ACS-WRAP
description
Transcript of ACS-WRAP
ACS-WRAPACS-WRAP
Charles V. Pollack, Jr., M.A., M.D., FACEP, FAHA
Professor and Chairman
Emergency Medicine, Pennsylvania Hospital
University of Pennsylvania Health System
Philadelphia
Charles V. Pollack, Jr., M.A., M.D., FACEP, FAHA
Professor and Chairman
Emergency Medicine, Pennsylvania Hospital
University of Pennsylvania Health System
Philadelphia
Non-ST-Segment-Elevation ACSNon-ST-Segment-Elevation ACS
Inclusive of unstable angina and NSTEMI
These are the same clinical syndrome, with the only distinction being the objective identification of myonecrosis with NSTEMI
Neither UA or NSTEMI are necessarily associated with ischemic ECG changes Result from partial or intermittent obstruction
of epicardial vessels, or complete obstruction of distal branches
In contradistinction, STEMI is complete obstruction of larger vessel, which is associated with ECG changes
Inclusive of unstable angina and NSTEMI
These are the same clinical syndrome, with the only distinction being the objective identification of myonecrosis with NSTEMI
Neither UA or NSTEMI are necessarily associated with ischemic ECG changes Result from partial or intermittent obstruction
of epicardial vessels, or complete obstruction of distal branches
In contradistinction, STEMI is complete obstruction of larger vessel, which is associated with ECG changes
Non-ST-Segment-Elevation ACSNon-ST-Segment-Elevation ACS
UA/NSTEMI typically result from fissure or frank rupture of an atherosclerotic plaque Stimulates local activation of:
• platelets• coagulation cascade• complement
Platelet aggregate forms over site of plaque injury . . . but remains unstable and subject to shear forces from passing blood flow
No obstruction in situ, but downstream embolization can occur• perhaps resulting in ST↓ or troponin leak
UA/NSTEMI typically result from fissure or frank rupture of an atherosclerotic plaque Stimulates local activation of:
• platelets• coagulation cascade• complement
Platelet aggregate forms over site of plaque injury . . . but remains unstable and subject to shear forces from passing blood flow
No obstruction in situ, but downstream embolization can occur• perhaps resulting in ST↓ or troponin leak
Non-ST-Segment-Elevation ACSNon-ST-Segment-Elevation ACS
Pharmacologic therapy in NSTE ACS is therefore directed at this triad of abnormal activity: Platelet activation—anti-activation and anti-
aggregation• ASA and clopidogrel• GPIs
Coagulation activation—anticoagulants Complement activation—anti-
inflammatories . . . ? statins
Pharmacologic therapy in NSTE ACS is therefore directed at this triad of abnormal activity: Platelet activation—anti-activation and anti-
aggregation• ASA and clopidogrel• GPIs
Coagulation activation—anticoagulants Complement activation—anti-
inflammatories . . . ? statins
Guidelines for NSTE-ACS diagnosis and management
Guidelines for NSTE-ACS diagnosis and management
Very complex disease state with broad ranges of risk and a multitude of therapeutic options
Many important and pertinent clinical studies
Information overload!
Need evidence-based guidelines to promote consistency of care and resulting better outcomes
Very complex disease state with broad ranges of risk and a multitude of therapeutic options
Many important and pertinent clinical studies
Information overload!
