentsdrug product (a formulation of paclitaxel contained in a polymer coating) of the ION Paclitaxel-Eluting Coronary Stent System are identical to the and characteristics

Please refer to the original device description for additionalproduct approved in P100023 details The characteristics of the ION Stent System are described in Table 1

page PMA P 100023SO15 FDA Summary of Safety and Effectiveness Data 2



8 12 162024 283238


225 250 275 300 350 400


Thickness



38 mm)

Delivery System









































Design














Follow-Up



















within six weeks












calcification)
















angiographic subset
























(N=749)

1 Year 45 (98) 75 (54) -30 (-51 -09) 059 (043 083) 00018



(N=749) 1Year 81 (181) 80 (59) 01 (-21 24) 102 (076 136) 00075
















_____________________ (N=2257)A (N=749)













18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES









8 12 162024 283238


225 250 275 300 350 400


Thickness



38 mm)

Delivery System









































Design














Follow-Up



















within six weeks












calcification)
















angiographic subset
























(N=749)

1 Year 45 (98) 75 (54) -30 (-51 -09) 059 (043 083) 00018



(N=749) 1Year 81 (181) 80 (59) 01 (-21 24) 102 (076 136) 00075
















_____________________ (N=2257)A (N=749)













18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES
































Design














Follow-Up



















within six weeks












calcification)
















angiographic subset
























(N=749)

1 Year 45 (98) 75 (54) -30 (-51 -09) 059 (043 083) 00018



(N=749) 1Year 81 (181) 80 (59) 01 (-21 24) 102 (076 136) 00075
















_____________________ (N=2257)A (N=749)













18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES


















Follow-Up



















within six weeks












calcification)
















angiographic subset
























(N=749)

1 Year 45 (98) 75 (54) -30 (-51 -09) 059 (043 083) 00018



(N=749) 1Year 81 (181) 80 (59) 01 (-21 24) 102 (076 136) 00075
















_____________________ (N=2257)A (N=749)













18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES




















within six weeks












calcification)
















angiographic subset
























(N=749)

1 Year 45 (98) 75 (54) -30 (-51 -09) 059 (043 083) 00018



(N=749) 1Year 81 (181) 80 (59) 01 (-21 24) 102 (076 136) 00075
















_____________________ (N=2257)A (N=749)













18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES

















calcification)
















angiographic subset
























(N=749)

1 Year 45 (98) 75 (54) -30 (-51 -09) 059 (043 083) 00018



(N=749) 1Year 81 (181) 80 (59) 01 (-21 24) 102 (076 136) 00075
















_____________________ (N=2257)A (N=749)













18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES
















angiographic subset
























(N=749)

1 Year 45 (98) 75 (54) -30 (-51 -09) 059 (043 083) 00018



(N=749) 1Year 81 (181) 80 (59) 01 (-21 24) 102 (076 136) 00075
















_____________________ (N=2257)A (N=749)













18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES






















(N=749)

1 Year 45 (98) 75 (54) -30 (-51 -09) 059 (043 083) 00018



(N=749) 1Year 81 (181) 80 (59) 01 (-21 24) 102 (076 136) 00075
















_____________________ (N=2257)A (N=749)













18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES









_____________________ (N=2257)A (N=749)













18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES








18 18


15 15

-12 - 12

122

3 0 60 [0480 761 067[048093]

0= 0

0 3 6 9 12 15 18 21 24 27 30 33 36 0 3 9 12 15 18 21 4 27 30 33 3 6





15

12

(U

HR [95 C]=

3- 105 [084133]

p= 0660

0 3 6 9 12 15 18 21 24 27 30 33 36






6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES









6 shy

5

4shy

3 jrr _ - _ _

2- IHR [95 CI]=

084 [060 117]

p= 0311

0 33 0 3 6 9 12 15 18 21 24 27 30 33 36




5shy

4shy

C

HR [95 C9= 1 084 [054130]

p= 0424

0 3 6 9 12 15 18 21 24 27 30 33 36






6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES









6

5- r

0 r

4-shy

C3shy

2 - HR [95 C =

105 [076 146]

p= 0773

0 3 6 9 12 15 18 21 24 27 30 33 36





C)

0 0 HR [95 CI]= 0 1 110[1074 165]

ltt p= 0629

0 3 6 9 12 15 18 21 24 27 30 33 36










Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES













Subgroup Analyses









Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES










Male (N=2307) (N=1738)39 (66)

(N=569)60 (33)

Female (N=699) (N=519)

68 (34) (N=180)

121 (21)

S Safety MACE



Male (N=2307) (N=1738)75 (129)

(N=569)6-6 (37)

Female (N=699) (N=519)101 (52)

(N=180)123 (22)



Months (N=2257) (N=749)

(Per Lesion)

(N=1738) (N=569) Male (N=2307) 96 (83863) 226 (55243)

Female (N=699) (N=519)

115 (25218) (N=180)

236 (2189)







- Noncardiac 01(2) 02(1) 00(0) 06(1)

Reinfarction 16 (27) 20 (10) 16(9) 39(7)

- Q wave 12(21) 14(7) 12(7) 28(5)

- Non Q wave 04(7) 06(3) 04(2) 11(2)


Ischemic TVR 20 (35) 35 (18) 21 (12) 39(7)







1 Year





























XIII CDRH DECISION







XV REFERENCES











1 Year





























XIII CDRH DECISION







XV REFERENCES


























XIII CDRH DECISION







XV REFERENCES











XV REFERENCES







summary of safety and effectiveness data …...2012/02/22 · there are several other treatment...

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