i2 2007 : late breaking clinical trialslong-term improvement in treatment targets group median ±se...

Ted Feldman, M.D., FSCAI, FACC

Angioplasty SummitApril 25-27th 2007

Seoul, Korea

Ted Feldman, M.D., FSCAI, FACC

Angioplasty SummitApril 25-27th 2007

Seoul, Korea

i2 2007 :Late Breaking Clinical Trials

i2 2007 :Late Breaking Clinical Trials

Ted Feldman MD, FACC, FSCAI

Disclosure Information

The following relationships exist:

Grant support: Abbott, Atritech, BSC, Cardiac Dimensions,Cordis, Evalve, St Jude

Consultant: BSC, Cardiac Dimensions, Cordis, Edwards, MyocorSpeaker: Boston Scientific

Off label use of products and investigational deviceswill be discussed in this presentation

Gibbons RJ. Abrams J. Chatterjee K. Daley J. et al. ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the ACC/AHA Task Force on practice guidelines (Committee on the Management of Patients With Chronic Stable Angina). Journal of the American College of Cardiology. 41(1):159-68, 2003

Smith SC Jr. Feldman TE. Hirshfeld JW Jr. et al. ACC/AHA/SCAI 2005 guideline update for percutaneous coronary intervention: ACC/AHA/SCAI Writing Committee to Update 2001 Guidelines for Percutaneous Coronary Intervention. Circulation. 113(7):e166-286, 2006

March 27, 2007

COURAGE Endpoints

RevascularizationDeath

Hosp for ACSDeath & non-fatal MI

0 1 2

.6.871.071.05

RR

Risk ratio(95% Cl)

Favors PCI

Favors Medical Management

18.5%19%Actual

21%16.4%Projected

OMTPCIDeath & MI

Incomplete Revascularization

59

41

31

69

0

10

20

30

40

50

60

70

1 2 or 3

%

Diseased vessels Number of stents

POBA 14.5% - DES 1.8%

21% Re-PCI due to incomplete revascularization?

Medicine 1138

PCI 1149

790

348

1497

Medicine + PCI vs… PCI + Medicine

40% started with minimal or no angina

30% crossed over

72% angina free at 5 years

ACE or ARB

Statin

Other anti-lipid

ASA

β-blocker

Ca-blocker

Nitrate

hypoglycemic

Long-Term Improvement in Treatment Targets Group Median ± SE Data

25%28.9 ±

0.17

149 ± 3.0339 ± 0.37

102 ± 1.22177 ± 1.4174 ± 0.33

130 ± 0.66

OMT

60 MonthsBaseline

42%29.2 ±

0.34

123 ± 4.1341 ± 0.6771 ± 1.33143 ± 1.7470 ± 0.81124 ± 0.81

PCI +OMT

25%28.7 ± 0.18143 ± 2.9639 ± 0.39100 ± 1.17172 ± 1.3774 ± 0.33131 ± 0.77

PCI +OMT

36%Moderate Activity (5x/wk)29.5 ± 0.31BMI Kg/M²131 ± 4.70TG mg/dL41 ± 0.75HDL mg/dL72 ± 1.21LDL mg/dL

140 ± 1.64Total Cholesterol mg/dL70 ± 0.65DBP

122 ± 0.92SBP

OMT

Treatment Targets

Anti-Anginal Therapy after 5 Years

5257

32

20

4042

0

10

20

30

40

50

60

Ca Blocker Nitrate PCI or CABG

%

PCIMedical Rx

CRUSADE RegistryCompliance with Medical Therapy in Patients with CAD

Patients with only one clinical follow up excludedPatients with only one clinical follow up excluded

71

46 43 3621

0

20

40

60

80

100

ASA BB Lipid ASA + BB ASA+BB+Lipid

Patie

nt C

ompl

ianc

e (%

)

71

46 43 3621

0

20

40

60

80

100

ASA BB Lipid ASA + BB ASA+BB+Lipid

Patie

nt C

ompl

ianc

e (%

)

Duke Databank for Cardiovascular Disease (1995-2002) AHA 2005

Selected populationRigorous optimal medical therapy (OMT) regimenIncomplete revascularization• BMS & POBA• procedure success 89%• device success 93%

Trend toward less mortality with PCIHigh rate of cross-over in OMT armReinforces existing guidelines

A Randomized Controlled Trial for the Prevention of Contrast Induced Nephropathy with Sodium