Need evidence-based guidelines to promote consistency of care and resulting better outcomes
Guidelines for NSTE-ACS diagnosis and management
Guidelines for NSTE-ACS diagnosis and management
AHCPR guidelines 1994: first attempt
ACC/AHA Joint Task Force: Sep 2000 Widely read, lots of interest Clear evidence scoring, sensible
recommendations, temporal sequencing• “soup to nuts”
Recapitulation, interpretation, and promulgation for upstream providers in Annals of Emergency Medicine
AHCPR guidelines 1994: first attempt
ACC/AHA Joint Task Force: Sep 2000 Widely read, lots of interest Clear evidence scoring, sensible
recommendations, temporal sequencing• “soup to nuts”
Recapitulation, interpretation, and promulgation for upstream providers in Annals of Emergency Medicine
Class I Benefit >>> Risk
Procedure/ Treatment SHOULD be performed/ administered
Class IIa Benefit >> RiskAdditional studies with focused objectives needed
IT IS REASONABLE to perform procedure/administer treatment
Class IIb Benefit ≥ RiskAdditional studies with broad objectives needed; Additional registry data would be helpful
Procedure/Treatment MAY BE CONSIDERED
Class III Risk ≥ BenefitNo additional studies needed
Procedure/Treatment should NOT be per-formed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL
shouldis recommendedis indicatedis useful/effective/
beneficial
is reasonablecan be useful/effective/
beneficialis probably
recommended or indicated
may/might be considered
may/might be reasonable
usefulness/effectiveness is unknown /unclear/uncertain or not well established
is not recommendedis not indicatedshould notis not useful/effective/
beneficialmay be harmful
Applying Classification of Recommendations
“The Guidelines”Weighing the Evidence
“The Guidelines”Weighing the Evidence
Weight of evidence grades:= Data from many large, randomized trials= Data from fewer, smaller randomized trials,
careful analyses of nonrandomized studies, observational registries
= Expert consensus
Weight of evidence grades:= Data from many large, randomized trials= Data from fewer, smaller randomized trials,
careful analyses of nonrandomized studies, observational registries
= Expert consensus
• Braunwald E, Antman EM, Beasley JW, et al: ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients with Unstable Angina). J Am Coll Cardiol 2000;36:970-1062 (2002 update at www.acc.org; summary in Circulation 2002;106:1893-1900)
• Pollack CV, Roe MT, Peterson ED: 2002 Update to the Pollack CV, Roe MT, Peterson ED: 2002 Update to the ACC/AHA guidelines for the management of patients with ACC/AHA guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial unstable angina and non-ST-segment elevation myocardial infarction: Implications for emergency department practice. infarction: Implications for emergency department practice. Ann Ann Emerg MedEmerg Med 2003;41:355-69. 2003;41:355-69.
NSTE ACS: Optimal Therapy, 2002-07NSTE ACS: Optimal Therapy, 2002-07
• Anderson JL, Adams CD, Antman EM, et al. 2007 guidelines for the management of patients with unstable angina/non-ST-segment-elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2007;50:e1-e157, and Circulation 2007;116:e148-e304, and at www.acc.org and at www.americanheart.org.
• Pollack CV, Braunwald E: 2007 Update to the ACC/AHA Pollack CV, Braunwald E: 2007 Update to the ACC/AHA guidelines for the management of patients with unstable guidelines for the management of patients with unstable angina and non-ST-segment elevation myocardial angina and non-ST-segment elevation myocardial infarction: Implications for emergency department practice. infarction: Implications for emergency department practice. Ann Emerg MedAnn Emerg Med 2008, in press. 2008, in press.
NSTE ACS: Optimal Therapy, 8/6/07NSTE ACS: Optimal Therapy, 8/6/07
CRUSADE: A National CRUSADE: A National
Quality Improvement InitiativeQuality Improvement Initiative
CRUSADE: A National CRUSADE: A National
Quality Improvement InitiativeQuality Improvement Initiative
CCan an RRapid Risk Stratification of apid Risk Stratification of UUnstable Angina Patients nstable Angina Patients
SSuppress uppress ADADverse Outcomes with verse Outcomes with EEarly Implementation arly Implementation
of the ACC/AHA Guidelinesof the ACC/AHA Guidelines
2002-20072002-2007
CCan an RRapid Risk Stratification of apid Risk Stratification of UUnstable Angina Patients nstable Angina Patients
SSuppress uppress ADADverse Outcomes with verse Outcomes with EEarly Implementation arly Implementation
of the ACC/AHA Guidelinesof the ACC/AHA Guidelines
2002-20072002-2007
January 2007
443 Participating Sites205,528 Patients
AK(0)
WA(5)
OR(5)
CA(34)
ID(0)
NV(2)
MT(0)
WY(0)
CO(9)
NM(1)
ND(1)
SD(3)
NE (3)
KS(3)
OK(7)
TX(13)
MN(3)
IA(6)
MO(8)
AR(2)
LA(6)
WI(5) MI
(20)
MI
UT(1)
AZ(8)
HI (0)
IL(17)
IN(7)
KY(8)
TN (9)
MS(6)
AL(9)
GA(14)
FL(31)
SC(7)
NC(14)
VA(17)
OH(35)
WV(2)
PA(36)
NY(34)
MD (13)
ME(0)
VT (1)
NH (1)
NJ (12)
MA (10)
CT (7)
DE (3)
RI (1)
DC (1)
The CRUSADE Experience
Data on file, Duke Clinical Research Institute.Data on file, Duke Clinical Research Institute.
