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2007, The Year in PCI2007, The Year in PCI
Asad Pathan Asad Pathan
FACC FSCAIFACC FSCAI
March 15th, 2008
2007, The Year in PCI2007, The Year in PCI DESDES
– RegistriesRegistries– New stentsNew stents
AnticaogulantsAnticaogulants– BivalirudinBivalirudin
Stable CADStable CAD– COURAGE trialCOURAGE trial
AMIAMI– Technique/aspirationTechnique/aspiration
New DevicesNew Devices– Drug Eluting balloonDrug Eluting balloon
Drug Eluting StentsDrug Eluting Stents
DES vs BMSDES vs BMSRecent Registry Data Recent Registry Data
0.6
5.34.5
6.4
0.8
7.9
3.7
7.9
0
2
4
6
8
10
12
14
Death MI TLR Total ST
% o
f ev
ent
Western Denmark Clinical endpoints to 2 years (unadjusted)
NS
P=0.004
NS
P<0.0001
DES ( N=8847)
BMS (N=3548)
Jensen TCT 2007
0.2
5.3
2.02.4
0.04
7.90
1.002.20
0
2
4
6
8
10
12
14
Death MI TLR* Definite ST
% o
f ev
ent
DES ( N=8847)
BMS (N=3548)
Western Denmark Clinical endpoints >1 to 2 years
P=0.02
P<0.0001
P=0.0019
P<0.001
*2 yr cumulativeAdjusted P values
Jensen TCT 2007
9.3
7.4
5.24.3
10.510.7
5.76.1
0
2
4
6
8
10
12
14
Death MI TVR Death/MI
% o
f ev
ent
Ontario Registry Clinical endpoints to 2 years in propensity matched
cohort
P=0.001 P=0.95
P<0.001
DES ( N=3751)
BMS (N=3751)
P=0.02
Tu et al. N Engl J Med 2007;357:1393-1402.
3.2
2.21.9
1.6
3.0
2.1
1.3
2.1
0
2
4
Death MI TVR Death/MI
% o
f ev
ent
Ontario Registry Clinical endpoints > 1 to 2 years in propensity
matched cohortDES ( N=3751)
BMS (N=3751)
P values not available
Tu et al N Engl J Med 2007;357:1393-1402.
Mauri AHA 2007
Mauri AHA 2007
Stefan James, Jörg Carlsson, Johan Stefan James, Jörg Carlsson, Johan Lindbäck, Tage Nilsson, Ulf Stenestrand, Lindbäck, Tage Nilsson, Ulf Stenestrand, Lars Wallentin and Bo Lagerqvist for the Lars Wallentin and Bo Lagerqvist for the
SCAAR study groupSCAAR study groupNone of the authors have any conflicts of interest in relation to the
presentation
Long term outcome with drug eluting stents vs
bare metal stents in Sweden – one additional year of follow-up
RestenosisRestenosisone stent cohortone stent cohort
0 1 2 3 40
.00
0.0
20
.04
0.0
60
.08
0.1
0
2004-2005, Adjusted
Time (years)
Cu
mu
lativ
e r
isk
of r
est
en
osi
s
BMSDES
BMS 8235 7708 7505 6326 4602 2668 753 0 0DES 5438 5223 5097 3809 2294 1110 257 0 0
RR: 0.48 (0.39, 0.58)
0 1 2 3 4
0.0
00
.02
0.0
40
.06
0.0
80
.10
2004-2005, Crude
Time (years)
Cu
mu
lativ
e r
isk
of r
est
en
osi
s
BMSDES
BMS 9217 8615 8399 7147 5205 3057 887 0 0DES 6229 5967 5822 4429 2738 1334 317 0 0
Unadjusted Adjusted
James ESC 2007
0 1 2 3 4
0.0
00
.05
0.1
00
.15
0.2
00
.25
2003-2005, Adjusted
Time (years)
Cu
mu
lativ
e r
isk
of d
ea
th o
r M
I
BMSDES
BMS 18769 17326 16957 14414 11596 8755 5523 2934 7DES 12015 11286 11003 7648 4956 3062 1498 535 0
RR: 1.01 (0.94, 1.09)
Adjusted death /MIAdjusted death /MI
0 1 2 3 4
0.0
00
.05
0.1
00
.15
0.2
00
.25
2003-2005, Adjusted
Time (years)
Cu
mu
lativ
e r
isk
of d
ea
th o
r M
I
BMSDES
BMS 12556 11701 11453 9731 7799 5878 3739 1977 7DES 6381 6017 5875 4103 2644 1631 798 295 0
RR: 0.91 (0.82, 1.01)
Total cohort
N = 35 262
One stent cohort
N = 18 937
James ESC 2007
Death/MI-total cohort
Year by year
0 1 2 3 4
0.0
00
.05
0.1
00
.15
0.2
00
.25
2003 landmark
Time (years)
Cu
mu
lativ
e r
isk
of d
ea
th o
r M
I
BMSDES
BMS 6448 6037 5918 5820 5713 5612 5520 2934 7DES 1799 1685 1644 1607 1568 1539 1496 535 0
RR: 1.06 (0.86, 1.32)
RR: 1.31 (1.12, 1.53)
2003
0 1 2 3 4
0.0
00
.05
0.1
00
.15
0.2
00
.25
2004 landmark
Time (years)
Cu
mu
lativ
e r
isk
of d
ea
th o
r M
I
BMSDES
BMS 6737 6228 6090 5983 5883 3143 3 0 0DES 3880 3638 3550 3468 3388 1523 2 0 0
RR: 0.98 (0.83, 1.17)
RR: 1.22 (1.05, 1.43)
2004
0 1 2 3 4
0.0
00
.05
0.1
00
.15
0.2
00
.25
2005 landmark
Time (years)
Cu
mu
lativ
e r
isk
of d
ea
th o
r M
I
BMSDES
BMS 5584 5061 4949 2611 0 0 0 0 0DES 6336 5963 5809 2573 0 0 0 0 0
RR: 0.69 (0.59, 0.81)
RR: 0.93 (0.76, 1.13)
2005
James ESC 2007
Stent thrombosisStent thrombosis
Time (years)210
Cu
mu
lati
ve r
isk
of
sten
t th
rom
bo
sis
% 2
1
0
DES n=21 717BMS n=20 058
