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Antiplatelet therapy and PCI in Antiplatelet therapy and PCI in
unstable angina and NSTEMIunstable angina and NSTEMI
Giuseppe Biondi ZoccaiGiuseppe Biondi Zoccai
Divisione di Cardiologia, Università di TorinoDivisione di Cardiologia, Università di Torino
[email protected]@gmail.com
DisclosureDisclosure
• No funding or conflict of interest to declare
TopicsTopics
• Introduction and pathophysiologic
insights
• Antiplatelet regimens
• Triage to invasive management
• State of the art PTCA
TopicsTopics
• Introduction and pathophysiologic
insights
• Antiplatelet regimens
• Triage to invasive management
• State of the art PTCA
Antithrombotictherapy &
(selectively)invasive
management
Stable angina
Unstableangina
Reperfusion(thrombolysis and/or PTCA)
Minutes Hours
DaysWeeks
STEMIUA/NSTEMIAtherothrombosisNew terms
Old terms
Plaque Plaque rupturerupture
Non-Q MI Q-MI
Acute coronary syndromesAcute coronary syndromes
Scope of the problemScope of the problemThrombotic eventsThrombotic events
Myocardial Myocardial ischemiaischemia
BleedingBleeding
Peri-procedural Peri-procedural complicationscomplications
Scope of the problemScope of the problemThrombotic eventsThrombotic events
Myocardial Myocardial ischemiaischemia
BleedingBleeding
Peri-procedural Peri-procedural complicationscomplications
Scope of the problemScope of the problem
Scope of the problem: AMIScope of the problem: AMI
Capewell et al, Heart 2006
Scope of the problem: Scope of the problem: unstable anginaunstable angina
Capewell et al, Heart 2006
Pathways to thrombosisPathways to thrombosis
****
** **Myers, BUMC Proceedings 2005
Multiple vulnerable coronary Multiple vulnerable coronary
plaques in patients with AMIplaques in patients with AMI
Asakura et al, J Am Coll Cardiol 2001
Multiple ruptured coronary Multiple ruptured coronary
plaques in patients with ACSplaques in patients with ACS
Endothelialization of stent strutsEndothelialization of stent struts
Guagliumi et al, Ital Heart J 2003
SES BMS
TopicsTopics
• Introduction and pathophysiologic
insights
• Antiplatelet regimens
• Triage to invasive management
• State of the art PTCA
0.00
0.05
0.10
0.15
0.20
0.25
0 3 6 9 12
Months
Pro
bab
ility
of
de
ath
or
MI Placebo
ASA 75 mg
Risk ratio after 1 year 0.5295% Cl 0.37–0.72 (P=0.0001)
Wallentin et al, JACC 1991
Aspirin in unstable anginaAspirin in unstable angina
3,7
1,7
0
1
2
3
4
Serious bleeding
(%)
ASA+UFH ASA
Theroux et al, NEJM 1988
UF Heparin in NSTEACSUF Heparin in NSTEACS
LMW heparin in NSTEACSLMW heparin in NSTEACS
Cu
mu
lati
ve h
azar
d r
ates
fo
r C
V d
eath
/MI
Days of follow-up
a = median time PCI (10 days)b = 30 days after median time of PCI
0.15
0.10
0.05
0.0
1000
40 100 200 300 400
a b
PlaceboClopidogrelClopidogrel
12.6%
8.8%
1.9% ARR31% RRRP=0.002N=2,658
Mehta et al, Lancet 2001
PCI-CURE SubstudyPCI-CURE Substudy
Cuisset et al, JACC 2006
*P=0.02
N=146
N=146
1-M
on
th
Clopidogrel loading in pts Clopidogrel loading in pts with ACS undergoing PCIwith ACS undergoing PCI
Kastrati et al, JAMA 2006
Benefits of abciximab in ACS patients Benefits of abciximab in ACS patients pretreated with 600 mg clopidogrelpretreated with 600 mg clopidogrel
*Death/MI/urgent TVR
*
600 mg clopidogrel500 mg ASA
>2 h before PCI
13,800 pts
Endpoint: Death/MI/urgentTVR
Bivalirudin in ACS: the ACUITY TrialBivalirudin in ACS: the ACUITY Trial
Stone et al, TCT 2006
ESC guidelinesESC guidelines
2002 ESC guidelines on NSTEACS2002 ESC guidelines on NSTEACS
Bertrand et al, EHJ 2002
Bertrand et al, EHJ 2002
2002 ESC guidelines on NSTEACS2002 ESC guidelines on NSTEACS
Silber et al, EHJ 2005
2005 ESC guidelines on PCI2005 ESC guidelines on PCI
Overwhelming complexity?Overwhelming complexity?