Hospital Link Between Overall Guidelines Adherence and MortalityHospital Link Between Overall Guidelines Adherence and Mortality
Peterson et al, JAMA 2006;295:1863-1912Peterson et al, JAMA 2006;295:1863-1912
5.95
5.16 4.97
4.16
5.064.63
4.15
6.31
0
1
2
3
4
5
6
7
<=25% 25 - 50% 50 - 75% >=75%
Hospital Composite Quality Quartiles
% I
n-H
osp
Mo
rtal
ity
Adjusted Unadjusted
5.95
5.16 4.97
4.16
5.064.63
4.15
6.31
0
1
2
3
4
5
6
7
<=25% 25 - 50% 50 - 75% >=75%
Hospital Composite Quality Quartiles
% I
n-H
osp
Mo
rtal
ity
Adjusted Unadjusted
Every 10% Every 10% in guidelines adherence in guidelines adherence 10% 10% in mortality (OR=0.90, 95% CI: 0.84-0.97) in mortality (OR=0.90, 95% CI: 0.84-0.97)
Management Strategies: 2002 GuidelinesConservative vs. Invasive StrategiesConservative vs. Invasive Strategies
Management Strategies: 2002 GuidelinesConservative vs. Invasive StrategiesConservative vs. Invasive Strategies
Early (within 48h) invasive strategy in high-risk patients with any of the following:
- Recurrent ischemia, despite meds- Recurrent ischemia, despite meds
- Elevated Troponin I or T- Elevated Troponin I or T
- New ST-segment depression- New ST-segment depression
- New CHF symptoms- New CHF symptoms
- High-risk stress test findings- High-risk stress test findings
- LV dysfunction (EF < 40%)- LV dysfunction (EF < 40%)
- Hemodynamic instability, sustained VT- Hemodynamic instability, sustained VT
- PCI within 6 months, prior CABG- PCI within 6 months, prior CABG
Early (within 48h) invasive strategy in high-risk patients with any of the following:
- Recurrent ischemia, despite meds- Recurrent ischemia, despite meds
- Elevated Troponin I or T- Elevated Troponin I or T
- New ST-segment depression- New ST-segment depression
- New CHF symptoms- New CHF symptoms
- High-risk stress test findings- High-risk stress test findings
- LV dysfunction (EF < 40%)- LV dysfunction (EF < 40%)
- Hemodynamic instability, sustained VT- Hemodynamic instability, sustained VT
- PCI within 6 months, prior CABG- PCI within 6 months, prior CABG
II IIaIIa IIbIIb IIIIII
Invasive Procedures 4Q 2006(among patients without contraindications to cath)
Invasive Procedures 4Q 2006(among patients without contraindications to cath)
Median TimesMedian Times
• Cath - 22 hrsCath - 22 hrs
• PCI - 21 hrsPCI - 21 hrs
• CABG - 69 hrsCABG - 69 hrs
83%
67%
53%
38%
12%
0%
20%
40%
60%
80%
100%
Cath Cath < 48 hr PCI PCI < 48 hr CABG
Management Strategies: 2007Early Invasive vs Selectively InvasiveEarly Invasive vs Selectively Invasive
Management Strategies: 2007Early Invasive vs Selectively InvasiveEarly Invasive vs Selectively Invasive
Early invasive: diagnostic angiography with intent to perform revascularization cath anticipated within 4-24 hours follows a foundation of risk-directed medical therapy
Selectively invasive (or early conservative): invasive evaluation only if optimal medical management fails
Note: from ED perspective, both strategies involve risk-directed, evidence-based medical therapy
Early invasive: diagnostic angiography with intent to perform revascularization cath anticipated within 4-24 hours follows a foundation of risk-directed medical therapy
Selectively invasive (or early conservative): invasive evaluation only if optimal medical management fails
Note: from ED perspective, both strategies involve risk-directed, evidence-based medical therapy
Management Strategies: 2007Early Invasive vs Selectively InvasiveEarly Invasive vs Selectively Invasive
Management Strategies: 2007Early Invasive vs Selectively InvasiveEarly Invasive vs Selectively Invasive
