stemi2007 focused update slideset
TRANSCRIPT
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ACC/AHA 2007 STEMI Guidelines Focused Update
ACC/AHA 2007 STEMI Guidelines
Focused Update Slide Set
Based on the 2007 Focused Update of theACC/AHA Guidelines for the Management of
Patients With ST-Elevation Myocardial
Infarction (STEMI): A Report of the ACC/AHA
Task Force on Practice Guidelines
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This slide set was adapted from the 2007Focused Update of theACC/AHA Guidelines for
Management of Patients With ST-ElevationMyocardial Infarction (Journal of the AmericanCollege of Cardiologypublished ahead of printon December 10, 2007, available athttp://content.onlinejacc.org/cgi/content/full/j.jacc.200
.
The full-text guidelines are also available on theWeb sites:
ACC (www.acc.org) and,AHA (www.americanheart.org)
http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001http://www.acc.org/http://www.americanheart.org/http://www.americanheart.org/http://www.acc.org/http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001 -
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Paul W. Armstrong, MD, FACC, FAHA
Eric R. Bates, MD, FACC, FAHA
Lee A. Green, MD, MPH
Lakshmi K. Halasyamani, MD
Judith S. Hochman, MD, FACC, FAHA
Harlan M. Krumholz, MD, FACC, FAHA
Elliott M. Antman, MD, FACC, FAHA,Co-Chair*
Mary Hand, MSPH, RN, FAHA, Co-Chair
Gervasio A. Lamas, MD, FACC
Charles J. Mullany, MB, MS, FACC
David L. Pearle, MD, FACC, FAHA
Michael A. Sloan, MD, FACC
Sidney C. Smith, Jr., MD, FACC, FAHA
*2004 Writing Committee Chair
Representing the Canadian Cardiovascular Society
Slide Set Editor
Elliott M. Antman, MD, FACC, FAHA
Special Thanks to
The 2007 STEMI Guidelines Focused Update Writing Committee Members
and
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Class IBenefit >>> Risk
Procedure/ TreatmentSHOULD be performed/administered
Class IIaBenefit >> Risk
Additional studies withfocused objectivesneeded
IT IS REASONABLE toperformprocedure/administertreatment
Class IIbBenefit Risk
Additional studies withbroad objectives needed;
Additional registry datawould be helpful
Procedure/TreatmentMAY BE CONSIDERED
Class IIIRisk BenefitNo additional studiesneeded
Procedure/Treatment
should NOT beperformed/administeredSINCE IT IS NOTHELPFUL AND MAY BEHARMFUL
shouldis recommendedis indicatedis useful/effective/ beneficial
is reasonablecan be useful/effective/
beneficialis probably recommended or
indicated
may/might be consideredmay/might be reasonableusefulness/effectiveness is
unknown /unclear/uncertain ornot well established
is not recommendedis not indicatedshould notis not
useful/effective/beneficialmay be harmful
Applying Classification of Recommendations
and Level of Evidence
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Class IBenefit >>> Risk
Procedure/ TreatmentSHOULD beperformed/administered
Class IIaBenefit >> Risk
Additional studies withfocused objectivesneeded
IT IS REASONABLE toperformprocedure/administertreatment
Class IIbBenefit Risk
Additional studies withbroad objectives needed;
Additional registry datawould be helpful
Procedure/TreatmentMAY BE CONSIDERED
Class IIIRisk BenefitNo additional studiesneeded
Procedure/Treatment
should NOT beperformed/administeredSINCE IT IS NOTHELPFUL AND MAY BEHARMFUL
Applying Classification of Recommendations
and Level of Evidence
Level A: Recommendation based on evidence from multiple randomized trials or meta-analyses Multiple(3-5) population risk strata evaluated; General consistency of direction and magnitude of effect
Level B: Recommendation based on evidence from a single randomized trial or non-randomized studiesLimited (2-3) population risk strata evaluated
Level C: Recommendation based on expert opinion, case studies, or standard-of-care Verylimited (1-2) population risk strata evaluated
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1990 1992 1994 1996 1998 2000 20021990
ACC/AHAAMI
R. Gunnar
1994AHCPR/NHLB
IUA
E. Braunwald
1996
1999 RevUpd
ACC/AHA AMIT. Ryan
20042007 RevUpd
ACC/AHASTEMI
2000 20022007
Rev UpdRev
ACC/AHA U
A/NSTEMIE. Braunwald J. Anderson
2004 2007
Evolution of Guidelines for ACS
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Hospitalizations in the U.S. Due to Acute
Coronary Syndromes (ACS)
Acute CoronarySyndromes*
1.57 Million Hospital Admissions - ACS
UA/NSTEMI STEMI
1.24 millionAdmissions per year
.33 millionAdmissions per year
Heart Disease and Stroke Statistics 2007 Update. Circulation 2007;115:69-171. *Primary and secondary diagnoses. About 0.57 million
NSTEMI and 0.67 million UA.
