Adjunctive Therapy for PCI Neal Uren MD MRCP Department of Cardiology Royal Infirmary of Edinburgh.
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Transcript of Adjunctive Therapy for PCI Neal Uren MD MRCP Department of Cardiology Royal Infirmary of Edinburgh.
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Adjunctive Therapy Adjunctive Therapy for PCIfor PCI
Neal Uren MD MRCPDepartment of Cardiology
Royal Infirmary of Edinburgh
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Determinants of Successful Determinants of Successful PCIPCI
CLINICAL STATUSCLINICAL STATUS LV function Stable vs. unstable angina vs. MI
LESION COMPLEXITYLESION COMPLEXITY AHA/ACC class
OPERATOR VOLUMEOPERATOR VOLUME
ADJUNCTIVE THERAPYADJUNCTIVE THERAPY Stenting (BENESTENT, STRESS) Anti-thrombotic and anti-platelet agents
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RationaleRationale
““Although it is not yet possible to Although it is not yet possible to pharmacologically modify the risk pharmacologically modify the risk of balloon-mediated intimal and of balloon-mediated intimal and medial disruption, it is possible medial disruption, it is possible
to modify chemically the platelet-to modify chemically the platelet-fibrin response to vascular injury fibrin response to vascular injury in order to influence the outcome in order to influence the outcome
of the procedure”of the procedure”
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Pharmacological Pharmacological Adjunctive TherapyAdjunctive Therapy
Heparin
Aspirin
Clopidogrel
Glycoprotein IIb/IIIa inhibitors
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UK Interventional UK Interventional Practice 1999Practice 1999
Structured questionnaire
68% response over 4 months
53% ≥10,000 U heparin
8.3% abciximab use
82% clopidogrel use
Swanson N et al, Int J Cardiol 2001;79:119-125
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HeparinHeparin Lower incidence of complications in unstable angina
patients pre-treated with iv heparin Lukas MA et al, JACC 1988;11:132A(abstr)
Close temporal relationship between discontinuation of anticoagulation after PTCA and coronary occlusion Gabliani G et al, AHJ 1988;116:696-700
10,000 U iv heparin = ACT <300s in 5% of stable and 15% of unstable patients Dougherty KG et al, CCD 1992;26:260-3
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Defining the Optimal ACTDefining the Optimal ACT with UF Heparinwith UF Heparin
Meta-analysis of 6 trials with UFH as control
n=5216, with patients in 25 s intervals
Endpoint of 7 day MACE + major/minor bleeds
ACT 350-375 s 6.6% vs ACT 171-295 s 8.8% (p<0.01)
ACT should be substantially higher than currently appreciated
Chew DP et al, Circulation 2001;103:961-6
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Low Dose Heparin Low Dose Heparin (30 U/kg)
n=418 patients
Mean age 63±11 years
2253±1056 U/l with a final ACT of 174±69 s
Manual compression for 7.7±3 minutes
Average procedure time of 25±16 minutes
MACE 2.9% at discharge
0.24% serious vascular complications Godon P et al, Arch Mal Coeur Vaiss
2001;94:984-8
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Low Molecular Weight Low Molecular Weight HeparinHeparin
Elective PCI
NICE 1 = enoxaparin 1.0 mg/kg iv
NICE 4 = enoxaparin 0.75 mg/kg iv with standard abciximab
Comparable incidence of bleeding and ischaemic complications in NICE 4 compared with UFH + abciximab
Kereiakes DJ et al, J Invas Cardiol 2001;13:272-8
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Low Molecular Weight Low Molecular Weight Heparin Heparin
2 doses of Dalteparin + abciximab (n=57)
0
2
4
6
8
10
12
Procedural thrombosis Major bleeding
40 U/kg60 U/kg
Kereiakes DJ et al, Am Heart J 2001;141:348-52
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AspirinAspirin No difference in outcome between 80 mg and
1500 mg started 24 h pre-PCI Mufson L et al, JACC
1988;11:236A(abstr)
No additional benefit of dipyridamole Lembo NJ et al, AJC 1990;65:422-6
No benefit from single dose ASA pre-PCI
Patrono C et al, Circulation 1985;72:1177-84
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Ticlopidine Study TrialTiclopidine Study Trial
0
2
4
6
8
10
12
14 Placebo
ASA 325mg2 +Persantin 75 mg3
Ticlopidine 250 mg3
Perc
en
tag
e
Ischaemic complications after 4-5 days pre-treatment
White CW et al, Circulation 1987;76:IV-400
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* p=0.06
Platelet Aggregability Platelet Aggregability Post-PCIPost-PCI
0
20
40
60
80
100
120
Pre Post
ASA+Ticlid PTCAASA Coronary angio
**
p=0.06p=0.03
Tim
e t
o o
cclu
sion
(s)
Greateraggregability
Fischetti D et al, J Thromb Thrombolysis 2001;10:265-9
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De-evolution of Stent De-evolution of Stent ThrombosisThrombosis
1986-91 Serruys et al/Schatz et al~25%1991 10 pooled studies4.5%1993 Stress/Benestent/TASC 1 3.7%1994 Colombo et al
0.9%1995 MUST Registry
1.6%1996 MUSIC Registry
0.6%1997 Moussa et al1.9%
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Risk of MACE After Successful StentingRisk of MACE After Successful Stenting
• • • • •• • • •