Stent type Total cohort
N = 41 775 stents
0.5% per year
Unadjusted
James ESC 2007
P < 0.001
All
cau
se m
ort
alit
y ra
te (
%) P = 0.052
P = NR
P < 0.001
P < 0.0001
P < 0.001 P = 0.004
N =
31
60
N =
40
61
N =
48
3
N =
87
1
N =
57
19
N =
53
99
N =
63
84
N =
78
34
N =
37
51
N =
37
51
N =
59
96
N =
13
59
N =
35
48
N =
88
47
BMS
DES
3-year 3-year 2-year 2-year 3-year 2-year 2-year
DES vs BMS registries at TCT 07DES vs BMS registries at TCT 07
SJ Park Harjai Vagonescu Hannan Ko B Brodie Jensen
DES vs. BMSDES vs. BMSConclusionsConclusions
Over 35,000 patients with DES, 2-4 year follow-Over 35,000 patients with DES, 2-4 year follow-up with adjustment for differences in back up with adjustment for differences in back ground characteristics:ground characteristics:
– No overall increase in mortality or risk of MI with DES No overall increase in mortality or risk of MI with DES use.use.
Reduced mortality in some of the registriesReduced mortality in some of the registries
– Sustained reduction in risk of TVR.Sustained reduction in risk of TVR.
– Slightly increased risk of ST and MI after initial 6 Slightly increased risk of ST and MI after initial 6 months, compensated by reduction of events in the months, compensated by reduction of events in the first 6 months.first 6 months.
New DES ResultsNew DES ResultsEverolimus-Eluting Everolimus-Eluting
XIENCE™ V chromium XIENCE™ V chromium cobalt stent. cobalt stent.
The SPIRIT of XIENCE™The SPIRIT of XIENCE™The SPIRIT Family of TrialsThe SPIRIT Family of Trials
Post-Post-CE Mark CE Mark ApprovalApproval
InternationalInternationalN = 2,000N = 2,000
Women onlyWomen only
SPIRIT SPIRIT WOMENWOMEN
Post-Post-CE Mark CE Mark ApprovalApproval
InternationalInternationalN = 3,000N = 3,000
Diabetic study Diabetic study N = 300 N = 300 RegistryRegistryN = 2,700N = 2,700
SPIRIT SPIRIT VV
US Peri US Peri ApprovalApproval
USUSN = 3,690N = 3,690
SPIRIT SPIRIT IVIV
Safety & Safety & PerformancePerformance
EuropeEuropeN = 60N = 60
SPIRIT SPIRIT FIRSTFIRST
Clinical Clinical Support for Support for CE LaunchCE Launch
InternationalInternationalN = 300N = 300
SPIRIT SPIRIT IIII
US & Japan US & Japan ApprovalApproval
US/ JapanUS/ JapanN = 1,380N = 1,380
(1,292/88)(1,292/88)
SPIRIT SPIRIT IIIIII
22::11
Up to two de Up to two de novo lesions, novo lesions,
maximum of one maximum of one lesion per lesion per
epicardial vesselepicardial vessel
Main US RCTMain US RCT2.5 – 3.75 mm*2.5 – 3.75 mm*
LL ≤ 28 mmLL ≤ 28 mmN N = 1,002= 1,002
XIENCE™ VXIENCE™ VN = 669N = 669
TAXUS® Control TAXUS® Control N = 333N = 333
• PI: Gregg Stone, MDPI: Gregg Stone, MD• RCT: Prospective, single blindRCT: Prospective, single blind• Primary end point: In-segment Late Loss at 8MPrimary end point: In-segment Late Loss at 8M• Stent Size: 2.5 – 3.5mm mm; Stent lengths: 8, 18, 28 mmStent Size: 2.5 – 3.5mm mm; Stent lengths: 8, 18, 28 mm• Angiographic and IVUS Follow-Up on 564 and 240 pts, respectively Angiographic and IVUS Follow-Up on 564 and 240 pts, respectively • Clinical follow-up at 30, 180, 270d and 1, 2, 3, 4 and 5 yearsClinical follow-up at 30, 180, 270d and 1, 2, 3, 4 and 5 years• 6 Months clopidogrel for all arms6 Months clopidogrel for all arms
SPIRIT IIISPIRIT III
SPIRIT III RCT DesignSPIRIT III RCT Design
Baseline DemographicsBaseline Demographics
XIENCE™ VXIENCE™ V 669 pts669 pts
TAXUSTAXUS®® 333 pts333 pts P-valueP-value
Age (in years)Age (in years) 63.2 63.2 ± ± 10.510.5 62.8 62.8 ± ± 10.210.2 0.540.54
Male (%)Male (%) 70.170.1 65.765.7 0.170.17
Hypertension Hypertension (%)(%) 76.276.2 74.074.0 0.480.48
Hypercholesterolemia Hypercholesterolemia (%)(%) 74.274.2 71.571.5 0.360.36
Diabetes mellitus (%)Diabetes mellitus (%) 29.629.6 27.927.9 0.600.60
Insulin requiring (%)Insulin requiring (%) 7.87.8 5.55.5 0.190.19
Current smoker Current smoker (%)(%) 23.423.4 22.522.5 0.810.81
Prior MI (%)Prior MI (%) 19.919.9 18.018.0 0.490.49
Unstable angina (%)Unstable angina (%) 18.718.7 25.125.1 0.020.02
SOURCE: G.W. Stone, ACC 2007.SOURCE: G.W. Stone, ACC 2007.
