AMC TRIAS HR Pilot RdW - CMS · AMC-UVA Amsterdam Interventional Cardiology TRIAS HR Pilot Study...

AMCAMC--UVAUVA Amsterdam Amsterdam InterventionalInterventional CardiologyCardiology

TRIAS HR Pilot Study

RCT comparing Genous EPC capturing stent

with Taxus Paclitaxel eluting stent

Robbert J de Winter MD PhD FESC

Academic Medical CenterUniversity of Amsterdam

The Netherlands

Late Breaking Clinical Trials Late Breaking Clinical Trials TCT, October 22TCT, October 22ndnd 2007, 2007, Washington, USAWashington, USA


Disclosures Dr. R.J. de WinterDisclosures Dr. R.J. de Winter

Grant and / or Research SupportOrbusNeich

ConsultingOrbusNeich, Merck-Sharp Dome

Speaker’s BureauLilly

c r e a t e

��

��

� ��

� ��


IntroductionIntroductionTRIAS HR Pilot studyTRIAS HR Pilot study

c r e a t e

��

• Accelerated Healing

• Protects Against Thrombus

• Minimizes Restenosis

• Improved Safety Profile Over Current

DES


ObjectiveObjective

To compare the feasibility and efficacy of the To compare the feasibility and efficacy of the GenousGenous EPCEPC--attracting stent with the attracting stent with the TaxusTaxuspaclitaxelpaclitaxel--eluting stent in the treatment of eluting stent in the treatment of coronary artery stenosis in patients / lesions coronary artery stenosis in patients / lesions with high risk of restenosis. with high risk of restenosis.

TRIAS HR Pilot studyTRIAS HR Pilot study



Restricted DES use in selected patients with Restricted DES use in selected patients with high risk of restenosis, BMS in patients with high risk of restenosis, BMS in patients with low risk of restenosislow risk of restenosis

High risk of restenosis is defined as:High risk of restenosis is defined as:

�� Lesion Lesion �� 23 mm in length23 mm in length�� Lesions in vessels Lesions in vessels �� 2.8 mm in diameter2.8 mm in diameter�� Any lesion in diabetic patientsAny lesion in diabetic patients�� Chronic total occlusionChronic total occlusion

DesignDesign


High risk of restenosisHigh risk of restenosis

Genous StentGenous Stent TaxusTaxus stentstent

Statins 1 wkStatins 1 wk

AngiographicAngiographicSub studySub study

Target vessel failureTarget vessel failure

NonNon--inferiorityinferiority

Clopidogrel 6Clopidogrel 6Clopidogrel 1 mClopidogrel 1 m

12 m clinical FU12 m clinical FU 12 m clinical FU12 m clinical FU

®®

5 y clinical FU5 y clinical FU 5 y clinical FU5 y clinical FUDeath / MIDeath / MI

SuperioritySuperiority


Lesion Lesion �� 23 mm23 mmRVD RVD �� 2.8mm2.8mmDiabetesDiabetesCTOCTO

DesignDesign



�� SingleSingle--center, prospective, randomized, singlecenter, prospective, randomized, single--blindblind

studystudy

�� Inclusion period: February 2006 Inclusion period: February 2006 -- April 2007April 2007

�� Patients with de novo coronary artery lesionPatients with de novo coronary artery lesion

with a high risk of restenosiswith a high risk of restenosis

�� Dual antiDual anti--platelet therapy for at least 1 month after platelet therapy for at least 1 month after

GenousGenous and 6 months after and 6 months after TaxusTaxus stentstent

�� 30 days, 6 months and 1, 2, 3, 4, 5 year clinical FU30 days, 6 months and 1, 2, 3, 4, 5 year clinical FU√√ telephone contact telephone contact

√√ clinical records and discharge lettersclinical records and discharge letters

MethodsMethods



�� Clinically stable patients undergoing a PCI for a Clinically stable patients undergoing a PCI for a

native, de novo, coronary artery native, de novo, coronary artery lesion(slesion(s))

�� Target lesion considered high risk of restenosisTarget lesion considered high risk of restenosis√√ Lesion Lesion �� 23 mm23 mm

√√ RVD RVD �� 2.8mm2.8mm

√√ DiabetesDiabetes

√√ CTOCTO

�� All patients on statin therapy All patients on statin therapy �� 7 days 7 days

Inclusion criteriaInclusion criteria


TRIAS HR Pilot studyTRIAS HR Pilot study�� < 18 years< 18 years

�� ST elevation myocardial infarctionST elevation myocardial infarction

�� Current unstable arrhythmiasCurrent unstable arrhythmias

�� Recipient of a heart transplant or any other organ transplant oRecipient of a heart transplant or any other organ transplant or is on a waitingr is on a waiting

list for any organ transplantlist for any organ transplant

�� Scheduled to receive chemotherapy or radiation therapy within 3Scheduled to receive chemotherapy or radiation therapy within 30 days prior or0 days prior or

after the procedureafter the procedure

�� Receiving immuneReceiving immune--suppression therapy or has known immunosuppressive or suppression therapy or has known immunosuppressive or

autoimmune disease (e.g. human immunodeficiency virus, systeautoimmune disease (e.g. human immunodeficiency virus, systemic lupus mic lupus

erythematosuserythematosus atcatc.).)