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Analgesia
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Analgesia
Morphine remains Class I for STEMIalthough may increase adverse eventsin UA/NSTEMI
NSAID medications increase mortality,reinfarction, and heart failure inproportion to degree of COX-2
selectivity Discontinue on admission for STEMI
Do not initiate during acute phase ofmanagement
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Patients routinely taking nonsteroidal anti-
inflammatory drugs (NSAIDs) (except for
aspirin), both non-selective as well as COX-2
selective agents, prior to STEMI should havethose agents discontinued at the time of
presentation with STEMI because of the
increased risks of mortality, reinfarction,
hypertension, heart failure, and myocardial
rupture associated with their use.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Analgesia
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NSAIDs (except for aspirin), both
nonselective as well as COX-2 selective
agents, should not be
administered during hospitalization forSTEMI
because of the increased risks of mortality,
reinfarction, hypertension, heart failure,
and
myocardial rupture associated with their
use.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Analgesia
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Beta-Blockers
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TREATMENT: Metoprolol 15 mg iv over 15 mins, then 200mg oral daily vs matching placebo
INCLUSION: Suspected acute MI (ST change or LBBB)within 24 h of symptom onset
EXCLUSION: Shock, systolic BP
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Effects of Metoprolol
Lancet. 2005;366:1622.
Death
13%
P=0.0006
ReMI
22%
P=0.0002
VF15%
P=0.002
Totality of Evidence (N = 52,411)COMMIT (N = 45,852)
Increased
early risk of
shock
Risk factors for cardiogenic shock :heart failure, age > 70 , systolic blood
pressure < 120, sinus tachycardia > 110 or heart rate < 60, increased timesince onset of STEMI symptoms
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Oral beta-blocker therapy should be initiated in thefirst 24 hours for patients who do not have any ofthe following: 1) signs of heart failure, 2) evidenceof a low output state, 3) increased risk* forcardiogenic shock, or 4) other relative
contraindications to beta blockade (PR interval >0.24 sec, 2nd - or 3rd-degree heart block, activeasthma, or reactive airway disease).
It is reasonable to administer an IV beta blocker at
the time of presentation to STEMI patients who arehypertensive and who do not have any of thefollowing: 1) signs of heart failure, 2) evidence of alow output state, 3) increased risk* for cardiogenicshock, or 4) other relative contraindications to betablockade (PR interval > 0.24 sec, 2nd - or 3rd-degree
heart block, active asthma, or reactive airway
Beta-Blockers
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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IV beta blockers should not beadministered to STEMI patients who haveany of the following: 1) signs of heartfailure, 2) evidence of a low output state,
3) increased risk* for cardiogenic shock,or 4) other relative contraindications tobeta blockade (PR interval > 0.24 sec,2nd - or 3rd-degree heart block, active
asthma, or reactive airway disease).
Beta-Blockers
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Primary PCI
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Primary PCI
STEMI patients presenting to a hospitalwith PCI capability should be treated withprimary PCI within 90 min of first medicalcontact as a systems goal.
STEMI patients presenting to a hospitalwithout PCI capability, and who cannot be
transferred to a PCI center and undergoPCI within 90 min of first medical contact,should be treated with fibrinolytic therapywithin 30 min of hospital presentation as asystems goal, unless fibrinolytic therapy is
contraindicated.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Options for Transport of Patients With
STEMI and Initial Reperfusion Treatment
EMS Transport
Onset of
symptoms ofSTEMI
9-1-1
EMSDispatch
EMS on-scene
Encourage 12-lead ECGs. Consider prehospital fibrinolytic if
capable and EMS-to-needle within
30 min.
