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Adjunctive Therapy for PCI. Neal Uren MD MRCP Department of Cardiology Royal Infirmary of Edinburgh. Determinants of Successful PCI. CLINICAL STATUS LV function Stable vs. unstable angina vs. MI LESION COMPLEXITY AHA/ACC class OPERATOR VOLUME ADJUNCTIVE THERAPY - PowerPoint PPT Presentation
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Adjunctive Therapy Adjunctive Therapy for PCIfor PCI
Neal Uren MD MRCPDepartment of Cardiology
Royal Infirmary of Edinburgh
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
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”
Pharmacological Pharmacological Adjunctive TherapyAdjunctive Therapy
Heparin
Aspirin
Clopidogrel
Glycoprotein IIb/IIIa inhibitors
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
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
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
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
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
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
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
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
* 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
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%
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
•
•
•
•
•
•
• 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%
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
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
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
MACE Post-StentingMACE Post-Stenting
Bhatt Dl et al, JACC 2002;39:9-14
30 Day Mortality Post-30 Day Mortality Post-StentingStenting
Bhatt Dl et al, JACC 2002;39:9-14
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
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)
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
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
EPILOG & Bleeding RiskEPILOG & Bleeding Risk
MACE in the CAPTURE trial by TnTMACE in the CAPTURE trial by TnT
Hamm CW et al, NEJM 1999;340:1623
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
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
EPISTENT Subgroup AnalysisEPISTENT Subgroup Analysis
Lancet 1998;352:87
EPISTENT Subgroup AnalysisEPISTENT Subgroup AnalysisReduction of Non-Q wave MIReduction of Non-Q wave MI
Lancet 1998;352:87
ESPRITESPRIT
ESPRITESPRIT
ESPRITESPRIT
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