EIS is indicated in initially stabilized UA/NSTEMI patients (without contraindications) who have an elevated risk for clinical events
EIS is indicated in UA/NSTEMI patients (without contraindications) who have refractory angina or hemodynamic or electrical instability
SIS may be considered in initially stabilized patients who have an elevated risk for clinical events (including ↑Tn)
EIS is indicated in initially stabilized UA/NSTEMI patients (without contraindications) who have an elevated risk for clinical events
EIS is indicated in UA/NSTEMI patients (without contraindications) who have refractory angina or hemodynamic or electrical instability
SIS may be considered in initially stabilized patients who have an elevated risk for clinical events (including ↑Tn)
II IIaIIa IIbIIb IIIIII
Benefits of Early Catheterizationby Risk Group
Benefits of Early Catheterizationby Risk Group
0
2
4
6
8
10
12
Low Risk Moderate Risk High Risk
Early Cath No Early Cath
0
2
4
6
8
10
12
Low Risk Moderate Risk High Risk
Early Cath No Early Cath
- Bhatt AHA 2002- Bhatt AHA 2002
% I
nhos
pita
l Mor
talit
y%
Inh
ospi
tal M
orta
lity
Medical Management: 2007 GuidelinesMedical Management: 2007 GuidelinesAnti-Ischemic Therapy: Independent of StrategyAnti-Ischemic Therapy: Independent of Strategy
Medical Management: 2007 GuidelinesMedical Management: 2007 GuidelinesAnti-Ischemic Therapy: Independent of StrategyAnti-Ischemic Therapy: Independent of Strategy
NTG
Morphine
Beta-Blockers: emphasis on oral dosing
NTG
Morphine
Beta-Blockers: emphasis on oral dosing
IIII IIaIIaIIaIIa IIbIIbIIbIIb IIIIIIIIIIII
Medical Management: 2002 GuidelinesMedical Management: 2002 GuidelinesAnti-Thrombotic TherapyAnti-Thrombotic Therapy
Medical Management: 2002 GuidelinesMedical Management: 2002 GuidelinesAnti-Thrombotic TherapyAnti-Thrombotic Therapy
Immediate aspirin
Clopidogrel, if aspirin contraindicated
Heparin (IV unfractionated, LMW) with antiplatelet agents listed above
Enoxaparin preferred over UFH unless CABG is planned within 24 hours
Immediate aspirin
Clopidogrel, if aspirin contraindicated
Heparin (IV unfractionated, LMW) with antiplatelet agents listed above
Enoxaparin preferred over UFH unless CABG is planned within 24 hours
IIII IIaIIaIIaIIa IIbIIbIIbIIb IIIIIIIIIIII
Medical Management: 2007 GuidelinesMedical Management: 2007 GuidelinesAnti-Thrombotic TherapyAnti-Thrombotic Therapy
Medical Management: 2007 GuidelinesMedical Management: 2007 GuidelinesAnti-Thrombotic TherapyAnti-Thrombotic Therapy
In EIS:
enoxaparin or UFH
bivalirudin* or fondaparinux
In SIS:
enoxaparin or UFH
fondaparinux
In EIS:
enoxaparin or UFH
bivalirudin* or fondaparinux
In SIS:
enoxaparin or UFH
fondaparinux
IIII IIaIIaIIaIIa IIbIIbIIbIIb IIIIIIIIIIII
Immediate ASAImmediate ASA
Medical Management: 2007 GuidelinesMedical Management: 2007 GuidelinesAnti-Thrombotic TherapyAnti-Thrombotic Therapy
Medical Management: 2007 GuidelinesMedical Management: 2007 GuidelinesAnti-Thrombotic TherapyAnti-Thrombotic Therapy
Relevant new studies for antithrombotic therapy:
SYNERGY, JAMA 2004 10,027 patients with high-risk NSTE ACS, randomized
to enox vs UFH, open-label, superiority
OASIS-5, NEJM 2006 20,078 patients with high-risk NSTE ACS, randomized
to fonda vs enox, double-blind, noninferiority
ACUITY, NEJM 2006 13,819 patients with moderate or high-risk NSTE ACS,
randomized to hep/GPI vs bival/GPI vs bival, open-label, noninferiority
Relevant new studies for antithrombotic therapy:
SYNERGY, JAMA 2004 10,027 patients with high-risk NSTE ACS, randomized
to enox vs UFH, open-label, superiority
