Post on 03-Jan-2016
description
www.metcardio.org
Giuseppe Biondi ZoccaiGiuseppe Biondi Zoccai
University of Turin, Turin, ItalyUniversity of Turin, Turin, ItalyMETCARDIO, Turin, ItalyMETCARDIO, Turin, Italy
gbiondizoccai@gmail.comgbiondizoccai@gmail.com
BMS & Sanofi Aventis Sponsored Symposium: BMS & Sanofi Aventis Sponsored Symposium: State of art of dual antiplatelet therapy in State of art of dual antiplatelet therapy in ACSACS
Bologna, 25/9/2008 – 13.05-13.25Bologna, 25/9/2008 – 13.05-13.25
THE IMPORTANCE OF AN ADEQUATE RISK-BENEFIT
RATIO IN THE ANTIPLATELET TREATMENT OF ACS PATIENTS
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Thrombotic eventsThrombotic events BleedingBleeding
SCOPE OF THE PROBLEM
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Thrombotic eventsThrombotic events BleedingBleeding
SCOPE OF THE PROBLEM
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SCOPE OF THE PROBLEM
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LEARNING GOALS
• What is the risk and the impact of atherothrombotic events in ACS?
• What is the risk and the impact of bleeding events in ACS?
• How can we strike a balance between risk and benefit of antiplatelet therapy in ACS?
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LEARNING GOALS
• What is the risk and the impact of atherothrombotic events in ACS?
• What is the risk and the impact of bleeding events in ACS?
• How can we strike a balance between risk and benefit of antiplatelet therapy in ACS?
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IN OTHER WORDS… WHAT ELSE SHOULD I EXPECT FROM ATHEROTHROMBOSIS
AFTER THE INDEX EVENT?
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WHAT IS THE CLINICAL BURDEN OF ATHEROTHROMBOSIS?
DEATHSTROKE
MITVR
RE-HOSPITALIZATION
My main tool to avoid athero-thrombosis:
antithrombotic Rx
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ATHEROTHROMBOTIC EVENTS AFTER ADMISSION FOR AMI
Capewell et al,Heart 2006
www.metcardio.orgCapewell et al, Heart 2006Capewell et al,Heart 2006
ATHEROTHROMBOTIC EVENTS AFTER ADMISSION FOR UA
www.metcardio.orgAntman et al, JAMA 2000;284:835-42
PREDICTORS OF ATHERO-THROMBOTIC EVENTS: TIMI Score (n=7081)
* all-cause mortality, myocardial infarction, and severe recurrent ischemia prompting urgent revascularization
*
VARIABLEMULTI-
VARIABLE PODDS RATIO POINT
Age>65 years <0.001 1.75 1
>2 risk factors for CAD
0.003 1.54 1
Significant CAD <0.001 1.70 1
ST deviation 0.005 1.51 1
Severe angina 0.001 1.53 1
Aspirin in last week
0.006 1.74 1
Raised cardiac markers
<0.001 1.56 1
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Antithrombotictherapy &
(selectively)invasive
management
Stable angina
Unstableangina
Reperfusion(thrombolysis and/or PTCA)
Minutes Hours
DaysWeeks
STEMIUA/NSTEMIAtherothrombosisNew terms
Old terms
Plaque rupture
Non-Q MI Q-MI
EXTREMELY VARIABLE PATHOPHYSIOLOGY
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EXTREMELY VARIABLE IMPACT OF MYOCARDIAL INFARCTION: case study from the PURSUIT trial
Akkerhuis et al, Circulation 2002;105:554-556
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ON TOP OF THIS:VARIABILITY IN RESPONSE TO ANTITHROMBOTIC THERAPY
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VARIABILITY IN CLOPIDOGREL RESPONSEChange in ADP-Induced
Platelet Aggregation75 mg chronic dosing
Serebruany et al, J Am Coll Cardiol 2005 Hochholzer et al, Circulation 2005
Time from loading dose to cath (h)
Maximal aggregation 5 µmol/L ADP (%)following 600 mg loading dose
0 2 4 6 8 100
20
40
60
80
100
N=1001
Num
ber
of P
atie
nts N=544
Relative change in aggregation
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LEARNING GOALS
• What is the risk and the impact of atherothrombotic events in ACS?
• What is the risk and the impact of bleeding events in ACS?
• How can we strike a balance between risk and benefit of antiplatelet therapy in ACS?
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IN OTHER WORDS…WHEN IS MUCH TOO MUCH?