Bicarbonate in Persons Undergoing Coronary Angiography (MEENA)

Somjot S. Brar, MD

Kaiser PermanenteLos Angeles Medical Center

trialKaiser

Permanente

Study Flow353 Patients Undergoing Coronary Angiography, GFR ≤60

178 Patients 175 Patients

RSodium Chloride Sodium Bicarbonate

22 Excluded*6 Had early CABG3 Had Early PCI11 Had Incomplete Follow Up

Lab Data2 Had the Coronary Angiogram

Canceled

28 Excluded*8 Had Early CABG3 Had Early PCI16 Had Incomplete Follow Up

Lab Data1 Had the Coronary Angiogram

Canceled

156 Patients 147 Patients

* p=0.33

(1:1)

trialKaiser

Permanente

GFR & Creatinine Endpoints

02468

1012141618

GFR Creatinine

NaClNaHCO3

13.5 13.615.4 16.3

p=0.82

p=0.97In

cide

nce

of C

ontr

ast I

nduc

ed

Nep

hrop

athy

(%)

Primary Endpoint(≥ 25% Decrease in GFR)

Secondary Endpoint(≥ 25% Increase in Creatinine)

trialKaiser

Permanente

Conclusion

Hydration with Sodium Bicarbonate or Sodium Chloride in patients undergoing coronary angiography with a GFR ≤ 60 resulted in very similar rates of Contrast Induced Nephropathy.

trialKaiser

Permanente

Disclosures

DISCLOSURE INFORMATION:The following relationships exist related to this presentation:None

UNLABELED/UNAPPROVED USE:The following products are not labeled for the use under discussion or are still investigational:Sodium Bicarbonate for the Prevention of Contrast Induced Nephropathy

DISCLOSURE INFORMATION:The following relationships exist related to this presentation:None

UNLABELED/UNAPPROVED USE:The following products are not labeled for the use under discussion or are still investigational:Sodium Bicarbonate for the Prevention of Contrast Induced Nephropathy

Low REsponsiveness to CLOpidogrel and

Sirolimus- or Paclitaxel-Eluting StEnt

Thrombosis (RE-CLOSE) Trial

David Antoniucci, MD, ACC 2007

Department of Cardiology, Careggi Hospital, Florence, Italy

Investigators: Abbate R (PI), Antoniucci D (PI), Buonamici P, Gensini GF, Gori AG, Marcucci R, Migliorini A, Moschi G,

Paniccia R, Santini A

Primary End Point

8.6

2.3

0123456789

10

Responders Non-Responders

% a

t 6 M

onth

s

4.8

0.6

0123456789

10

Responders Non-Responders

%

Definite/Probable Thrombosis

Late StentThrombosis

P<.001

P<.001

n=699

n=105

Long-Term Safety of DES in Off-Label Use:

Results of the MATRIX Registry

George D. Dangas, MD, PhD, FACCOn Behalf of the Matrix Investigators

MATRIX: Goals and DesignProspective single arm study initiated in 2004 as a 3,500 patient trial under an investigator-initiated IDE

Both on- and off-label SES use

Clinical follow-up at 1 month, 6 months, 1 year and 2 years thus far

MATRIX Registry

Procedural Characteristics

MATRIX Registry

95.6%Procedure success

16.0%Unfractionated heparin

2.0±1.2No. of stents per procedure

1.1±0.5No. of stents per lesion

8.1%IIb/IIIa inhibitors administered

84.9%Bivalirudin used

98.5%Device success (N=2608 Lesions)

N = 1,522 patients

89%

93%

On-Label Use of Cypher StentThe CYPHER Sirolimus-eluting Coronary Stent is indicated in patients with symptomatic ischemic disease due to discrete de novo lesions of length < 30 mm in native coronary arteries with a reference vessel diameter of > 2.5 to < 3.5 mm (http://www.fda.gov/cdrh/PDF2/p020026c.pdf).On-label definition in MATRIX: De novo lesion; 1 lesion; 1 vessel; Lesion length < 30mm; RVD 2.5-3.5mm; Also excluding:• Diffuse disease• Multivessel PCI; PCI with 3 of more SES• Use of rotablator, atherectomy or laser• Use of thrombectomy or intracoronary thrombus• Acute ST elevation MI within 72 hours before the procedure • ACS with positive CKMB prePCI• Ostial lesions• Bifurcation lesions• Chronic occlusions, baseline TIMI flow 0 or 1 • Vein grafts, LIMA/RIMA, radial or GEA grafts• Angioplasty restenosis or in-stent restenosis• Severe calcification; Severe tortuosity

