Advances and Future in PCI v1 - summitmd.comsummitmd.com/pdf/pdf/3_Windecker.pdf ·...
Transcript of Advances and Future in PCI v1 - summitmd.comsummitmd.com/pdf/pdf/3_Windecker.pdf ·...
Angioplasty Summit, TCTAPS l A il 25th 2012Seoul, April 25th 2012
Advances and Future in PCI
Stephan WindeckerStephan Windecker
Department of CardiologyDepartment of Cardiology
Swiss Cardiovascular Center and Clinical Trials Unit Bern
Bern University Hospital, Switzerland
Scientific Advances and Cardiovascular MortalityCardiovascular Mortality
Nabel and Braunwald. N Engl J Med 2012;366:54‐631958
CoronaryCoronaryarteriographydeveloped(Sones)
2002Efficacy ofdrug‐elutingvs. bare‐
19771977Coronary
angioplasty
vs. baremetal stentsdetermined
developed(Grüntzig) 1993
Superiority ofprimary PCI vsprimary PCI vs. fibrinolysis in acute MI noted
MortalityMortality andand Repeat Repeat RevascularizationRevascularization withwithEarly Generation DES versus BareEarly Generation DES versus Bare MetalMetal StentsStentsEarly Generation DES versus Bare Early Generation DES versus Bare MetalMetal StentsStents
Mortality Repeat RevascStettler C et al. Lancet 2007;370:937‐48
Mortality Repeat Revasc
SES vs BMS 1 00 (0 82 1 25) SES vs BMS 0 30 (0 24 0 37)
HR (95% CI) HR (95% CI)
SES vs BMS
PES vs BMS
SES vs PES
1.00 (0.82‐1.25)
1.03 (0.84‐1.22)
0 96 (0 83 1 24)
SES vs BMS
PES vs BMS
SES vs PES
0.30 (0.24‐0.37)
0.42 (0.33‐0.53)
0 70 (0 56 0 84)
10∙2 2 50∙5
SES vs PES 0.96 (0.83‐1.24)
10∙2 2 50∙5
SES vs PES 0.70 (0.56‐0.84)
50
30
40
50NNT=35(CI 23-65)
10
20
30
NNT=7(CI 6 8)
NN
T
NNT=8(CI 7 10)
0
10
SES vs BMS PES vs BMS SES vs PES
(CI 6-8) (CI 7-10)
Progress Progress WithWith NewerNewer Generation DrugGeneration Drug‐‐ElutingEluting StentsStents
Newer Generation DES Efficacy and Safety
E liE li El tiEl ti Si liSi li El tiEl ti St tSt tEverolimusEverolimus--ElutingEluting versus versus SirolimusSirolimus--ElutingEluting StentsStents
Target Lesion Revasc Definite STTarget Lesion Revasc Definite ST
Favors EES Favors SES Favors EES Favors SES
Stefanini, WindeckerUpdated Meta-Analysis N = 11,167
BernBern‐‐Rotterdam Rotterdam CohortCohort Study Study Very Late Definite ST (1 4 yrs)
5EES vs SES HR* 0 33 95% CI 0 15 0 72
Very Late Definite ST (1-4 yrs)Räber et al. Circulation 2012; 125:1110-21
4
%)
EES vs. SES HR* = 0.33, 95% CI 0.15 – 0.72, P=0.006
EES vs. PES HR* = 0.24, 95% CI 0.13‐0.47,
3
cide
nce
(% P <0.0001
Paclitaxel Stent 2 4%
2
ulat
ive
inc Paclitaxel Stent 2.4%
1
Cum
u
Sirolimus Stent 1.6%
0 Everolimus Stent 0.6%
0 6 12 18 24 30 36 42 48Months after index PCI
*from Cox proportional hazards model
StentStent ThrombosisThrombosis WithWith EverolimusEverolimus‐‐ElutingElutingStentsStents andand BareBare MetalMetal StentsStentsStentsStents andand Bare Bare MetalMetal StentsStents
A Network Meta-AnalysisPalmerini T et al Lancet 2012Palmerini T et al. Lancet 2012
Impact of PolymerImpact of Polymer‐‐Drug Coating and Platform Drug Coating and Platform Design on Early StentDesign on Early Stent ThrombogenicityThrombogenicityDesign on Early Stent Design on Early Stent ThrombogenicityThrombogenicity
Kolandaivelu K et al. Circulation 2011;123:1400-1409.
