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