MATRIX Registry

14% Of Patients in MATRIX w/o any of above14% Of Patients in MATRIX w/o any of above

Stent Thrombosis (K-M analysis)

MATRIX Registry

0.5 0.50.5 0.50.6

0.4

1.1

0.6

0.0

0.5

1.0

1.5

30 days 6 months 1 year 2 year

On-label Off-label%

* Stent thrombosis included the definite and probable thromboses by ARC

P=0.829P=0.826 P=0.826

P=0.649

5+3 7+40+10+10+10+1 5+32+3

Prediction of 2-Year Adverse OutcomesMultivariate Predictors Using Cox Model

MATRIX Registry

0.09770.99 - 1.071.03Lesion length, mm

0.01481.34 - 14.794.45Chronic Renal Insufficiency

Definite or probable stent thrombosis (12 events)

<0.00011.05 - 1.131.09Age, y

1.11 - 13.08

1.04 - 1.18

1.58 - 28.34

1.94 - 8.38

95% CI

0.0334

0.0028

0.0099

0.0002

p

4.03DM

6.69Dialysis

1.11Age, y

Cardiac death (11 events)

Death (32 events)

3.81DM

Hazard Ratio2-Year Events

Candidate predictors included on-label use, ACS, multivessel/stent PCI, RVD, clopidogrel.

Prediction of 2-Year Adverse OutcomesMultivariate Predictors Using Cox Model

MATRIX Registry

0.00511.18 to 2.521.72DM

0.02730.27 to 0.930.50Male0.03251.00 to 1.061.03Age, y

0.96 to 0.990.26 to 1.10

1.01 to 1.061.42 to 5.64

95% CI

0.01560.0870

0.00240.0031

p

2.83Renal insufficiency1.03Lesion length, mm

0.53On-labelTVR (107 events)

MI (43 events)

0.98Age, y

Hazard Ratio2-Year Events

Candidate predictors included on-label use, ACS, multivessel/stent PCI, RVD, clopidogrel.

MATRIX - Conclusions

In Matrix, we found:Low frequency of early and late adverse events considering the complexity of patients and lesions treated• 2-year death 3.3%, death/MI 6.8%, death/MI/TVR 15.6%

2-year stent thrombosis rate 1.1% • ARC definite/probable definitions • Independent event adjudication

Similar mortality in on- vs off-label use• MI and TVR were higher with off-label application • Independent predictors of mortality, stent thrombosis and MI included

baseline patient and lesion characteristics (i.e. Age, DM, Renal failure, lesion length) as opposed to off-label application and procedure factors.

In 1,522 patients with complex CAD treated with SES, off-label use of SES using a strict definition was evident in 86% of patients.

In 1,522 patients with complex CAD treated with SES, off-label use of SES using a strict definition was evident in 86% of patients.

MATRIX Registry

Clinical Evaluation of the Abbott Vascular BVS Bioabsorbable Everolimus Eluting Coronary Stent System in the Treatment of Subjects with de novo

Native Coronary Artery Lesions

Patrick Serruys, MD, PhDCo-Principal Investigator of the ABSORB Trial

Bioabsorbable Polymer

Everolimus/PLA Matrix CoatingThin coating layerAmorphous (non-crystalline)1:1 ratio of Everolimus/PLA matrixConformal CoatingControlled drug release

PLA Stent BackboneHighly crystallineProvides stent integrityProcessed for increased radial strength

Product currently in development at Abbott Vascular. Not available for sale.

Polymer backbone

Drug/polymer matrix

QCA/IVUS Patient inclusion

30 patients

26 patients

n = 4 excluded*

3 bailout stenting

1 device failure

6 months QCA

24 patients

n = 2 IVUS not analyzable

6 months IVUS

* Per treatment evaluable population. Four patients were excluded who received a non-BVS bailout stent, including one patient who did not receive a BVS stent at the target lesion.

Product currently in development at Abbott Vascular. Not available for sale.

What is Contributing to Late Loss?