Baseline AngiographyBaseline AngiographyXIENCE™ VXIENCE™ V 767 lesions 767 lesions
TAXUSTAXUS®® 382 lesions382 lesions P-valueP-value
Lesion location Lesion location
LADLAD 41.3%41.3% 42.9%42.9% 0.610.61
LCXLCX 27.6%27.6% 28.3%28.3% 0.830.83
RCARCA 31.0%31.0% 28.5%28.5% 0.410.41
LMCALMCA 0.1%0.1% 0.3%0.3% 0.550.55
QCAQCA
RVD (mm)RVD (mm) 2.77 ± 0.452.77 ± 0.45 2.76 ± 0.462.76 ± 0.46 0.870.87
MLD (mm)MLD (mm) 0.82 ± 0.410.82 ± 0.41 0.83 ± 0.400.83 ± 0.40 0.790.79
% DS% DS 70.0 ± 13.370.0 ± 13.3 69.4 ± 13.669.4 ± 13.6 0.540.54
Lesion length (mm)Lesion length (mm) 14.7 ± 5.614.7 ± 5.6 14.7 ± 5.714.7 ± 5.7 0.920.92
SOURCE: G.W. Stone, ACC 2007.SOURCE: G.W. Stone, ACC 2007.
QCA at 8 Months (All Lesions)QCA at 8 Months (All Lesions)XIENCE™ VXIENCE™ V 344 lesions 344 lesions
TAXUSTAXUS®® 158 lesions158 lesions P-valueP-value
RVD (mm)RVD (mm) 2.77 ± 0.432.77 ± 0.43 2.78 ± 0.422.78 ± 0.42 0.840.84
MLD (mm)MLD (mm)
In-segmentIn-segment 2.22 ± 0.532.22 ± 0.53 2.12 ± 0.602.12 ± 0.60 0.080.08
In-stentIn-stent 2.56 ± 0.532.56 ± 0.53 2.45 ± 0.652.45 ± 0.65 0.070.07
Late Loss (mm)Late Loss (mm)
In-segmentIn-segment 0.14 ± 0.390.14 ± 0.39 0.26 ± 0.460.26 ± 0.46 0.0030.003
In-stentIn-stent 0.16 ± 0.410.16 ± 0.41 0.30 ± 0.530.30 ± 0.53 0.0020.002
Diameter Stenosis (%)Diameter Stenosis (%)
In-segmentIn-segment 18.8 ± 14.418.8 ± 14.4 22.8 ± 16.422.8 ± 16.4 0.0080.008
In-stentIn-stent 5.9 ± 16.45.9 ± 16.4 10.3 ± 21.410.3 ± 21.4 0.020.02
Binary Restenosis (%)Binary Restenosis (%)
In-segmentIn-segment 4.74.7 8.98.9 0.070.07
In-stentIn-stent 2.32.3 5.75.7 0.060.06SOURCE: G.W. Stone, ACC 2007.
SPIRIT III Clinical Results SPIRIT III Clinical Results
0.5% 0.5%
2.0%2.6%
4.6%
0.0%0.6%
2.5%
5.0%
8.1%
0%
2%
4%
6%
8%
10%
StentThrombosis
CardiacDeath
MI TLR MACE
XIENCE V TAXUS®N = 658N = 658 N = 322N = 322
P = 0.55P = 0.55 P = 0.67P = 0.67 P = 0.64P = 0.64 P = 0.053P = 0.05344% Reduction44% Reduction
P = 0.028P = 0.028
G.W. Stone, ACC 2007.G.W. Stone, ACC 2007.