�� Hypersensitivity or contraindication to aspirin, either heparinHypersensitivity or contraindication to aspirin, either heparin or or bivalirudinbivalirudin, ,

clopidogrel, clopidogrel, paclitaxelpaclitaxel, cobalt, chromium, nickel, tungsten, acrylic and , cobalt, chromium, nickel, tungsten, acrylic and fluorofluoro--

polymers or contrast sensitivity that can not be adequately polymers or contrast sensitivity that can not be adequately prepre--medicatedmedicated

�� Planned elective surgery within the first 6 months after the prPlanned elective surgery within the first 6 months after the procedure that will ocedure that will

require discontinuing either aspirin or clopidogrelrequire discontinuing either aspirin or clopidogrel

Exclusion criteriaExclusion criteria


TRIAS HR Pilot studyTRIAS HR Pilot study�� Platelet count < 100,000 or > 700,000 cells/ mm3, a WBC < 3,000Platelet count < 100,000 or > 700,000 cells/ mm3, a WBC < 3,000 cells/ mm3, cells/ mm3,

or liver disease (including laboratory evidence of hepatitisor liver disease (including laboratory evidence of hepatitis))

�� Severe renal insufficiencySevere renal insufficiency

�� Coronary anatomy unsuited for coronary revascularization Coronary anatomy unsuited for coronary revascularization

�� CVA (hemorrhagic / ischemic) or TIA of any etiology within 30 dCVA (hemorrhagic / ischemic) or TIA of any etiology within 30 days of ays of

randomizationrandomization

�� Evidence of active abnormal bleeding within 30 days of randomizEvidence of active abnormal bleeding within 30 days of randomization ation

�� Severe hypertensionSevere hypertension

�� Previous participation in this study or any other trial within Previous participation in this study or any other trial within the previous 30 daysthe previous 30 days

�� Circumstances that prevent followCircumstances that prevent follow--up up

�� Women who are pregnant or who are of childbearing potential whoWomen who are pregnant or who are of childbearing potential who do not use do not use

adequate contraception. adequate contraception.

�� Criteria related to the EPCCriteria related to the EPC--attracting stent:attracting stent:

�� Patients who have previously received Patients who have previously received murinemurine therapeutic antibodies and therapeutic antibodies and

exhibited sensitization through the production of Human Antiexhibited sensitization through the production of Human Anti--MurineMurine Ab(HAMAAb(HAMA).).

Exclusion criteriaExclusion criteria



RandomizationRandomization�� Randomization target lesion between Randomization target lesion between GenousGenous stent stent

and and TaxusTaxus stentstentMultiple lesionsMultiple lesions

�� High risk lesions treated according to the randomizedHigh risk lesions treated according to the randomized

treatment assignment treatment assignment

�� Low risk of restenosis lesions in nonLow risk of restenosis lesions in non--target vessels target vessels

treated with BMStreated with BMS

Bailout procedureBailout procedure

�� Use bailoutUse bailout--stent according to randomized treatment stent according to randomized treatment

assignmentassignment

Treatment strategyTreatment strategy



Target vessel failureTarget vessel failure at 1 year:at 1 year:

�� Cardiac deathCardiac death

�� Myocardial infarction Myocardial infarction (unless documented to arise from the non(unless documented to arise from the non--treated coronary artery)treated coronary artery)

�� Repeat revascularization of the treated vesselRepeat revascularization of the treated vessel

Main long term endpoint Main long term endpoint at 5 years:at 5 years:

�� Death or MIDeath or MI

Primary endpointPrimary endpoint



�� Procedural success, defined as a less than 20% Procedural success, defined as a less than 20%

residual stenosis and TIMI 3 flow post PCIresidual stenosis and TIMI 3 flow post PCI

Within 1, 2 , 3, 4, and 5 years:Within 1, 2 , 3, 4, and 5 years:

�� Target Vessel FailureTarget Vessel Failure

�� Target Lesion FailureTarget Lesion Failure

�� Target Vessel Revascularization Target Vessel Revascularization

�� Target Lesion Revascularization Target Lesion Revascularization

�� Hospitalization for Acute Coronary SyndromeHospitalization for Acute Coronary Syndrome