GOALS
PCI
capable
Not PCI
capable
Hospital fibrinolysis:Door-to-Needle
within 30 min.
EMS
TriagePlan
Inter-
HospitalTransfer
Golden Hour = first 60 min. Total ischemic time: within 120 min.
Patient EMS Prehospital fibrinolysis
EMS-to-needlewithin 30 min.
EMS transport
EMS-to-balloon within 90 min.Patient self-transport
Hospital door-to-balloon
within 90 min.Dispatch
1 min.
5
min.8
min.
Antman EM, et al. J Am Coll Cardiol 2008. Published ahead of print on December 10, 2007. Available at
http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001. Figure 1.
http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001 -
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Facilitated PCI
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Meta-analysis: Facilitated PCI vs
Primary PCI
1.03
(0.15-7.13)
3.07
(0.18-52.0)
1.43
(1.01-2.02)
1.03(0.49-2.17)
Mortality Reinfarction Major Bleeding
Fac. PCI
Better
PPCI
Better
Fac. PCI
Better
PPCI
Better
Fac. PCI
Better
PPCI
Better
Keeley E, et al. Lancet2006;367:579.
0.1 1 10 0.1 1 10 0.1 1 10
1.38(1.01-1.87)
1.71(1.16 - 2.51)
1.51(1.10 - 2.08 )
Lytic alone
N=2953
IIb/IIIa alone
N=1148
Lytic +IIb/IIIaN=399
All(N=4500)
1.40
(0.49-3.98)
1.81
(1.19-2.77)
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A planned reperfusion strategy using full-dosefibrinolytic therapy followed by immediate PCIis not recommended and may be harmful.
Facilitated PCI using regimens other than full-dose fibrinolytic therapy might be consideredas a reperfusion strategy when all of thefollowing are present:
a. Patients are at high risk,b. PCI is not immediately available within 90minutes, andc. Bleeding risk is low (younger age, absence ofpoorly controlled hypertension, normal body
weight).
Facilitated PCI
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Facilitated PCI
Further Studies Ongoing
Prehospital fibrinolytic therapy Better anticoagulant and antiplatelettherapy Use in circumstances of longer delays toPCI
However, based on available data, facilitated PCIoffered no clinical benefit, and was associated withharm when full dose fibrinolytics were used.
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Rescue and Late PCI
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Wijeysundera HC, et al. J Am Coll Cardiol. 2007;49:422-430.
Meta-analysis: Rescue PCI vs Conservative Tx
Outcome Rescue PCI ConservativeTreatment
RR (95% CI) P
Mortality, %(n)
7.3(454)
10.4(457)
0.69(0.461.05)
.09
HF, %(n)
12.7(424)
17.8(427)
0.73(0.541.00)
.05
Reinfarction,
% (n)
6.1
(346)
10.7
(354)
0.58
(0.350.97)
.04
Stroke, % (n) 3.4(297)
0.7(295)
4.98(1.1022.48)
.04
Minor bleeding,% (n)
16.6(313)
3.6(307)
4.58(2.468.55)
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A strategy of coronary angiography withintent toperform PCI (or emergency CABG) isrecommended in patients who have receivedfibrinolytic therapy and have:
a. Cardiogenic shock in patients < 75 yearswho are suitable candidates for
revascularization
b. Severe congestive heart failure and/orpulmonary edema (Killip class III)
c. Hemodynamically compromising
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Rescue PCI
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Rescue PCI
A strategy of coronary angiography with
intent to
perform PCI (or emergency CABG) is
reasonable in patients 75 years whohave
received fibrinolytic therapy, and are in
cardiogenic shock, provided they are
suitablecandidates for revascularization.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Rescue PCI
A strategy of coronary angiography with
intent to perform rescue PCI is reasonable for
patients in whom fibrinolytic therapy has
failed (ST-segment elevation < 50% resolved
after 90 min following initiation of fibrinolytictherapy in the lead showing the worst initial
elevation) and a moderate or large area of
myocardium at risk [anterior MI, inferior MI
with right ventricular involvement orprecordial ST-segment depression].
