(Orlando, 28th March,2008)

Randomized Comparison of Genous Stent Versus Chromium-Cobalt stent for Treatment

of STST--EElevationlevation Myocardial Infarction. 6-month Clinical, Angiographic and IVUS

Follow-up.GENIUS-STEMI trial.

Randomized Comparison of Genous Stent Versus Chromium-Cobalt stent for Treatment

of STST--EElevationlevation Myocardial Infarction. 6-month Clinical, Angiographic and IVUS

Follow-up.GENIUS-STEMI trial.

P. Červinka, M. Bystroň, R. Špaček, M. Kvašňák, J. JakabčinMasaryk hospital and University of J.E. Purkyne

Ústí nad Labem, Czech Republic

Presenter Disclosure Information

<Assoc. Prof . Pavel Červinka, MD, PhD, FESC, FSCAIAssoc. Prof . Pavel Červinka, MD, PhD, FESC, FSCAI

No relationships to disclose

GENIUS-STEMIGENIUS-STEMI

GENIUS-STEMIGENIUS-STEMI Acute coronary syndromes Acute coronary syndromes

(STEMI or UAP/NSTEMI )(STEMI or UAP/NSTEMI )

Plaque rupture/errosion + thrombosis

GENIUS-STEMIGENIUS-STEMI Concerns about DES thrombosis in Concerns about DES thrombosis in

patients with STEMIpatients with STEMI

GENIUS-STEMIGENIUS-STEMI EPC Capture Coating Technology EPC Capture Coating Technology (GENOUS(GENOUSTMTM stent) stent)

OrbusNeich has succesfully applied EPC capture technology to 316LOrbusNeich has succesfully applied EPC capture technology to 316L stainless steel stainless steel

Antibodies (murine monoclonal antihuman CD34) immobilizied on the stentAntibodies (murine monoclonal antihuman CD34) immobilizied on the stent surface are directed towards cell surface antigens on EPC surface are directed towards cell surface antigens on EPC

By recruiting the body´s own EPCs to the site of vascular injury/stent, anBy recruiting the body´s own EPCs to the site of vascular injury/stent, an acceleration of the normal endothelisation process would occuracceleration of the normal endothelisation process would occur

GENIUS-STEMIGENIUS-STEMI

Scanning electron micrographs (SEMs): 1 hourScanning electron micrographs (SEMs): 1 hour

almost complete cellular coveragealmost complete cellular coverage sparse cellular coveragesparse cellular coverage

EPC capture stent Bare stent

GENIUS-STEMIGENIUS-STEMI

The objective The objective of this trial was to assess the of this trial was to assess the feasibility and safety of the use of EPC capture feasibility and safety of the use of EPC capture stent for treatment of STEMI and comparison of stent for treatment of STEMI and comparison of 30-day 30-day and 6-month and 6-month outcome with chromium-outcome with chromium-

cobalt stents.cobalt stents.

The use of EPC The use of EPC capture capture stent may result in more stent may result in more rapid healing process and improve clinical rapid healing process and improve clinical

outcome.outcome.

PurposePurpose

8

Single center, Prospective, Randomized (envelope)Single center, Prospective, Randomized (envelope)

No sponsorNo sponsor

Ústí nad LabemÚstí nad Labem

Medical ethics committee of our institution approvedMedical ethics committee of our institution approved the study protocolthe study protocol

GENIUS-STEMIGENIUS-STEMI

GENIUS-STEMIGENIUS-STEMI MethodMethod

Between Between AugustAugust and December 2007, and December 2007, 100 100 consecutive consecutive patients with STEMI and single vessel patients with STEMI and single vessel disease were randomly assigned disease were randomly assigned (sealed envelope) (sealed envelope) to to

receive either EPC capture stent (N=50) (Genousreceive either EPC capture stent (N=50) (GenousTMTM stent stent)) or chromium-cobalt stent or chromium-cobalt stent ((N=50)N=50)

(either Driver(either DriverTM TM or Coroflex Blue or Coroflex BlueTMTM))

Dual antiplatelet treatment was administered for 30 days Dual antiplatelet treatment was administered for 30 days in both groups.in both groups.