• AgeAge • DiabetesDiabetes• Acute MI (<72h)Acute MI (<72h)• Unstable anginaUnstable angina• Impaired LVImpaired LV• Stented length• Residual dissection• Stent overlapStent overlap •Use of ticlopidine*
Schülen et al, Circulation 1998;98:104-111
0.1 1.0 10 200.1 1.0 10 20Hazard Ratio & 95% CIHazard Ratio & 95% CI
n=2894n=2894105 events105 events
* 80% ASA+Ticlidopine
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•
•
•
•
•
•
• CFX or SVGCFX or SVG • Vessel sizeVessel size• Stenosis gradeStenosis grade• Stenosis lengthStenosis length• Acute occlusion pre-stentAcute occlusion pre-stent• Experience Experience (yrs)(yrs)
0.1 1.0 10 200.1 1.0 10 20
Odds Ratio & 95% CIOdds Ratio & 95% CI
Risk of a Procedural FailureRisk of a Procedural Failure
Schülen et al, Circulation 1998;98:104-111
Procedure failure = MACE 42.6%, procedure success = MACE 3.6%
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The STARS Trial
0
1
2
3
4
5
6
7
Stent Thrombosisat 30 days
Haemorrhagiccomplications
AspirinAspirin+WarfarinAspirin +TiclopidineP
erc
en
tag
e
*
* p<0.001 vs. others
*
1965 patients50 centres
84% angio. success
Leon MB et al, NEJM 1998;339:1702-4
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The STARS Trial Suboptimal Stent Registry
0123456789
30 day stentthrombosis
30 daymortality
Peri-procedure
NQWMI
Optimal (<10%DS)Suboptimal
265 patients16% vs.27% 9/12 CRS*
**
* p<0.01
Perc
en
tag
e
Cutlip DE et al, JACC 1999;34:698-706
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Clopidogrel vs. Ticlopidine Clopidogrel vs. Ticlopidine Post-PCIPost-PCI
No one trial large enough to demonstrate comparability
n=13,995 meta-analysis 1° endpoint of MACE at 30 days after
stenting MACE clopidogrel = 2.1% vs MACE ticlopidine =
4.0% Death clopidogrel = 0.48% vs death ticlopidine
= 1.1%
Bhatt Dl et al, JACC 2002;39:9-14
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MACE Post-StentingMACE Post-Stenting
Bhatt Dl et al, JACC 2002;39:9-14
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30 Day Mortality Post-30 Day Mortality Post-StentingStenting
Bhatt Dl et al, JACC 2002;39:9-14
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Duration of TherapyDuration of TherapyRetrospective analysis of ticlopidine post-stentn=56782.0% stent failure at 2 weeks + 0.5% at 2-4 weeks Risk factors for late events (2.5% if all 3
present)
- age- reduced LV function- hypertension
4 weeks theinopyridine therapy preferable
Schülen H et al, JACC 37:2066-73
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Timing of TherapyTiming of Therapy
Ticlopidine >24 h pre-PCI cause significant platelet inhibition
Maximum effect at 3-5 days van de Loo A et al, Eur Heart J
1998;19:96-102
Ticlopidine pre-treatment duration ~ reduced NQWMI
Steinbuhl S et al, JACc 1998;32:1366-70
Clopidogrel induces platelet inhibition within 30 min
MACE ~ no pre-treatment (T / C) [OR 3.5]
Steven P et al, JACC 2001;38:648A (abstr)
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n=2099 n=2972 n=1265
Glycoprotein IIb/IIIa Receptor Glycoprotein IIb/IIIa Receptor InhibitionInhibition
30 day MACE with Abciximab30 day MACE with Abciximab
0PlaceboReopro B+I
EPICEPIC EPILOGEPILOG CAPTURECAPTUREHigh-risk PCI Refractory
USA pre-PCI
0
5
10
15
20
15.9%
11.3%
2
4
6
8
10
12
14
12.8%
8.3%
NEJM1994;330:957 NEJM 1997;336:1689 Lancet 1997;349:1429
11.7%
5.3%
Perc
en
tag
e
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Low dose heparin = 70 U/kg for ACT≥200 s
Stnadard dose heparin = 100 U/kg for ACT≥300 s
EPILOG & Bleeding RiskEPILOG & Bleeding Risk
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EPILOG & Bleeding RiskEPILOG & Bleeding Risk
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MACE in the CAPTURE trial by TnTMACE in the CAPTURE trial by TnT
Hamm CW et al, NEJM 1999;340:1623
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63 centres in North America 2399 patients undergoing PCI 36% unstable angina <48h 57% unstable angina <6 months 16% recent MI (<7 days) 20% diabetics Reopro 60 min pre-PCI, 12 h post-PCI
Lancet 1998;352:87
The EPISTENT TrialThe EPISTENT Trial
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EPISTENT at 30 Days and 12 MonthsEPISTENT at 30 Days and 12 Months
0
5
10
15
20
30 day
MACE
Stent + placebo
Stent + abciximab
Balloon + abciximab
TVR
1 year
* p<0.01, ° p<0.05
Death/MI
**
*°
*
%
Death/MI/Urgent Revascularisation
Lancet 1998;352:87
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EPISTENT Subgroup AnalysisEPISTENT Subgroup Analysis
Lancet 1998;352:87
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EPISTENT Subgroup AnalysisEPISTENT Subgroup AnalysisReduction of Non-Q wave MIReduction of Non-Q wave MI
Lancet 1998;352:87
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ESPRITESPRIT
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ESPRITESPRIT
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ESPRITESPRIT
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Heparin - lower doses acceptable (?<5000 U)
Pre-treatment with aspirin essential Clopidogrel pre- & post-stenting GpIIb/IIIa receptor inhibitors - Reopro™
reduces CK release in stable angina No substitute for optimal stent
deployment
ConclusionsConclusions