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Rescue PCI
A strategy of coronary angiography with
intent to perform PCI in the absence of
any of the above Class I or IIa indications
might be reasonable in moderate- or
high-risk patients, but its benefits and
risks are not well established. The
benefits of rescue PCI are greater the
earlier it is initiated after the onset of
ischemic discomfort.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Rescue PCI
A strategy of coronary angiography with
intent to perform PCI (or emergency
CABG) is not recommended in patients
who have received fibrinolytic therapy if
further invasive management is
contraindicated or the patient or
designee do not wish further invasive
care.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Occluded Artery Trial (OAT)
Eligibility: Confirmed Index MI
Total IRA occlusion
3-28 days (>24 hours)
Exclusion criteria: Significant left main or 3 vessel
CAD
Hemodynamic or electrical
instability Rest or low-threshold angina
NYHA Class III-IV HF or shock
RESULTS2166 randomized1082 PCI + optimal medical therapy1084 Optimal medical therapy
(MED)
Death, MI, CHF Class IV4 year event rate:17.2% PCI vs 15.6% MEDHazard Ratio: PCI vs MED=1.16;95% Cl (0.92, 1.45); p=0.20
Fatal and Non fatal MI4 year event rate:7.0% PCI vs 5.3% MEDHazard Ratio: PCI vs MED=1.36;95% Cl (0.92, 2.00); p=0.13
Hochman JS, et al.Am Heart J2005;150:627-42;
Hochman JS, et al. N Engl J Med2006;355:2395-407.
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PCI of a hemodynamically significantstenosis in a patent infarct artery > 24hours after STEMI may be considered as
part of a invasive strategy.
PCI of a totally occluded infarct artery >24 hours after STEMI is not recommended
in asymptomatic patients with 1- or 2-vessel disease if they arehemodynamically and electrically stableand do not have evidence of severe
ischemia.
Late PCI after Fibrinolysis or for Patients Not
Undergoing Primary Reperfusion
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Anticoagulants
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Anticoagulants
Patients undergoing reperfusion withfibrinolytics should receive anticoagulanttherapy for a minimum of 48 hours (Level ofEvidence: C) and preferably for the duration ofthe index hospitalization, up to 8 days(regimens other than unfractionated heparin[UFH] are recommended if anticoagulanttherapy is given for more than 48 hoursbecause of the risk of heparin-induced
thrombocytopenia with prolonged UFHtreatment). (Level of Evidence: A)
Anticoagulant regimens with establishedefficacy include:
UFH (LOE: C)
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Anticoagulants
For patients undergoing PCI after havingreceived an anticoagulant regimen, the
followingdosing recommendations should be
followed:
a. For prior treatment with UFH: administeradditional boluses of UFH as needed to
support the procedure taking intoaccount whether GP IIb/IIIa receptorantagonists have been administered.(Level of Evidence: C) Bivalirudin mayalso be used in patients treated
previously with UFH. (Level of Evidence:
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Recommendation continues on the next slide.
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Anticoagulants
b. For prior treatment with enoxaparin: ifthe last SC dose was administered withinthe prior 8 hours, no additionalenoxaparin should be given; if the last
SC dose was administered at least 8 to12 hours earlier, an IV dose of 0.3 mg/kgof enoxaparin should be given.
c. For prior treatment with fondaparinux:administer additional intravenoustreatment with an anticoagulantpossessing anti-IIa activity taking intoaccount whether GP IIb/IIIa receptor
antagonists have been administered.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Anticoagulants
Because of the risk of catheter thrombosis,fondaparinux should not be used as thesoleanticoagulant to support PCI. An additional
anticoagulant with anti-IIa activity shouldbeadministered.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Unfractionated Heparin
Indirect thrombininhibitor so does notinhibit clot-boundthrombin
Nonspecific binding to: Serine proteases Endothelial cells
(can lead to variabilityin level ofanticoagulation)
Reduced effect in ACS Inhibited by PF-4
Causes plateletaggregation
Nonlinear
pharmacokinetics
Disadvantages Immediate
anticoagulation
Multiple sites of actionin coagulation cascade
Long history ofsuccessful clinical use
Readily monitored byaPTT and ACT
Advantages
Hirsh J, et al. Circulation. 2001;103:2994-3018. aPTT = activated partial thromboplastin time; ACT = activated coagulation time; PF-4 =
platelet factor 4; HIT = heparin-induced thrombocytopenia.