AA 6-month clinical, angiographic and IVUS follow-ups 6-month clinical, angiographic and IVUS follow-ups were were assessed in both groups. assessed in both groups.

GENIUS-STEMIGENIUS-STEMI

EndpointsEndpoints

MACEs’MACEs’ (CV death, MI, clinically driven TLR) at 6 month FU

Late lumen loss at 6-month FU

Neointimal hyperplasia inside the stent at 6-month FU

GENIUS-STEMIGENIUS-STEMI

DefinitionsDefinitions

DeathsDeaths - cardiac or noncardiac

- undetermined causes reported as cardiac

Myocardial infarctionMyocardial infarction Q wave MI: new, pathological Q waves in≥2 contiguous leads with post-PCI increase

CK double the upper limit of normal and CK-MB>10% of CK level

Non-Q-wave MI: elevation of CK level to double the upper limit of normal,

CK-MB>10% of CK level and no Q-waves

TLRTLR – reinterventions inside the stent or within 5mm proximal or distal to the stent

Stent thrombosisStent thrombosis (according to the Academic Research Consorcium)

- early (0-30 days) - late (31-360days) - very late (>361 days)

- definite: ACS+angiographic or autopsy evidence of thrombus or occlusion

- probable: unexplained deaths within 30 days of the procedure or acute MI

involving the target-vessel teritory without angiography

- possible: all unexplained deaths>30 days after the procedure

GENIUS-STEMIGENIUS-STEMI

Continuous variables are expressed as the mean Continuous variables are expressed as the mean ±±SDSD

Categorical variables as percentagesCategorical variables as percentages

Continuous variables were compared by means of theContinuous variables were compared by means of the

Student´s Student´s t- t.t- t.

Categorical variables were compared by the means ofCategorical variables were compared by the means of

the the ΧΧ2 2 t.t.

A two-tailed value of p<0.05 was considered to be A two-tailed value of p<0.05 was considered to be

statistically significantstatistically significant

Statistical analysis (NCSSStatistical analysis (NCSS&&PASS)PASS)

GENIUS-STEMIGENIUS-STEMI

Study flow chartStudy flow chart

2007:2007: 400 P-PCI400 P-PCI

100 patients included100 patients included

(Randomization)

50 GenousTM 50 CrCo

ASA 100mg/day+clopidogrel 75mg/day 30 days; GPIIb/IIIa inhibitors

and thromboaspiration at the discretion of the physician

6-month clinical, angio and IVUS FU

GENIUS-STEMIGENIUS-STEMI Baseline demographicBaseline demographic, clinical and angiographic charcteristicsclinical and angiographic charcteristics

GENIUS-STEMIGENIUS-STEMI Procedural characteristicsProcedural characteristics

Genous Genous CCr-Co P valr-Co P valueue

N=50 N=50N=50 N=50

Stenosis (%) Stenosis (%) 5.2±4.5 3.9±3.7 5.2±4.5 3.9±3.7 NS NSMLD (mm) MLD (mm) 3.56±0.42 3.62±0.39 3.56±0.42 3.62±0.39 NSNSTTIMI flowIMI flow 0-1 (%) 0-1 (%) 0 0 0 0 NS NS 2 2 6 3 6 3 NS NS 3 3 94 97 NS 94 97 NSNumber of stents Number of stents 1.1.2020 1. 1.2626 NS NSLength of the stents (mm) Length of the stents (mm) 2200..4242 22. 22.3030 NS NSGGPP IIb/IIIa inhibitors (%) IIb/IIIa inhibitors (%) 32 22 NS32 22 NSThromboaspiration (%) Thromboaspiration (%) 17 25 17 25 NS NS

GENIUS-STEMIGENIUS-STEMI

6-month clinical outcome6-month clinical outcome

0

5

10

15

20

25

30

MACE CV Deaths MI TLR ST

P=0.03

P=NS

P=0.04

P=NSP=NS

(Non hierachical)