Meta-Analysis of Meta-Analysis of Patient Level Data Patient Level Data N = 1,302N = 1,302
SPIRIT II & III Pooled Meta-SPIRIT II & III Pooled Meta-AnalysisAnalysis
Similar inclusion and Similar inclusion and exclusion criteria: Up exclusion criteria: Up
to two de novo to two de novo lesions, maximum of lesions, maximum of
one lesion per one lesion per epicardial vessel epicardial vessel
2.5 – 3.75 mm*2.5 – 3.75 mm*LL ≤ 28 mmLL ≤ 28 mm
XIENCE™ VXIENCE™ VN = 892N = 892
TAXUS® Control TAXUS® Control N = 410N = 410
SPIRIT II + IIISPIRIT II + III
• Presented by Gregg Stone, MD at PCR, 5/22/07Presented by Gregg Stone, MD at PCR, 5/22/07• Independent Meta-Analysis done by CRFIndependent Meta-Analysis done by CRF• SPIRIT II and SPIRIT III have similar inclusion and SPIRIT II and SPIRIT III have similar inclusion and
exclusion criteriaexclusion criteria• Pooled, patient level analysis of combined SPIRIT II and Pooled, patient level analysis of combined SPIRIT II and
SPIRIT III dataSPIRIT III data• Pre-specified, Superiority Testing on all endpointsPre-specified, Superiority Testing on all endpoints
*SPIRIT II was up to 4.0mm
SPIRIT II & III Meta-AnalysisSPIRIT II & III Meta-Analysis
0.14
0.11
0.33
0.22
0.00
0.10
0.20
0.30
0.40
In-stent In-segment
XIENCE V TAXUS®
Late LossLate Loss Binary RestenosisBinary Restenosis
mm
mm
1.9%
4.1%
4.9%
7.8%
0%
2%
4%
6%
8%
10%
In-stent In-segment
58% Reduction58% ReductionP < 0.0001P < 0.0001
50% Reduction50% ReductionP = 0.0004P = 0.0004
61% Reduction61% ReductionP = 0.02P = 0.02
47% Reduction47% ReductionP = 0.039P = 0.039
N = 581N = 581 N = 244N = 244SOURCE: G.W. Stone, PCR 2007.SOURCE: G.W. Stone, PCR 2007.NOTE: This analysis was performed by the SPIRIT III investigator and is meant for descriptive purposes only. Please note that the data were NOTE: This analysis was performed by the SPIRIT III investigator and is meant for descriptive purposes only. Please note that the data were from different patient populations (OUS vs. US) and had different angiographic follow-up time points (6 months vs. 8 months). from different patient populations (OUS vs. US) and had different angiographic follow-up time points (6 months vs. 8 months).
SPIRIT II & III Meta-AnalysisSPIRIT II & III Meta-Analysis
0.5%
1.7%
0.4%
2.1%
0.9%
2.4%
0.3%
2.7%
0.8%
3.2%
1.0%
3.5%
0%
1%
2%
3%
4%
5%
StentThrombosis
MI CardiacDeath
CardiacDeath or MI
All Death All Death orMI
XIENCE V TAXUS®N = 878N = 878 N = 398N = 398
9M E
ven
t R
ate
9M E
ven
t R
ate
P = 0.59P = 0.59 P = 0.22P = 0.22 P = 0.32P = 0.32 P = 0.19P = 0.19 P = 0.87P = 0.87 P = 0.31P = 0.31
Safety EndpointsSafety Endpoints
SOURCE: G.W. Stone, PCR 2007.SOURCE: G.W. Stone, PCR 2007.
Number at riskNumber at riskXIENCE™ VXIENCE™ V 892892 879879 867867 793793TAXUSTAXUS 408408 397397 389389 349349
Isch
emic
TL
R (
%)
Isch
emic
TL
R (
%)
Time in months
HR [95% CI]0.47 [0.26,0.87]
p=0.01
XIENCE VXIENCE V TAXUSTAXUS
5.1%
2.4%
9630
8
10
6
4
2
0
SPIRIT II & III TLRSPIRIT II & III TLR
SOURCE: G.W. Stone, PCR 2007.SOURCE: G.W. Stone, PCR 2007.
Number at riskNumber at riskXIENCE™ VXIENCE™ V 888888 871871 858858 783783TAXUSTAXUS 407407 388388 380380 341341
Isch
emic
MA
CE
(%
)Is
chem
ic M
AC
E (
%)
Time in monthsTime in months
HR [95% CI]0.50 [0.31,0.81]
p=0.004
XIENCE VXIENCE V TAXUSTAXUS
8.0%
4.1%
9630
8
10
6
4
2
0
SPIRIT II & III MACESPIRIT II & III MACE
SOURCE: G.W. Stone, PCR 2007.SOURCE: G.W. Stone, PCR 2007.