P=0.011 P=0.036
n81
umSten
t/MLV
ision
G Adsorba
nceS
LD
Pooled BMS: ML Vision, Driver, Taxus, Bx VelocityPooled DES: Xience V, Endeavor, Taxus Libertè, Cypher
Biodegradable Polymer Based DES Platforms
Sirolimus – ISAR TEST Biolimus A9 – BioMatrixNobori, Axxess, XTENT Sirolimus – ORSIRO
Sirolimus – Genous E erolim s SYNERGY No olim s DES ne BDBioengineered R Stent Everolimus – SYNERGY Novolimus – DESyne BD
LEADERS Trial – Primary EndpointCardiac death MI or Clinically indicated TVRCardiac death, MI, or Clinically-indicated TVR
Stefanini G et al. Lancet 2011;378:1940-8
25
BES SES
23.1%
3-year RR0.80 (0.63 - 1.01)
2-year RR0.83 (0.64 - 1.07)
4-year RR0.81 (0.66 - 1.00)
1-year RR0.88 (0.66 - 1.17)
15
20
19.1%15.5%
19.3%
Δ 3.7
Δ 4.0
10
15
% 13%15.6%12.1%
Δ 1.4
Δ 2.5
P < 0 00015
10.7%Pnon-inferiority < 0.0001
Psuperiority = 0.050
00 6 12 18 24 30 36 42 48
MonthsN b t i kNumbers at risk
SES 850 775 738 718 702 676 656 639 614
BES 857 781 749 733 723 710 697 677 659
BiodegradableBiodegradable Polymer DES versus Polymer DES versus Durable PolymerDurable Polymer SirolimusSirolimus ElutingEluting StentsStentsDurable Polymer Durable Polymer SirolimusSirolimus ElutingEluting StentsStents
Stefanini G et al. Lancet 2011
DESDES SafetySafety –– RiskRisk ofof StentStent ThrombosisThrombosis
Definite ST Definite ST
DES DES SafetySafety –– RiskRisk ofof StentStent ThrombosisThrombosis
BP‐DES DP‐SES RR (95% CI)
in available randomized studies in LEADERS trial through 4 years fup
1 to 4 year* RR 0.20 (95% CI 0.06‐0.67)
p=0.004ISAR TEST 4
ISAR‐TEST 3
9/1299
1/202
9/652
2/202
0 50 (0 20 1 26)
0∙50 (0∙05, 5∙47) 0 to 1 year*RR 0.99 (95% CI 0.51‐1.95)
p=0.98
LEADERS
ISAR‐TEST 4
20/857
9/1299
32/850
9/652
0∙62 (0∙36, 1∙08)
0∙50 (0∙20, 1∙26)
Overall (I‐squared = 0∙0%, p=0∙92) 0∙58 (0∙37, 0∙93)
10∙1 0∙2 2 50∙5
* RR 0‐1 vs RR 1‐4 p for interaction=0.017
Favoursbiodegradablepolymer DES
Favoursdurable
polymer SES
Risk ratio
Biodegradable Polymer BES vs Durable Polymer SESAssociation of Cardiac Events With Definite ST
BES SES RR (95% CI) P P‐interNOT ASSOCIATED with ST
Association of Cardiac Events With Definite ST Stefanini G et al. Lancet 2011;378:1940-8
Cardiac death, MI, or TVR 0∙70≤1 year 78/857 87/850 0∙89 (0∙65‐1∙20) 0∙441 to 4 years 67/749 79/738 0∙81 (0∙59‐1∙12) 0∙21
Cardiac death or MI 0∙43
NOT ASSOCIATED with ST
Cardiac death or MI 0 43≤1 year 48/857 47/850 1∙02 (0∙68‐1∙53) 0∙941 to 4 years 43/779 52/781 0∙80 (0∙54‐1∙21) 0∙30
Clinically‐indicated TVR 0∙64≤1 year 37/857 45/850 0∙81 (0∙52‐1∙25) 0∙33≤1 year 37/857 45/850 0 81 (0 52 1 25) 0 331 to 4 years 39/776 40/760 0∙94 (0∙60‐1∙45) 0∙77
C di d th MI TVR 0 049
ASSOCIATED with STCardiac death, MI, or TVR 0∙049
≤1 year 13/857 15/850 0∙86 (0∙41‐1∙80) 0∙681 to 4 years 2/749 11/738 0∙17 (0∙04‐0∙78) 0∙009
Cardiac death or MI 0∙08≤1 year 11/857 11/850 1 00 (0 43 2 30) 0 99≤1 year 11/857 11/850 1∙00 (0∙43‐2∙30) 0∙991 to 4 years 3/779 11/781 0∙27 (0∙08‐0∙95) 0∙029
Clinically‐indicated TVR 0∙07≤1 year 13/857 15/850 0∙85 (0∙41‐1∙80) 0∙681 to 4 years 2/776 10/760 0∙19 (0∙04 0∙87) 0∙0171 to 4 years 2/776 10/760 0∙19 (0∙04‐0∙87) 0∙017
0∙1 0∙2 0∙5 1 2 4 6
Favours BES Favours SES
≤1 year
1 to 4 years
SYNERGY™ StentMeredith I et al. J Am Coll Card 2012
Bioabsorbable polymer (PLGA)(PLGA)