Secondary endpointsSecondary endpoints


(98%)(98%)(96%)(96%)

(3%)(3%)(26%)(26%)(41%)(41%)

(15%)(15%)(85%)(85%)

(32%)(32%)(64%)(64%)(53%)(53%)(56%)(56%)(27%)(27%)

((74%)74%)±± 10 y10 y

NsNsNsNs

NsNsNsNsNsNs

NsNsNsNs

NsNsNsNsNsNsNsNs0.0250.025

NsNsNsNs

(100%)(100%)(95%)(95%)

(3%)(3%)(26%)(26%)(38%)(38%)

(18%)(18%)(82%)(82%)

(33)%(33)%(53%)(53%)(63%)(63%)(46%)(46%)(14%)(14%)

(73%)(73%)±± 10 y10 y

98989393

3325253737

18188080

32325252626245451414

72726262

33Previous CABGPrevious CABG2525Previous PCIPrevious PCI3939Previous MIPrevious MI

1414Unstable anginaUnstable angina8181Stable anginaStable angina

9393StatinsStatins9191AspirinAspirin

3030Current smokingCurrent smoking6161Family history of CADFamily history of CAD5050HypercholesterolemiaHypercholesterolemia5353HypertensionHypertension2626DiabetesDiabetes

Risk factorsRisk factors7070MaleMale6363AgeAge

TaxusN = 95

GenousN = 98

P-value

TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResultsBaseline characteristicsBaseline characteristics


(23%)(23%)(37%)(37%)((1% )1% )(39%)(39%)

(20%)(20%)

(80%)(80%)

(24(24%)%)

(42%)(42%)(42%)(42%)(12%)(12%)((2% )2% )

NsNs

0.0040.004

NsNs

NsNs

NsNs

(26%)(26%)(40%)(40%)( 1( 1%)%)(34%)(34%)

( 7( 7%)%)

(83%)(83%)

(32%)(32%)

(47%)(47%)(45%)(45%)( 8%)( 8%)( 0%)( 0%)

31314848

114141

99

101101

3939

575754541010

00

11LMLM4949RCARCA

Treated vesselTreated vessel

2525Vessels Vessels �� 2.8 mm2.8 mm

2929CXCX4646LADLAD

100100Lesions Lesions �� 23 mm23 mm

3030Total chronic occlusionTotal chronic occlusion

5252CC5252B2B21515B1B1

22AAType of lesionType of lesion

TaxusN = 125

GenousN = 121

P-value

TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResultsLesion characteristicsLesion characteristics


NsNs±± 101025.425.4±± 121226.826.8Lesion length, mmLesion length, mm

NsNs±± 0.50.53.23.2±± 0.30.33.23.2Ref vessel diameter, mmRef vessel diameter, mm

(99%)(99%)

±± 3.53.5

(70%)(70%)

±± 2.52.5

±± 1212

±± 0.480.48

(89(89%)%)

(66%)(66%)

NsNs

NsNs

NsNs

NsNs

NsNs

NsNs

NsNs

NsNs

(98%)(98%)

±± 3.63.6

(73%)(73%)

±± 2.62.6

±± 14.314.3

±± 0.540.54

(89%)(89%)

(61%)(61%)

119119

18.618.6

8888

1313

31.731.7

1.21.2

108108

7474

124124Procedural success Procedural success

1818Max Max AtmAtm post dilatationpost dilatation

8888Post dilatationPost dilatation

1414Max Max AtmAtm stent placementstent placement

30.730.7Total stent length, mmTotal stent length, mm

1.21.2Stents per lesionStents per lesion

111111PrePre--dilatationdilatation

8383PrePre--procedure TIMI 3 flowprocedure TIMI 3 flow

TaxusN = 125

GenousN = 121

P-value

TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResultsProcedural characteristicsProcedural characteristics


GenousGenous•• wirewire perforationperforation resultingresulting in in pericardial effusionpericardial effusion

•• stentstent loss in RCA, loss in RCA, afterafter dilatationdilatation TIMI 2 TIMI 2 flowflow

•• nono--reflowreflow phenomenonphenomenon; ; afterafter additionaladditional dilatationsdilatationsTIMI 3 TIMI 3 flowflow; ; maxmax CKCK--MB 145 MB 145 µµg/Lg/L

TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResultsProcedural complicationsProcedural complications

TaxusTaxus•• wire perforation resulting in pericardial effusionwire perforation resulting in pericardial effusion•• major major extravasationextravasation of contrastof contrast


NsNs(2.2%)(2.2%)22(1.1%)(1.1%)11Stent thrombosisStent thrombosis

(6.5%)(6.5%)

(2.2%)(2.2%)(7.6%)(7.6%)

(2.2%)(2.2%)

(1.1%)(1.1%)