SPIRIT III Conclusions ISPIRIT III Conclusions I In the large, multicenter, randomized SPIRIT III trial, In the large, multicenter, randomized SPIRIT III trial,
the Everolimus-Eluting XIENCE™ V stent compared to the Everolimus-Eluting XIENCE™ V stent compared to
the Paclitaxel-Eluting TAXUSthe Paclitaxel-Eluting TAXUS® ® stent:stent:
– Was both non-inferior and superior in reducing in-Was both non-inferior and superior in reducing in-
segment late loss, the primary endpoint of the trialsegment late loss, the primary endpoint of the trial
– Significantly reduced in-stent late loss at 8 monthsSignificantly reduced in-stent late loss at 8 months
– Reduced angiographic FU diameter stenosis with a Reduced angiographic FU diameter stenosis with a
strong trend toward lower binary restenosisstrong trend toward lower binary restenosis
– Resulted in a significant reduction in in-stent volume Resulted in a significant reduction in in-stent volume
obstruction without excess late acquired malappositionobstruction without excess late acquired malapposition
SPIRIT III Conclusions IISPIRIT III Conclusions II In the large, multicenter, randomized SPIRIT III trial, the In the large, multicenter, randomized SPIRIT III trial, the
Everolimus-Eluting XIENCE™ V stent compared to the Everolimus-Eluting XIENCE™ V stent compared to the
Paclitaxel-Eluting TAXUSPaclitaxel-Eluting TAXUS®® stent: stent:
Demonstrated non-inferior rates of TVF at 9-months, with a Demonstrated non-inferior rates of TVF at 9-months, with a
significant 44% reduction in MACEsignificant 44% reduction in MACE
Showed a strong trend toward reduced ischemia-driven TLR, with a Showed a strong trend toward reduced ischemia-driven TLR, with a
significant reduction in any TLRsignificant reduction in any TLR
Had similar rates of death, MI and stent thrombosisHad similar rates of death, MI and stent thrombosis
The primary and major secondary endpoints of the SPIRIT III The primary and major secondary endpoints of the SPIRIT III
trial were mettrial were met
BivalirudinBivalirudin
Rationale for Use: Pharmacologic Intervention in Rationale for Use: Pharmacologic Intervention in ThrombosisThrombosis
UFH=unfractionated heparin.LMWH=low-molecular-weight heparinADP=adenosine diphosphate.TFPI=tissue factor pathway inhibitor
Selwyn A. Am J Cardiol. 2003;91:3H-11H.
Coagulation cascade Platelets
LMWH
Thienopyridines
GP IIb/IIIa inhibitors
Thrombolytics
LMWHUFH
LMWHUFH
Direct thrombininhibitors
Tissue factor
Factor Xa
Prothrombin
Thrombin
Platelets
A2 vWF ADP
Activated platelets
Fibrinogen cross-linking
Platelet aggregation
Aspirin
Fibrinogen Fibrin Fibrindegradation
Collagen Leukocytes
TFPI
Anti-thrombin
Anti-thrombin
Thromboxane
PlasminThrombus
Conclusion HORIZONS AMIConclusion HORIZONS AMI
Bivalirudin used during acute STEMI PCI Bivalirudin used during acute STEMI PCI as mono-therapy when compared to as mono-therapy when compared to heparin + IIb/IIIa, heparin + IIb/IIIa, Reduced bleeding complication.Reduced bleeding complication.Similar MACESimilar MACEReduce cardiac death. Reduce cardiac death.
COURAGE: COURAGE: CClinicallinical OOutcomesutcomes UUtilizingtilizing RRevascularizationevascularization and and AAggressive ggressive
GGuideline-Drivenuideline-Driven Drug Drug EEvaluationvaluation
Boden W et al. NEJM. 2007;356:1503-1516.
CharacteristicPCI + OMT (N=1149)
OMT (N=1138) P Value
Age – yr. 62 ± 10.1 62 ± 9.7 0.54
Sex % 0.95
Male 85 % 85 %
Female 15 % 15 %
Race or Ethnic group % 0.64
White 86 % 86 %
Non-white 14 % 14 %
CLINICAL
Angina (CCS – class) % 0.24
0 and I 42 % 43 %
II and III 59 % 56 %
Median angina duration 5 (1-15) months 5 (1-15) months
Median angina episodes/week 3 (1-6) 3 (1-6)
Baseline Clinical andBaseline Clinical andAngiographic CharacteristicsAngiographic Characteristics
42 % 43 %
3 (1-6) 3 (1-6)
Boden W et al. NEJM. 2007;356:1503-1516.
CharacteristicPCI + OMT (N=1149)
OMT (N=1138) P Value
CLINICAL
Stress test 0.84 Total patients – % 85 % 86 % Treadmill test 57 % 57 % 0.84 Pharmacologic stress 43 % 43 %Nuclear imaging – % 70 % 72 % 0.59 Single reversible defect 22 % 23 % 0.09 Multiple reversible defects 65 % 68 % 0.09ANGIOGRAPHIC Vessels with disease – % 0.72 1, 2, 3 31, 39, 30 % 30, 39, 31 % Disease in graft 62 % 69 % 0.36 Proximal LAD disease 31 % 37 % 0.01 Ejection fraction 60.8 ± 11.2 60.9 ± 10.3 0.86
Baseline Clinical andBaseline Clinical andAngiographic CharacteristicsAngiographic Characteristics
70% Multi-vessel Disease
70% Multi-vessel Disease
70% Multi-vessel Disease
70% Multi-vessel Disease
Boden W et al. NEJM. 2007;356:1503-1516.