OASIS-5, NEJM 2006 20,078 patients with high-risk NSTE ACS, randomized
to fonda vs enox, double-blind, noninferiority
ACUITY, NEJM 2006 13,819 patients with moderate or high-risk NSTE ACS,
randomized to hep/GPI vs bival/GPI vs bival, open-label, noninferiority
Anti-Aggregation Antiplatelet Tx: 2002Anti-Aggregation Antiplatelet Tx: 2002Platelet GP IIb/IIIa InhibitorsPlatelet GP IIb/IIIa Inhibitors
Anti-Aggregation Antiplatelet Tx: 2002Anti-Aggregation Antiplatelet Tx: 2002Platelet GP IIb/IIIa InhibitorsPlatelet GP IIb/IIIa Inhibitors
Any GP IIb/IIIa inhibitor + ASA/Heparin for all patients, if cath/PCI planned
Eptifibatide or tirofiban + ASA/Heparin for high-risk* patients in whom early cath/PCI is not planned
Any GP IIb/IIIa inhibitor for patients already on ASA + Heparin + clopidogrel, if cath/PCI is planned
Any GP IIb/IIIa inhibitor + ASA/Heparin for all patients, if cath/PCI planned
Eptifibatide or tirofiban + ASA/Heparin for high-risk* patients in whom early cath/PCI is not planned
Any GP IIb/IIIa inhibitor for patients already on ASA + Heparin + clopidogrel, if cath/PCI is planned
II IIaIIa IIbIIb IIIIII
* High-risk: Age > 75; prolonged, ongoing CP; hemodynamic instability; rest CP w/ ST ; VT; positive cardiac markers * High-risk: Age > 75; prolonged, ongoing CP; hemodynamic instability; rest CP w/ ST ; VT; positive cardiac markers
Eptifibatide or tirofiban + ASA/Heparin for patients without continuing ischemia in whom PCI is not planned
Abciximab for patients in whom PCI is not planned
Eptifibatide or tirofiban + ASA/Heparin for patients without continuing ischemia in whom PCI is not planned
Abciximab for patients in whom PCI is not planned
II IIaIIa IIbIIb IIIIII
Ant-Aggregation Antiplatelet Tx: 2002Ant-Aggregation Antiplatelet Tx: 2002Platelet GP IIb/IIIa InhibitorsPlatelet GP IIb/IIIa Inhibitors
Ant-Aggregation Antiplatelet Tx: 2002Ant-Aggregation Antiplatelet Tx: 2002Platelet GP IIb/IIIa InhibitorsPlatelet GP IIb/IIIa Inhibitors
Anti-Activation Antiplatelet Therapy: 2002Anti-Activation Antiplatelet Therapy: 2002ClopidogrelClopidogrel
Anti-Activation Antiplatelet Therapy: 2002Anti-Activation Antiplatelet Therapy: 2002ClopidogrelClopidogrel
Aspirin + clopidogrel, for up to 1 month*
Aspirin + clopidogrel, for up to 9 months*
Withhold clopidogrel for 5-7 days for CABG
Aspirin + clopidogrel, for up to 1 month*
Aspirin + clopidogrel, for up to 9 months*
Withhold clopidogrel for 5-7 days for CABG
IIII IIaIIaIIaIIa IIbIIbIIbIIb IIIIIIIIIIII
* For patients managed with an early conservative strategy, and * For patients managed with an early conservative strategy, and those who are planned to undergo early PCIthose who are planned to undergo early PCI* For patients managed with an early conservative strategy, and * For patients managed with an early conservative strategy, and those who are planned to undergo early PCIthose who are planned to undergo early PCI
Guidelines do not specify initial timing of using Guidelines do not specify initial timing of using clopidogrel when coronary anatomy is unknownclopidogrel when coronary anatomy is unknownGuidelines do not specify initial timing of using Guidelines do not specify initial timing of using clopidogrel when coronary anatomy is unknownclopidogrel when coronary anatomy is unknown
Advanced Antiplatelet Tx: 2007Advanced Antiplatelet Tx: 2007Advanced Antiplatelet Tx: 2007Advanced Antiplatelet Tx: 2007
II IIaIIa IIbIIb IIIIII
All patients receive ASA
EIS: upstream clopidogrel or IIb/IIIa
EIS: upstream IIb/IIIa should be small-molecule
SIS: if medical management fails, add IIb/IIIa or clopidogrel . . .
