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

gbiondizoccai@gmail.comgbiondizoccai@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

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