PCI OutcomesPCI Outcomes1149 patients total1149 patients total
46 (4%) procedure not attempted46 (4%) procedure not attempted27 (2%) no lesions crossed27 (2%) no lesions crossed
1077 patients (94%) had PCI attempted1077 patients (94%) had PCI attempted
1577/1688 lesions had PCI success (93%)1577/1688 lesions had PCI success (93%)
787 patients (69%) had 2 or 3 vessel ds.787 patients (69%) had 2 or 3 vessel ds.590 pts (59%) received 1 stent590 pts (59%) received 1 stent
416 pts (41%) received ≥2 stents416 pts (41%) received ≥2 stentsAt least 371 of 787 pts (47%) with multivessel At least 371 of 787 pts (47%) with multivessel
disease had incomplete revascularization disease had incomplete revascularization
Boden WE et al. Boden WE et al. NEJMNEJM. 2007;356:1503-1516.. 2007;356:1503-1516.
97% BMS97% BMS3% DES3% DES
COURAGE COURAGE "Hard Outcomes""Hard Outcomes"
7.69.3
21.6
31.6
10.48.3
0
5
10
15
20
25
30
35
% o
f P
atie
nts
PCIPCI OMTOMT PCIPCI OMTOMT PCIPCI OMTOMT
DeathDeath Spontaneous MISpontaneous MI RevascularizationRevascularization
9%11%
33%
with DES
Moses, J. Data Analysis. April 2007
COURAGE Nuclear Sub-study II
Leslee J. Shaw, Daniel S. Berman, David J. Maron, G. B. John Mancini, Sean W. Hayes, Pamela M. Hartigan, William S. Weintraub, Robert A. O’Rourke, Marcin
Dada, John A. Spertus, Bernard R. Chaitman, John Friedman, Piotr Slomka, Gary V. Heller, Guido Germano, Gilbert Gosselin, Peter Berger, William J. Kostuk,
Ronald Schwartz, Merill Knudtson, Emir Veledar, Eric R. Bates, Benjamin McCallister, Koon K. Teo, William E. Boden for the COURAGE Investigators
Nuclear substudy (n=314 /
2287)
Shaw et al. J Nucl Cardiol 2006;13:685-98.
Documented pre-Rx ischemia
PCI + OMT(n=159)
OMT (n=155)
Repeat MPS*at 6-18m
Repeat MPS*at 6-18m
Hypothesis: reduction in ischemia will be greater for patients randomized to PCI+OMT than for those randomized to OMT
Serial rest/stress myocardial perfusion SPECT (MPS)
*timing chosen to occur beyond window of in-stent restenosis & delayed to allow effects of medical Rx to be observed
• pre-Rx = off meds
to compare patient management strategy for ischemia reduction
• 6-18m = on meds
Mean = 374 ±50 days
% ischemic myocardium:% ischemic myocardium: (stress TPD-rest TPD)(stress TPD-rest TPD) < 5%: minimal (“no ischemia”)< 5%: minimal (“no ischemia”) 5.0%-9.9%: mild5.0%-9.9%: mild 10%: moderate-to-severe10%: moderate-to-severe
Significant reduction in ischemia:Significant reduction in ischemia: 5% reduction in ischemic myocardium*5% reduction in ischemic myocardium*
MPS ischemia based onMPS ischemia based ontotal perfusion deficit (TPD)total perfusion deficit (TPD)
Slomka et al. J Nucl Cardiol 2005;12:66-77
Defect extent
TPD Lower NllimitLower Nllimit
DefectseverityDefectseverity
TPD: quantitative measure of defect extent & severity
*threshold exceeds test repeatability*threshold exceeds test repeatability
OMT (n=155)PCI + OMT (n=159)PCI + OMT (n=159)
Mean = -2.7% (95% CI = -3.8% to -1.7%)
8.6% 8.1%
(6.9%-9.4%)
8.2% 5.5%
(4.7%-6.3%)
MPS % ischemic myocardium (95% CI) pre-Rx & 6-18m
Mean = -0.5% (95% CI = -1.6% to 0.6%)
p<0.0001
Primary endpoint: % with ischemia Primary endpoint: % with ischemia reduction ≥ 5% myocardium reduction ≥ 5% myocardium
(N=314)(N=314)
19.8% p=0.004
33.3%
Isch
emia
redu
ctio
n ≥
5%
52.0% p=0.007
78.0%
Isch
emia
redu
ctio
n ≥
5%
% with ischemia reduction ≥5% myocardium
(n=105 moderate-to-severe pre-Rx ischemia)
RR=0.47 (95% CI=0.23-0.95)
p=0.037
Rates of death or MI by ischemia reductionRates of death or MI by ischemia reductionD
eath
or M
I rat
e (%
)
24.7%
13.4%
(n=82) (n=232)
pp=0.001=0.001
Rates of death or MI by ischemia reduction in subset of 105 patients with
moderate-to-severe pre-Rx ischemia
(n=68) (n=37)
32.4%
16.2%
Dea
th o
r MI r
ate
(%)
Rates of death or MI by residual Rates of death or MI by residual ischemia on 6-18m MPSischemia on 6-18m MPS
p=0.063
p=0.023
p=0.002
(n=23) (n=88)(n=141) (n=62)
22.3%
0.0%
39.3%
15.6%
Dea
th o
r MI r
ate
(%)
Conclusions Conclusions