. . . upstream
All patients receive ASA
EIS: upstream clopidogrel or IIb/IIIa
EIS: upstream IIb/IIIa should be small-molecule
SIS: if medical management fails, add IIb/IIIa or clopidogrel . . .
. . . upstream
Advanced Antiplatelet Tx: 2007Advanced Antiplatelet Tx: 2007Advanced Antiplatelet Tx: 2007Advanced Antiplatelet Tx: 2007
II IIaIIa IIbIIb IIIIII
SIS with recurrent ischemia on ASA, clopidogrel, and anticoag: add IIb/IIIa upstream
EIS: it is reasonable to give both clopidogrel and IIb/IIIa upstream
EIS: can omit IIb/IIIa if bivalirudin is anticoagulant + at least 300mg clopidogrel given > 6h prior to cath
SIS with recurrent ischemia on ASA, clopidogrel, and anticoag: add IIb/IIIa upstream
EIS: it is reasonable to give both clopidogrel and IIb/IIIa upstream
EIS: can omit IIb/IIIa if bivalirudin is anticoagulant + at least 300mg clopidogrel given > 6h prior to cath
Anti-Activation Antiplatelet Tx: 2007Anti-Activation Antiplatelet Tx: 2007More onMore on ClopidogrelClopidogrel
Anti-Activation Antiplatelet Tx: 2007Anti-Activation Antiplatelet Tx: 2007More onMore on ClopidogrelClopidogrel
II IIaIIa IIbIIb IIIIII
Clopidogrel with full loading dose in ASA-allergic patients
EIS: clopidogrel or IIb/IIIa administered upstream
SIS: clopidogrel initiated “as soon as possible” and continued for at least one month . . .
. . . and preferably for one year
Clopidogrel with full loading dose in ASA-allergic patients
EIS: clopidogrel or IIb/IIIa administered upstream
SIS: clopidogrel initiated “as soon as possible” and continued for at least one month . . .
. . . and preferably for one year
Antiplatelet Drug TargetsAntiplatelet Drug Targets
PlateletThrombin
ADP
Thromboxane A2
Epinephrine
Serotonin
Collagen
PAR-1
PAR-4
P2Y1
P2Y12
TXA2-R
5HT2A
Anionicphospholipidsurfaces
GP IIbGP IIbGP IIIaGP IIIa
GP VI
Platelet
GP IIIaGP IIIaGP IIbGP IIb
Fibrinogen
GP Ia
Clopidogrel Prasugrel
Aspirin
Gp IIb/IIIa inhibitors
P2Y12
00
22
44
66
88
1010
1212
1414
Dea
th, M
I, o
r S
tro
keD
eath
, MI,
or
Str
oke
Clopidogrel Clopidogrel + ASA+ ASA
33 66 99
Placebo Placebo + ASA+ ASA
Months of Follow-UpMonths of Follow-Up
11.4%11.4%
9.3%9.3%
20% RRR20% RRRPP < 0.001 < 0.001
N = 12,562N = 12,562
00 1212
N Engl J Med. 2001N Engl J Med. 2001
CURE Primary ResultsCURE Primary ResultsCURE Primary ResultsCURE Primary Results
%%%%
CURE: Ischemic Endpoints Were Reduced within 24h of Randomization
CURE: Ischemic Endpoints Were Reduced within 24h of Randomization
Adapted from Adapted from Yusuf S, et al. Yusuf S, et al. Circulation.Circulation. 2003;107:966-972. 2003;107:966-972.