Applied only to the abluminal surface ( ll t)(rollcoat)
Thin strut PtCr Stent
Designed for polymer resorption within 4 months
PLGA BioabsorbablePolymer
Designed for polymer resorption within 4 months
+Everolimus
on Abluminal Side of Stentof Stent
Randomized Evaluation of a Novel Biodegradable Polymer‐Based Everolimus‐Eluting Coronary Stent
1°EP: In-Stent Late Loss
Polymer‐Based Everolimus‐Eluting Coronary StentMeredith I et al. J Am Coll Card 2012
Target Lesion Failure1 EP: In Stent Late Loss @ 6 Months
P=0 19
Target Lesion Failure @ 6 Months
0.5
0.6P=0.19
P=0.568
10 P=1.00
P=0.72
0 3
0.4
ss, m
m
4 1
6
ents
, %0.2
0.3
Late
lo
3.12.2
4.1
2
4Patie
0.15 0.10 0.130.0
0.1
SYNERGYPROMUS SYNERGY 0
2
PROMUS SYNERGY SYNERGY½ DoseElement™ PE SYN SYN ½Element ½ Dose
(N=98) (N=94) (N=99) (N=98) (N=94) (N=99)
6‐month versus 24‐month DAPT after PCIValgimigli M et al Circulation 2012
1°EP D h MI CVA T II III V BARC Bl di
Valgimigli M et al. Circulation 2012
1°EP: Death, MI, or CVA@ 2 Years
Type II, III, or V BARC Bleeding@ 2 Years
% %
12
14
12
14P=0.91
% %P=0.00018
10 10.1
8
10
7.48
10 HR 0.46 (95% CI 0.10-0.69)
4
6
3 54
6
2
4 3.5
2
4
0
6-month DAPT 24-month DAPT0
6-month DAPT 24-month DAPT
Impact of DAPT Discontinuation on Definite or Probable Stent Thrombosis with Everolimus‐ and
Kedhi E presented at ACC 2012
Probable Stent Thrombosis with Everolimus and Paclitaxel‐Eluting Stents Through 2 Years
Kedhi E. presented at ACC 2012
A Pooled Analysis of SPIRIT II, III, IV, and COMPARE Trials
6.2%6%
8%
EESPES
p for trend = 0.75p for trend = 0 05
4%
6% PES p for trend = 0.05
2.3% 2.3%
1 5%2%
4%
1.1%0.5% 0.5%
0.8%1.5%
0%
2%
Time of DAPT Discontinuation
1 to 6months
6 to 12months
12 to 24months
NOdiscontinuation
PolymerPolymer‐‐Free DES Free DES PlatformsPlatformsYUKON BioFreedom CRE8
DFS Technology Amazon PaxDFS Technology Amazon Pax
Polymer‐Free Biolimus‐A9 Coated StentTada N et al. Circ Cardiovasc Interv 2010;3:174‐83
90%
100%
Biolimus A9 Elution from Stents
(MEDIUM: PBS pH 7.4/Tween, 37°C)
Biolimus A9
20%
30%
40%
50%
60%
70%
80%
Cum
ulat
ive
Rel
ease
(%)
Bi
Struts With Fibrin Inflammation Score Struts With Giant Cells
0%
10%
0 5 10 15 20 25 30 35 40 45 50Time (Hrs)
78
961000.86
0 8
18.7
8
10
Struts With Fibrin Inflammation Score Struts With Giant Cells
51
78
60
80
% %0.6
0.8
6
8
20
40% %
0.28 0.31
0.2
0.42.9 2.6
2
4
0
BMS BioFreedom SES
0
BMS BioFreedom SES
0
BMS BioFreedom SES
Polymer Free AmphilimusPolymer Free Amphilimus‐‐Eluting Cre8™ StentEluting Cre8™ StentCRE8 Release KineticPolymer Free Abluminal Reservoir Technology
Bio Inducer Surface(i‐Carbofilm)
Amphilimus Formulation(Sirolimus + Organic Acid)(i‐Carbofilm) (Sirolimus + Organic Acid)
Pre Clinical In-Vivo AAssessment
Moretti et al. EuroIntervention 2011
Cre8™ Stent versus Cre8™ Stent versus PaclitaxelPaclitaxel‐‐Eluting StentEluting StentCarrié D et al. J Am Coll Cardiol 2012
Cardiac Death, MI, or TLR @ 12 Months
1°EP: In-stent Late Loss@ 6 Months
8%
P=0 81
Diabetic SubgroupOverall
0 4
0.5P<0.0001mm
0 4
0.5
0.43±0.41
P=0.0002
6.16.8
6
P=0.81
0.3
0.4
0.3
0.4
0.34±0.40
4
6
0 1
0.20.2
0.14±0.36 0 12±0 29 2
4
0
0.1
0
0.10.12±0.29
0
2
Cre8 TAXUS Libertè
(N=141) (N=135)
0
Cre8 TAXUS Libertè
(N=42) (N=33)
0Cre8 TAXUS Libertè
(N=148) (N=148)
Biodegradable Vascular Scaffolds (BVS)