∆ Vessel Area (mm2) = -0.29 (-1.9%)

∆ Stent Area (mm2) = -0.14 (-2.0%)

∆ Lumen Area (mm2) = -2.12 (-29.4%)

NIH Area (mm2) = 1.98

% VO = 28.1%

∆ Vessel Area (mm2) = 0.19 (+1.2%)

∆ Stent Area (mm2) = -0.02 (-0.3%)

∆ Lumen Area (mm2) = -0.51 (-7.2%)

NIH Area (mm2) = 0.50

% VO = 8.0%

∆ Vessel Area (mm2) = -0.06 (-0.4%)

∆ Stent Area (mm2) = -0.71 (-11.7%)

∆ Lumen Area (mm2) = -1.01 (-16.6%)

NIH Area (mm2) = 0.30

% VO = 5.5%

Late Loss = 0.87mm Late Loss = 0.10mm Late Loss = 0.44mm

SPIRIT-FirstML Vision Stent

SPIRIT-FirstXience V Stent

ABSORBBVS Stent

Leif Thuesen, Henning Kelbæk, Jens F. Lassen, Christian Juhl Terkelsen, Peter Clemmensen, Steffen Helqvist, Lene Kløvgaard, Anne Kaltoft, Lars Krusell, Kari Saunamäki, Erik Jørgensen, Hans E. Bøtker, Jan Ravkilde, Klaus Kofoed, Hans

Henrik T. Hansen, Evald H. Christiansen, Thomas Engstrøm, Lars Køber

Randomized Comparison of the Effect of Distal Protection and Drug Eluting Stent versus Bare Metal Stent Implantation during Percutaneous

Coronary Intervention for ST-elevation Myocardial Infarction

The DEDICATION study

Rigshospitalet, Copenhagen

Aarhus University Hospital, Skejby

Denmark

DEDICATION

Patients with Acute ST-elevation Myocardial Infarctionn=626

Randomization

Primary PCI+ Distal Protection

(n: 312)

Primary PCI- Distal Protection

(n: 314)

ECG ST-resolution at 30-90 min

Post procedure TIMI flowWall motion index at dischargeCardiac biomarker releaseMajor adverse cardiac and cerebral events at 30 days

Secondary endpoints

Flow Chart

Primary end point

DEDICATIONPrimary Endpoint: ST-Segment Resolution

Distal protection

Conventional treatment

76%

72%

Log Rank, P=0.27

0

60

40

20

80

100 %

-

Time from 1.wire (minutes)

Ted Feldman, M.D., FSCAI, FACCfor the EVEREST Investigators

ACC -New OrleansMarch 26th 2007

Ted Feldman, M.D., FSCAI, FACCfor the EVEREST Investigators

ACC -New OrleansMarch 26th 2007

Significant Reduction in Mitral Regurgitation Twelve Months Following Percutaneous Mitral Valve Repair:

Initial Experience With the MitraClip Device

Significant Reduction in Mitral Regurgitation Twelve Months Following Percutaneous Mitral Valve Repair:

Initial Experience With the MitraClip Device

EVEREST Registry

Percutaneous Mitral Repair

Caution: Investigational Device. Limited by Federal (US) Law to Investigational Use

Event Free Clinical Success Kaplan-MeierPatients with Acute Procedural Success

n = 79

Freedom from death, mitral valve surgery, & MR>2

99% 97% 97% 97% 97%100%

90% 87%86% 86% 86% 85%

67%68%68%68%72%

85%

0%

20%

40%

60%

80%

100%

0 6 12 18 24 30 36 42

Time (months)

Prob

abili

ty o

f Eve

nt F

ree

Clin

ical

Suc

cess

Freedom From Death

Freedom From Surgery

Freedom From Death, Surgery or MR >2+

n = Reached Endpoint

68 61 4279 36 28

EVOLUTION (Clinical EValuation Of the Edwards Lifesciences PercUTaneous MItral

AnnulOplasty System for the treatment of Mitral RegurgitatioN)

Interim Results and Case Experience

Caution: Investigational Device. Limited by Federal (US) Law to Investigational Use. Not offered in the United States

Karl Heinz Kuck, MD, Hamburg, Germany

The MONARC system Delayed Release-in situ

EVOLUTION study interim performance data

0

1

2

3

4

Baseline 30 Days 90 Days 180 Days

Mea

n M

R Va

lue

Mean MR Reduction over Time

Sustained Device Tension

Active Device Foreshortening

(6 Weeks)

-Baseline Grade 3-4+-Baseline Grade 2-4+

1.6

3.4

1.4

2.7

(n = 22)

(n = 7)

(n = 42)

(n = 13)

(n = 14)

(n = 15)

(n = 30) (n = 27)

Echo Core Lab data

2.62.3

2.1 2.0