PCI added to OMT was more effective in reducing ischemia and improving angina than OMT, particularly in patients with moderate-to-severe pre-Rx ischemia
Randomized trials of management strategies should evaluate quantitative measures of myocardial perfusion ischemia to guide clinical decisions regarding revascularization during long-term management
Drug Eluting BalloonDrug Eluting Balloon
Scheller Heart 2007, 93: 539-41
DES vs. DEB (PACCOCATH)DES vs. DEB (PACCOCATH)
Hwang, Circulation 2001; 104: 600-5
Instant and short term drug release from balloon
~ 300 - 600 µg PaclitaxelNo polymeresNo permanent mechanical irritation
Stenting optional
Slow and continuous drug release from stent struts
~100 - 200 µg Paclitaxel / Sirolimus
Polymeres with associated reactions
Implies stent deployment
DES
DEB
The The PPaclitaxel-aclitaxel-EEluting luting PPTCA-Balloon TCA-Balloon Catheter in Catheter in CCoronary oronary AArtery rtery DDiseaseisease
PEPCAD I-SVDPEPCAD I-SVD
PEPCAD II-ISRPEPCAD II-ISR
Outcome ComparisonDEB ITTDEB ITT
N=120N=120
DEB OnlyDEB Only
N=82N=82
Taxus*Taxus* BMS*BMS*
Follow-up Follow-up [mo][mo]
6.4±1.36.4±1.3 6.4±1.26.4±1.2 99 99
Late loss Late loss [mm][mm]
0.32±0.560.32±0.56 0.18±0.380.18±0.38 0.490.490.610.61 0.900.900.630.63
Restenosis Restenosis (segment)(segment)
15.5%15.5% 5.5%5.5% 31.2%31.2% 49.4%49.4%
Total MACETotal MACE 15%15% 6.1%6.1% 18.9%18.9% 26.9%26.9%
TLRTLR 11.7%11.7% 4.9%4.9% 10.4%10.4% 21.5%21.5%
Myocardial Myocardial infarctioninfarction
1.7%1.7% 1.2%1.2% 5.7%5.7% 2.2%2.2%
Cardiac deathCardiac death 0%0% 0%0% 1.9%1.9% 1.1%1.1%
*Stone, G JAMA 2005;294:1215-23
Summary PEPCAD I Summary PEPCAD I
The paclitaxel-eluting balloon catheter The paclitaxel-eluting balloon catheter Sequent PleaseSequent Please (B.Braun Melsungen AG) (B.Braun Melsungen AG) … … –was safe and associated with a high was safe and associated with a high procedural success rate in de-novo lesions procedural success rate in de-novo lesions
–exhibited low late lumen loss after 6 months in exhibited low late lumen loss after 6 months in SVDSVD
–patients treated w/o additional stenting patients treated w/o additional stenting demonstrated a demonstrated a restenosis rate of 5.5%restenosis rate of 5.5%
The The PPaclitaxel-aclitaxel-EEluting luting PPTCA-TCA-Balloon Catheter in Balloon Catheter in CCoronary oronary
AArtery rtery DDiseaseisease
PEPCAD I-SVDPEPCAD I-SVD
PEPCAD II-ISRPEPCAD II-ISR
The The PPaclitaxel-aclitaxel-EEluting luting PPTCA-TCA-Balloon Catheter in Balloon Catheter in CCoronary oronary
AArtery rtery DDiseaseisease
PEPCAD I-SVDPEPCAD I-SVD
PEPCAD II-ISRPEPCAD II-ISR
Event Free Survival (ITT/AsT)Event Free Survival (ITT/AsT)
70
75
80
85
90
95
100
0 2 4 6 8 10
Sub
ject
s [%
]
DES/ I TT DEB/ I TT
DES/AsT DEB/AsT
p=0.07
p=0.007
Months post PCI
Outcome (AsT: N=126)DEB (N=66)DEB (N=66) DES (N=60)DES (N=60) P=P=
Follow-up:clinical[months]Follow-up:clinical[months] 6.2 ± 0.86.2 ± 0.8 6.2 ± 0.86.2 ± 0.8 0.70.7
Follow-up: clinical [N]Follow-up: clinical [N] 64 (97.0%)64 (97.0%) 60 (100%)60 (100%) 0.40.4
Follow-up: angiographicFollow-up: angiographic 58 (87.9%)58 (87.9%) 54 (90.0%)54 (90.0%) 0.80.8
Late lumen loss [mm]Late lumen loss [mm] 0.19 ± 0.380.19 ± 0.38 0.47 ± 0.710.47 ± 0.71 0.030.03
Binary restenosis insegmentBinary restenosis insegment 2/58 2/58 (3.4%)(3.4%) 11/54 11/54 (20.4%)(20.4%) 0.0070.007
TLRTLR 2/64 (3.1%)2/64 (3.1%) 10/60 (16.7%)10/60 (16.7%) 0.020.02
Myocardial infarctionMyocardial infarction 0/64 (0.0%)0/64 (0.0%) ff1/60 (1.7%)1/60 (1.7%) 11
DeathDeath *2/64 (3.1%)*2/64 (3.1%) **1/60 (1.7%)**1/60 (1.7%) 11
Total MACE Total MACE (w/o noncardiac death)(w/o noncardiac death) 3/64 (4.7%)3/64 (4.7%) 11/60 (18.3%)11/60 (18.3%) 0.020.02
fNSTEMI due to side branch occlusion
*1 cardiac, not lesion related 2 non cardiac** non-cardiac death
The PEPCAD ProgramThe PEPCAD ProgramPaclitaxel-Eluting PTCA-Catheter in Coronary Artery DiseasePaclitaxel-Eluting PTCA-Catheter in Coronary Artery Disease
TitleTitle DesignDesign StatusStatus PIPI
PEPCAD I SVDPEPCAD I SVD Sequent in Sequent in ≤2.8mm, ≤2.8mm, 120px, multi-center, GER120px, multi-center, GER