GenousTM CrCo

24

10

4 4 6 2

14

4 6 0

4 4

2 2

GENIUS-STEMIGENIUS-STEMI

6 month angio and IVUS data6 month angio and IVUS data

Genous Genous Cr-Co Cr-Co P valueP value

ANGIO DATAANGIO DATA N=44N=44 N=47 N=47 Late lumen loss (mm) 0.89±0.59 0.79±0.47 NSLate lumen loss (mm) 0.89±0.59 0.79±0.47 NS Restenosis (>50%) 20 13 NSRestenosis (>50%) 20 13 NS (QCA: Pie Medical Im)(QCA: Pie Medical Im)

IVUS N=41 N=42 mean in-stent NIH mean in-stent NIH (mm(mm33) ) 49.749.7±±4848 40.0±22.8 NS 40.0±22.8 NS (Volcano, pull back 0.5%mm/s)(Volcano, pull back 0.5%mm/s)

(QIVA Pie Medical Im)(QIVA Pie Medical Im)

GENIUS-STEMIGENIUS-STEMI Stent thrombosis in GenousStent thrombosis in GenousTMTM group group

P-PCI Day 30 Day 60

ASA

ASA+clopidogrel

32 48 52

ARC definition: ARC definition: 3x definite; 3x late

Patient Age TIMI Thrombus iGP IIb/IIa Vessel EF Stent Days Treatment Dual T Stát.Patient Age TIMI Thrombus iGP IIb/IIa Vessel EF Stent Days Treatment Dual T Stát.

J.J. 61 3 Y Y RCA 60 1; 2.75/23 48 dPOBA N AliveJ.J. 61 3 Y Y RCA 60 1; 2.75/23 48 dPOBA N Alive

P.U. 26 3 Y Y LAD 45 1; 3/23 32 dPCI+G Y AliveP.U. 26 3 Y Y LAD 45 1; 3/23 32 dPCI+G Y Alive

J.T. 47 2 Y Y RCA 52 2; 3.5/23+18 52 dPOBA N AliveJ.T. 47 2 Y Y RCA 52 2; 3.5/23+18 52 dPOBA N Alive

GENIUS-STEMIGENIUS-STEMI

Patient Age TIMI Thrombus iGP IIb/IIa Vessel EF Stent Days Treatment Dual T Stát.Patient Age TIMI Thrombus iGP IIb/IIa Vessel EF Stent Days Treatment Dual T Stát.

J.T. 47 2 Y Y RCA 52 2; 3.5/23+18 52 dPOBA N J.T. 47 2 Y Y RCA 52 2; 3.5/23+18 52 dPOBA N AliveAlive

GENIUS-STEMIGENIUS-STEMI SStudies with EPCs capture stenttudies with EPCs capture stent

6 M FU 12 M FU

MACE TLR

HEALING FIM HEALING II HEALING Iib Miglionico GENIUS e-HEALING CO et al. AMCR (N=16) (N=63) (N=99) (N=80) (N=100) (N=3196/5000) (N=120) (N=236))

LL 0.63mmNIH 52 mm3

LL 0.78mmNIH 31 mm3 AMI

LL 0.89mmNIH 50 mm3

LL 0.89mm

GENIUS-STEMIGENIUS-STEMI Conclusions:Conclusions:

The use of EPC capture stents in the setting of The use of EPC capture stents in the setting of STEMI is feasible and save. STEMI is feasible and save.

However, the rate of MACE at 6-month FU was However, the rate of MACE at 6-month FU was significantly higher in Genoussignificantly higher in GenousTMTM group when group when

compare to CrCo stents.compare to CrCo stents.

Warrisome is the rate of late stent thrombosis in Warrisome is the rate of late stent thrombosis in EPCs capture stent group.EPCs capture stent group.

Larger randomized trials are mandatory. Larger randomized trials are mandatory.

Caveats:Caveats:

Small, single center trialSmall, single center trial

Underpowered for MACEUnderpowered for MACE

No core labNo core lab