Hours After RandomizationHours After Randomization
Cu
mu
lati
ve H
azar
d R
ates
Cu
mu
lati
ve H
azar
d R
ates
0.00.0
0.0050.005
0.0100.010
0.0150.015
0.0200.020
0.0250.025
00 22 44 66 88 1010 1212 1414 1616 1818 2020 2222 2424
RR = 0.67RR = 0.67P P = 0.003= 0.003
PlaceboPlacebo+ ASA+ ASA
ClopidogrelClopidogrel+ ASA+ ASA
33%33%RRRRRR
0 1 2
ACUITY Composite Ischemia at 1-YearACUITY Composite Ischemia at 1-Year
Hazard ratio±95% CI
Hazard ratio±95% CI
Bivalalone
UFH/Enox+ IIb/IIIa
HR (95% CI) Pint
0.67
Bivalirudin alone betterBivalirudin alone better UFH/Enox + IIb/IIIa betterUFH/Enox + IIb/IIIa better
19.8% 19.2% 1.09 (0.96-1.23)
21.1% 20.7% 1.04 (0.79-1.36)
9.0% 9.6% 0.97 (0.76-1.24)
Actual Treatment
PCI (n=5179)
CABG (n=1040)
Medical (n=2994)
17.7%
14.6%
16.4%
16.1%
1.14 (0.99-1.30)
0.95 (0.80-1.14)0.11
Biomarkers (CK/Trop)
Elevated (n=5072)
Normal (n=3402)
16.2%
16.4%
17.2%
14.3%
0.97 (0.86-1.11)
1.20 (1.01-1.44)0.07
Pre Thienopyridine
Yes (n=5751)
No (n=3305)
UFH/Enoxaparin + GPIIb/IIIa vs. Bivalirudin alone1 yr KM estimate
ACUITY 1-Year Data as presented at ACC 2007.
P value interaction
only between subgroups
Clopidogrel Dosing and Duration of TherapyClopidogrel Dosing and Duration of Therapy Clopidogrel Dosing and Duration of TherapyClopidogrel Dosing and Duration of Therapy
ordinarily given with ASA (established in CURE)
labeled loading dose 300mg Many cardiologists prefer 600mg for faster onset of
action, no apparent additional safety concerns
labeled maintenance dose 75mg Some cardiologists prefer 150mg for first month after
stenting
CURRENT (OASIS-7) trial currently studying 600 vs 300, 150 vs 75 (first month), and low- vs high-dose ASA
Results in 2009?
ordinarily given with ASA (established in CURE)
labeled loading dose 300mg Many cardiologists prefer 600mg for faster onset of
action, no apparent additional safety concerns
labeled maintenance dose 75mg Some cardiologists prefer 150mg for first month after
stenting
CURRENT (OASIS-7) trial currently studying 600 vs 300, 150 vs 75 (first month), and low- vs high-dose ASA
Results in 2009?