Bertrand et al, EHJ 2002; Silber et al, EHJ 2005
ESC guidelines: a synthesisESC guidelines: a synthesis• ASPIRIN:ASPIRIN: 500 mg oral or 300 mg IV loading dose, followed by 75-100
mg daily lifelong
• CLOPIDOGREL:CLOPIDOGREL: 300 to 600 mg loading dose ASAP, followed by 75 mg daily for 9-12 months
• DIRECT THROMBIN INHIBITORS:DIRECT THROMBIN INHIBITORS: as replacement of UFH or LWM for heparin-induced thrombocytopenia, or in patients at high-risk of bleeding but low risk of procedural ischemic events
• GPIIB/IIIA INHIBITORS:GPIIB/IIIA INHIBITORS: routinely in high-risk patients, provisionally in others (abciximab or eptifibatide in the cath lab if immediate [<2.5 h] angio or provisional use; eptifibatide or tirofiban if early [<48 h] angio)
• LOW MOLECULAR WEIGHT HEPARINLOW MOLECULAR WEIGHT HEPARIN (eg 10 mg/Kg SC enoxaparin twice daily): if invasive strategy is not applicable or deferred
• UNFRACTIONED HEPARIN:UNFRACTIONED HEPARIN: 50-100 IU/Kg IV bolus and additional doses aiming for target ACT (250–350 s without GpIIb/IIIa inhibitors, and 200–250 with them) if immediate or early invasive strategy
TopicsTopics
• Introduction and pathophysiologic
insights
• Antiplatelet regimens
• Triage to invasive management
• State of the art PTCA
Inferiority of invasive therapy?Inferiority of invasive therapy?If PTCA:- routine stenting- bolus + infusion abciximab
Medical Rx:- 300 mg aspirin (then >75 mg)
- 300 mg clopidogrel (then 75 mg)
- 80 mg atorvastatin- 1 mg/Kg enoxaparin
Reconciling current evidenceReconciling current evidence
Reconciling current evidenceReconciling current evidence
Less late PTCA/CABG
Improved (long-term)
survival
But potential increase in peri-procedural
infarctions
Bavry et al, JACC 2006
Invasive vs conservative Rx: impact Invasive vs conservative Rx: impact of stents and antiplatelet treatmentsof stents and antiplatelet treatments
TopicsTopics
• Introduction and pathophysiologic
insights
• Antiplatelet regimens
• Triage to invasive management
• State of the art PTCA
Agostoni et al, JACC 2004
Significantly lower bleedings with radial vs femoral approach PCI
(P=0.05), even selecting studies with ACS patients only (N=291)
Benefits of the radial approachBenefits of the radial approach
Burzotta et al, AJC 2003
Benefits of direct stentingBenefits of direct stenting10 trials with 2576
patients randomized to direct stenting
(DS) vs conventional stenting (CS)
Odds ratio=0.57 (0.35-0.95), P<0.001
Lemos et al, JACC 2003
Safety of sirolimus-eluting Safety of sirolimus-eluting
stents in patients with ACSstents in patients with ACS
Moses et al, JACC 2005
Safety of paclitaxel-eluting Safety of paclitaxel-eluting
stents in patients with ACSstents in patients with ACS
Urban et al, Circ 2006
Predictors of DES thrombosisPredictors of DES thrombosis
Nordmann et al, EHJ 2006
Potential hazards of DESPotential hazards of DES
Take home messagesTake home messages
• Timely triage and administration of standard antithrombotic therapies is pivotal in NSTEACS (ie aspirin, clopidogrel, and heparin [LMW or UFH])
• Glycoprotein IIb/IIIa inhibitors can be administered upstream or directly in the cath lab, and are indicated in high-risk patients
• The role of direct thrombin inhibitors is still to be defined, even if a trade-off between bleeding/peri-procedural MI is likely
• Default invasive or selectively invasive strategies with ad hoc PTCA are both acceptable, as long as the threshold for medical therapy failure remains low
• Choice between DES and BMS is best individualized
Take home messagesTake home messages
For further slides on these topics please feel free to visit the
metcardio.org website:
http://www.metcardio.org/slides.html