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THE CASE FOR FOCUSING ON BLEEDING
• It is common
• It is expensive
• Patients remember bleeding events more than asymptomatic enzyme leaks
• It is associated with increased mortality
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THE CASE FOR FOCUSING ON BLEEDING
• It is common
• It is expensive
• Patients remember bleeding events more than asymptomatic enzyme leaks
• It is associated with increased mortality
• Strategies that prevent or reduce bleeding may reduce mortality
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THE CASE FOR FOCUSING ON BLEEDING
• It is common
• It is expensive
• Patients remember bleeding events more than asymptomatic enzyme leaks
• It is associated with increased mortality
• Strategies that prevent or reduce bleeding may reduce mortality
• Minimizing bleeding should be an essential part of modern therapy of CAD
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PREVALENCE OF MAJOR BLEEDING: GRACE Registry (n=24045)
Moscucci et al, Eur Heart J 2003;24:1815-1823
www.metcardio.orgMoscucci et al, Eur Heart J 2003;24:1815-1823
PREDICTORS OF MAJOR BLEEDING: GRACE Registry (n=24045)
www.metcardio.orgRao et al, Am J Cardio 2005;96:1200-1206
IMPACT* ON MORTALITY OF BLEEDING IN ACS
Sur
viva
l P<0.0001
P=0.20
P<0.0001
*at both univariate and multivariable analyses
www.metcardio.orgAronson et al, Am J Cardiol 2008;102:115-119
SIMILAR PREDICTORS AND IMPACT* FOR BLOOD TRANSFUSIONS IN AMI
*at both univariate and multivariable analyses
www.metcardio.orgCohen et al, J Am Coll Cardio 2004;44:1792-1800
EVENT COST (USD) P VALUE
Myocardial infarction>10 x ULN5-10 x ULN3 x ULN
4,084 2,233 1,165
<0.05<0.05<0.05
Repeat revascularizationPCICABG
8,18729,506
<0.05<0.05
Stroke ? ?
Major bleeding 6,300 <0.05
IMPACT ON COSTS: case study from the REPLACE-2 trial
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LEARNING GOALS
• What is the risk and the impact of atherothrombotic events in ACS?
• What is the risk and the impact of bleeding events in ACS?
• How can we strike a balance between risk and benefit of antiplatelet therapy in ACS?
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OVERWHELMING COMPLEXITY?
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FINDING THE BALANCE: AN EASY CASE
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FINDING THE BALANCE: ANOTHER EASY CASE
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WHAT ABOUT TOUGHER CASES?
www.metcardio.orgNdrepepa et al, J Am Coll Cardiol 2008;51:690-7
RATIONALE FOR QUADRUPLE END-POINT IN PCI
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RATIONALE FOR QUADRUPLE END-POINT IN PCI
Ndrepepa et al, J Am Coll Cardiol 2008;51:690-7
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DEFINITION OF NET ADVERSE CLINICAL EVENTS (NACE)
Ndrepepa et al, J Am Coll Cardiol 2008;51:690-7
DEATHDEATH
MIMI
STROKESTROKE
PCI/ CABGPCI/ CABG
MAJOR MAJOR BLEEDINGBLEEDING
ALL CAN ALL CAN IMPACT ON IMPACT ON
PROGNOSIS, PROGNOSIS, SYMPTOMS, SYMPTOMS, AND COSTS!AND COSTS!BUT EACH BUT EACH
MAY IMPACT MAY IMPACT THESE IN THESE IN
DIFFERENT DIFFERENT DIRECTIONSDIRECTIONS
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DEFINITION OF NET ADVERSE CLINICAL EVENTS (NACE)
*in several cases, stroke is not included in NACE definition
DEATHDEATH
MIMI
STROKESTROKE
PCI/ CABGPCI/ CABG
MAJOR MAJOR BLEEDINGBLEEDING
ALL CAN ALL CAN IMPACT ON IMPACT ON
PROGNOSIS, PROGNOSIS, SYMPTOMS, SYMPTOMS, AND COSTS!AND COSTS!BUT EACH BUT EACH
MAY IMPACT MAY IMPACT THESE IN THESE IN
DIFFERENT DIFFERENT DIRECTIONSDIRECTIONS
NACE: composite of all cause death, non-fatal myocardial infarction, non-fatal stroke,
PCI/CABG, and non-fatal major bleeding*
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WHAT ABOUT CLOPIDOGREL IN REAL LIFE ?
Alexander et al, Am Heart J 2008;156:606-612
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SUMMARY OF EVIDENCE ON CLOPIDOGREL LOADING
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SUMMARY OF EVIDENCE ON CLOPIDOGREL LOADING
Lotrionte et al, Am J Cardio 2007;100:1199-1206
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DO-IT-YOURSELF ANTIPLATELET THERAPY?
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DO-IT-YOURSELF ANTIPLATELET THERAPY!
Bonello et al, J Am Coll Cardiol 2008;51:1404-11
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DO-IT-YOURSELF ANTIPLATELET THERAPY!
Bonello et al, J Am Coll Cardiol 2008;51:1404-11
26 patients receiving 4 600 mg loading doses of clopidogrel
24 hours apart (2.4 g)!
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A GLIMPSE AT THE FUTURE
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TAKE HOME MESSAGES
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1. A COMPREHENSIVE APPRAISAL OF THROMBOTIC & BLEEDING RISKS IS NEEDED IN PATIENTS WITH ACS
THROMBOSIS
BLEEDING
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2. BETTER YET PRACTICAL RISK-STRATIFICATION TOOLS FOR BLEEDS AND THROMBOSES ARE WARRANTED
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3. EVERY PATIENT WILL HAVE AN INDIVIDUALIZED TREATMENT, DEPENDING ON OVERALL RISK PROFILE AND ACUITY
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For further slides on these topics please feel free to visit the metcardio.org website:
http://www.metcardio.org/slides.html