Clopidogrel Dosing and Duration of TherapyClopidogrel Dosing and Duration of Therapy Clopidogrel Dosing and Duration of TherapyClopidogrel Dosing and Duration of Therapy
duration of therapy after ACS, whether or nor PCI performed with BMS, with 75-162mg ASA
75mg daily for at least 1 month (I-A) preferably 12 months (I-B)
duration of therapy after ACS and PCI performed with DES, with 162-325mg ASA for at least 3 months after sirolimus-eluting stent and 6 months after paclitaxel-eluting stent . . . then indefinitely thereafter
75mg daily for at least 12 months (I-B)
CHARISMA showed no net benefit from long-term clopidogrel therapy to patients with cardiac risk factors but no objectively demonstrated CAD
duration of therapy after ACS, whether or nor PCI performed with BMS, with 75-162mg ASA
75mg daily for at least 1 month (I-A) preferably 12 months (I-B)
duration of therapy after ACS and PCI performed with DES, with 162-325mg ASA for at least 3 months after sirolimus-eluting stent and 6 months after paclitaxel-eluting stent . . . then indefinitely thereafter
75mg daily for at least 12 months (I-B)
CHARISMA showed no net benefit from long-term clopidogrel therapy to patients with cardiac risk factors but no objectively demonstrated CAD
Chest Pain or ACS Committee
Meets quarterly or PRN PRN means after . . .
• Pertinent, “practice-changing” new study published
• ACC / AHA / TCT meetings
• M & M or sentinel event
• New guidelines published
Chest Pain or ACS Committee
Meets quarterly or PRN PRN means after . . .
• Pertinent, “practice-changing” new study published
• ACC / AHA / TCT meetings
• M & M or sentinel event
• New guidelines published
Optimal Management of NSTE ACS: ED to Cardiology — A Functional Model
Chest Pain or ACS Committee comprised of: Emergency physicians Interventional cardiologists Medical cardiologists Hospitalists CT surgeons ED nursing Cath lab nursing CCU nursing Lab Imaging
Chest Pain or ACS Committee comprised of: Emergency physicians Interventional cardiologists Medical cardiologists Hospitalists CT surgeons ED nursing Cath lab nursing CCU nursing Lab Imaging
Optimal Management of NSTE ACS ED to Cardiology — A Functional Model
Chest Pain or ACS Committee discusses: Protocols and standing orders Practice variations versus evidence Time to catheterization predictability Reduction of medical errors in ACS care DTB times QI issues (CRUSADE / NRMI / ACTION) Transfers in, transfers out New data: How should it impact our protocols?
Chest Pain or ACS Committee discusses: Protocols and standing orders Practice variations versus evidence Time to catheterization predictability Reduction of medical errors in ACS care DTB times QI issues (CRUSADE / NRMI / ACTION) Transfers in, transfers out New data: How should it impact our protocols?
Optimal Management of NSTE ACS ED to Cardiology — A Functional Model
ED physicians should be using optimal, evidence-based, guideline-consistent medical therapy for NSTE ACS
ED physicians must work with their colleagues in cardiology to develop pathways and approaches (EDICT for ACS) for proper use of antithrombotic and antiplatelet therapy at all levels
ED physicians should facilitate early invasive management of ACS whenever feasible and appropriate
ED physicians should address issues related to bleeding risk as well as ischemic risk.
A seamless transition of care is most likely to result in good outcomes.
ED physicians should be using optimal, evidence-based, guideline-consistent medical therapy for NSTE ACS
ED physicians must work with their colleagues in cardiology to develop pathways and approaches (EDICT for ACS) for proper use of antithrombotic and antiplatelet therapy at all levels
ED physicians should facilitate early invasive management of ACS whenever feasible and appropriate
ED physicians should address issues related to bleeding risk as well as ischemic risk.
A seamless transition of care is most likely to result in good outcomes.
Optimal Management of NSTE ACS ED to Cardiology — Summary and Game Plan
We should be using optimal medical therapy for NSTE ACS in the ED, just as in the CCU or the cath lab.
There must be cross-disciplinary collaboration (EM, CD, IM, HM, CTS, nursing throughout all levels of care) to develop pathways for proper use of antithrombotic and antiplatelet therapy at all levels, to facilitate early invasive management whenever feasible, and to address issues related to bleeding risk as well as ischemic risk.
We should be using optimal medical therapy for NSTE ACS in the ED, just as in the CCU or the cath lab.
There must be cross-disciplinary collaboration (EM, CD, IM, HM, CTS, nursing throughout all levels of care) to develop pathways for proper use of antithrombotic and antiplatelet therapy at all levels, to facilitate early invasive management whenever feasible, and to address issues related to bleeding risk as well as ischemic risk.
Conclusion: NSTE ACSConclusion: NSTE ACS