(1.1%)(1.1%)

(1.1%)(1.1%)

00

11000011

11

000000

NsNs00TVR remoteTVR remote

00CABGCABG

NsNs22TLRTLR

0.050.0566Non TVR Non TVR

0.0280.02877Repeat PCIRepeat PCI

00CardiacCardiac00NonNon--CardiacCardiac

22

00

NsNsMIMI

DeathDeath

TaxusN=92

GenousN=95

P-value

TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResults3030--Day clinical outcomeDay clinical outcome


Genous StentGenous StentN = 95N = 95

TaxusTaxus stentstentN = 92N = 92

TRIAS HR Pilot studyTRIAS HR Pilot study ResultsResults66--month clinical outcomemonth clinical outcome

On Clopidogrel:On Clopidogrel: 42 (44 %)42 (44 %) 68 (73 %)68 (73 %)

Anginal complaints:Anginal complaints:No anginaNo angina 74 (78 %)74 (78 %) 79 (86 %)79 (86 %)CCS 1CCS 1 7 (7.3 %)7 (7.3 %) 4 (4.3 %)4 (4.3 %)CCS 2CCS 2 11 (12 %)11 (12 %) 5 (5.4 %)5 (5.4 %)CCS 3CCS 3 2 (2.1 %)2 (2.1 %) 3 (3.3 %)3 (3.3 %)CCS 4CCS 4 1 (1.1 %)1 (1.1 %) 1 (1.1 %)1 (1.1 %)

Mean followMean follow--up @ 192 daysup @ 192 days


Repeat PCIRepeat PCI

(1.1%)(1.1%)

(14%)(14%)

(4.3%)(4.3%)

(3.2%)(3.2%)

(2.1%)(2.1%)

(3.2%)(3.2%)

(5.3%)(5.3%)

(1.1%)(1.1%)

22

3300

55

11

00

00TVR remoteTVR remote

NsNs11CABGCABG

NsNs44TLRTLR

0.0070.0071313Non TVR Non TVR

33

00

NsNsMIMI

DeathDeath

TaxusN=92

GenousN=95

P-value



Repeat PCIRepeat PCI

(5.4%)(5.4%)

(1.1%)(1.1%)

(4.3%)(4.3%)

(3.2%)(3.2%)

(8.4%)(8.4%)

(2.1%)(2.1%)

(5.3%)(5.3%)

(1.1%)(1.1%)

88

22

00

55

11

00

NsNs55Target vessel failureTarget vessel failure

00TVR remoteTVR remote

NsNs11CABGCABG

NsNs44TLRTLR

33

00

NsNsMIMI

DeathDeath

TaxusN=92

GenousN=95

P-value




Stent thrombosis:Stent thrombosis:

GenousGenous@ 6 hours @ 6 hours TLR, no MITLR, no MI

TaxusTaxus@ 24 hours@ 24 hours MI, TLRMI, TLR@ 10 days @ 10 days MI, TLRMI, TLR@ 155 days @ 155 days MI, TLRMI, TLR

�� All All angiographicallyangiographically documented stent thrombosisdocumented stent thrombosis�� All on dual All on dual antiplateletantiplatelet therapy at time of STtherapy at time of ST


Randomized study comparing the Genous stent and first generation DES is feasible in patients treated with PCI for high risk restenosis lesions

Similar clinical outcomes at 6-months in this (underpowered) pilot study in patients treated with PCI for high risk restenosis lesions between the GenousEPC-capturing stent and the Taxus paclitaxel eluting stent

The pilot study is followed by a large multi-center study

TRIAS HR Pilot studyTRIAS HR Pilot study ConclusionsConclusions

AMC Amsterdam AMC Amsterdam InterventionalInterventional CardiologyCardiology

AMC AMC GenousGenous experienceexperience

Interventional operators

K.T. Koch

J.P. Henriques

R.J. vd Schaaf

J. Baan

M.M .Vis

J.J. piek

de Winter RJ Drug eluting stent summit, TCT 2007de Winter RJ Drug eluting stent summit, TCT 2007

Data collection and statistics

J.G.P. Tijssen

M.A. Beijk

C.J. Verouden

M. Klomp

Cathlab nursing staff

M.G. Meesterman

F. Hoekstra

N. van Daalen

Research nursing staff

M. Klees

E. Schoenhagen

W. Rohling

Database manager

I. vd Wal

Project management

L. Peeters

THANK YOU

AMC TRIAS HR Pilot RdW - CMS · AMC-UVA Amsterdam Interventional Cardiology TRIAS HR Pilot Study...

Documents

Transcript of AMC TRIAS HR Pilot RdW - CMS · AMC-UVA Amsterdam Interventional Cardiology TRIAS HR Pilot Study...