1996
Van der Giessen Circulation
TamaiCirculation
OrmistonLancet
ErbelLancet
2000 2007 2008
JabaraPCR 2009
2009
AbizaidTCT 2009
HaudePCR 2011
20111996
AMS-1
2000 2007 2008 2009
IDEAL BDS DREAMS
2011
Animal studiespolymeric scaffoldsrevealing excessive
AMS-1first bioabsorbablemetallic non drug-
eluting scaffoldN=64
Polyanhidrideester and salicylic acid,
drug-eluting scaffoldN=11
DREAMSfirst drug-eluting
bioabsorbablemetallic scaffold
N=22ginflammatory reactions
Igaki TamaiFirst fully
Bioresorbable vascular scaffold
N=64
REVAPolycarbonate stent,
radiopaque non drug-
N 22
First fully biodegradable non
drug eluting scaffold N=15
vascular scaffoldfirst bioabsorbable drug
eluting scaffoldN=31
radiopaque, non drug-eluting scaffold
N=31
Fully Fully BioabsorbableBioabsorbable EverolimusEverolimus‐‐Eluting StentEluting StentO i t J t l L t 2008 371 899 907Ormiston J et al. Lancet 2008;371:899-907
Everolimus/PLLA MatrixMatrix Thin coating layer-1:1 ratio of Everolimus/PDLLA-Controlled drug releasereleasePLLA stent backbone-stent integrity-semicrystallinepolymer
Device success: 94% MACE(TLR):3.3% ST: 0% @ 12 months
Late loss (in-stent): 0.44±0.35 mm
Cumulative Cumulative Late Lumen Loss Among ABSORB Late Lumen Loss Among ABSORB Cohort B Cohort B
Serruys PW. Presented at TCT 2011
and and Patients Treated With Patients Treated With EverolimusEverolimus‐‐Eluting StentsEluting Stents
ABSORB Vasomotor Function Testing Through 2 Years
1 6 Months1 12 Months2 24 Months3
)
1
(N=15)
6 Months1
(N=6) (N=19)
12 Months2
(N=13) (N=9)
24 Months3
(N=7)
ion
Cohort B1 Cohort B2 Cohort A
n)
eter
(mm
)
0.5
Vaso
dila
ti
-dru
g in
fusi
on
sel D
iam
e
0
ctio
n
usio
n to
pos
t-
Δin
Ves
-0.5
Vaso
cons
tric
(pre
-dru
g in
fu
MethergineAcetylcholine
-1
V
2. Adapted from Serruys, PW. ACC 20111. Adapted from Serruys, PW. ACC 2011
3. Adapted from Serruys, PW, et al. Lancet 2009; 373: 897-910.
BIOSOLVEBIOSOLVE‐‐I IVUS Results at 6I IVUS Results at 6‐‐month month Waksman R presented at CRT 2012
Post implantation 6-month Follow-upScaffoldDegradation
Waksman R. presented at CRT 2012
Contribution to lumen loss
Loss of scaffolding area
In-stentneointima
53% 47%
0.38 mm 0.26 mm0.64 mm LLL
0.57 mm 0.51 mm1.08 mm LLL
47%
PROGRESS**
BIOSOLVE-I 0.64 mm LLL
33% less 49% less41% less
BIOSOLVE I
* N= 12 evaluable IVUS runs (volumetric) available at 6-month follow-up for cohort 1**Erbel R. et al., Lancet 2007;369:1869-75,
Waksman et.al, JACC Cardiovasc Intervent 2009;2:312-320
Newer Generation Drug‐Elutingg gStents…What Have We Achieved?
Improved safety• Reduced risk of stent thrombosis• Reduced risk of cardiac death or MI associated with ST
Improved efficacyR d d i k f TLR• Reduced risk of TLR
Decreased need for DAPTDecreased need for DAPT• Near elimination stent thrombosis associated with DAPT
discontinuation
Questions for TomorrowQuestions for Tomorrow
• Is a very short (<6 months) DAPT safe?• Are newer generation DES safer than BMS?Are newer generation DES safer than BMS?• Are biodegradable polymer based DES
superior to newer generation durable polymersuperior to newer generation durable polymer based DES?
• Are polymer-free DES able to achieve equivalent clinical efficacy as polymer based DES?
• Will BVS outperform newer generation DES?p g