6mo-FU 6mo-FU MU, CRIMU, CRI
PEPCAD II ISRPEPCAD II ISR Sequent vs Taxus in ISRSequent vs Taxus in ISR, , 131px, multi-center, GER131px, multi-center, GER
6mo-FU 6mo-FU MU, CRIMU, CRI
PEPCAD III PEPCAD III Sequent + pre-loaded Sequent + pre-loaded Coroflex Blue vs Cypher, Coroflex Blue vs Cypher, 600 px, Europe600 px, Europe
Q2/07 Q2/07 activeactive
B.SchellerB.Scheller
PEPCAD IV DMPEPCAD IV DM Sequent vs Taxus in DMSequent vs Taxus in DM, , 160px, multi-center, 160px, multi-center, Thailand, Malaysia Thailand, Malaysia
Q2/07 Q2/07 activeactive
D.Rosli, D.Rosli, MU, CRIMU, CRI
PEPCAD V BIFPEPCAD V BIF Sequent, 25px, dual-Sequent, 25px, dual-center, GERcenter, GER
Q3/ 07 Q3/ 07 activeactive
D.Mathey D.Mathey MU, MU, CRICRI
INDICORINDICOR Coroflex Blue+Sequent,Coroflex Blue+Sequent, Real World, 100pxReal World, 100px
PlanningPlanning U.Kaul, U.Kaul, MU, CRIMU, CRI
2007, The year in PCI2007, The year in PCIConclusionsConclusions
DESDES– Multiple registries of real world DES usage showing that as compared to BMSMultiple registries of real world DES usage showing that as compared to BMS
DES improve outcome, and do so safely. Reduced mortality in some registriesDES improve outcome, and do so safely. Reduced mortality in some registries Sustained reduction in TVR.Sustained reduction in TVR. Slight increase in ST beyond 6 months compensated by reduction in TVR.Slight increase in ST beyond 6 months compensated by reduction in TVR.
– New DES, New DES, Everolimus-Eluting XIENCE™ V stentEverolimus-Eluting XIENCE™ V stent Similar rates of ST, MI and deathSimilar rates of ST, MI and death Favorable reduction in late loss and TVR.Favorable reduction in late loss and TVR.
BivalirudinBivalirudin– When used during acute STEMI PCI as mono-therapy as compared to heparin + When used during acute STEMI PCI as mono-therapy as compared to heparin +
IIb/IIIa, IIb/IIIa, Reduced bleeding complication.Reduced bleeding complication. Similar MACESimilar MACE Reduce cardiac death. Reduce cardiac death.
PCI in stable CADPCI in stable CAD– Courage trial, PCI with BMS for stable CAD vs. aggressive medical rx. onlyCourage trial, PCI with BMS for stable CAD vs. aggressive medical rx. only
Similar mortalitySimilar mortality Similar outcome for composite death, MI, CVA, hospitalization for ACS.Similar outcome for composite death, MI, CVA, hospitalization for ACS. Reduced symptoms with decreased need for future revascularization.Reduced symptoms with decreased need for future revascularization. Nuclear sub study showed that patients with moderate to severe ischemia had nearly Nuclear sub study showed that patients with moderate to severe ischemia had nearly
50% reduction in death and MI.50% reduction in death and MI. Residual ischemia is a predictor of increased mortality.Residual ischemia is a predictor of increased mortality.
2007, The year in PCI2007, The year in PCIConclusionsConclusions
Acute MI PCIAcute MI PCI– Use of thrombus aspiration catheter prior to stentingUse of thrombus aspiration catheter prior to stenting
Improved myocardial blush gradeImproved myocardial blush grade Improved ST resolution and reduced persistent ST deviationImproved ST resolution and reduced persistent ST deviation With improved myocardial perfusion, reduced mortality and MACE.With improved myocardial perfusion, reduced mortality and MACE.
New Technology, DEBNew Technology, DEB– Paclitaxel eluting DEBPaclitaxel eluting DEB
was safe and associated with a high procedural success rate in ISR was safe and associated with a high procedural success rate in ISR exhibited low late lumen loss after 6 months in ISRexhibited low late lumen loss after 6 months in ISR was superior to the paclitaxel-eluting Taxuswas superior to the paclitaxel-eluting Taxus stent in ISR after 6 stent in ISR after 6
monthsmonths was not associated with late thrombosis in was not associated with late thrombosis in 250 patient years in 250 patient years in
ISRISR
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