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ExTRACT-TIMI 25: Primary End Point (ITT)
Death or Nonfatal MI
0
3
6
9
12
15
0 5 10 15 20 25 30
Prima
ryEn
dPo
int
(%) Enoxaparin
UFH
Relative Risk0.83 (95% CI, 0.77 to
0.90)
P
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Low-Molecular-Weight Heparin
Indirect thrombin inhibitor
Less reversible
Difficult to monitor(no aPTT or ACT)
Renally cleared
Long half-life Risk of HIT
Disadvantages Increased anti-Xa to anti-IIa
activity inhibits thrombingeneration more effectively
Induces release of TFPI vsUFH
Not neutralized by platelet
factor 4 Less binding to plasma
proteins (eg, acute-phasereactant proteins) moreconsistent anticoagulation
Lower rate of HIT vs UFH
Lower fibrinogen levels Easy to administer (SC
administration)
Long history of clinicalstudies and experience, FDA-approved indications
Monitoring typicallyunnecessary
Advantages
Hirsh J, et al. Circulation. 2001;103:2994-3018. TFPI = tissue factor pathway inhibitor; UFH = unfractionated heparin;
SC = subcutaneous; aPTT = activated partial thromboplastin time;
ACT = activated coagulation time.
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OASIS-6 Trial: Results
15%
Primary End Point:
Death/Reinfarction (%)
P=.008 P=.003 P=.008
Frequenc y
12%
9%
6%
3%
0%
9.7%
11.2%
7.4%
8.9%
13.4%
14.8%
30 days 9 days 3-6 months
Fondaparinux (n=6036) Control (n=6056)
14%
Reduction in Death/MI at 30 days:
Stratum 1 (No UFH indicated)
P
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Fondaparinux
Difficult to monitor (noaPTT or ACT)
Long half-life
Catheter thrombosisduring PCI
DisadvantagesAdvantages
SC administration Potential exists for
outpatientmanagement
Once-daily
administration Predictable
anticoagulant response Fixed dose No antigenicity Potentially no need for
serologic parameters Does not cross the
placenta HIT antibodies do not
cross-react Decreased bleeding
complications vs UFH orSimoons ML, et al. J Am Coll Cardiol. 2004;43:2183-2190.
Yusuf S, et al. N Engl J Med. 2066;354:1464-1476.
Summary of Observations from Trials of Anticoagulants for STEMI
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Anticoagulant
Efficacy (through 30 d) Safety Use During PCI
Reviparin Fibrinolysis: probably superior
to placebo.*
No reperfusion: probably superior toplacebo.*
risk of seriousbleeds
No data on reviparin aloneduring PCI. Additional
anticoagulant with anti-IIaactivity, such as UFH orbivalirudin, recommended.
Fondaparinux Fibrinolysis: appears superior to controlrx (placebo/UFH). Relative benefit vsplacebo and UFH separately cannot bereliably determined from availabledata.*
Primary PCI: when used alone, noadvantage over UFH and trend towardworse outcome.
No reperfusion: appears superior tocontrol therapy (placebo/UFH). Relativebenefit versus placebo and UFHseparately cannot be reliablydetermined from available data.*
Trend toward riskof serious bleeds
risk of catheter thrombosiswhen fondaparinux used alone.Additional anticoagulant withanti-IIa activity, such as UFH orbivalirudin, recommended.
Enoxaparin Fibrinolysis: appears superior to UFH risk of seriousbleeds
Enoxaparin can be used tosupport PCI after fibrinolysis.No additional anticoagulantneeded.
Summary of Observations from Trials of Anticoagulants for STEMI
Antman EM, et al. J Am Coll Cardiol 2008. Published ahead of print on December 10, 2007. Available at
http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001.Table 10.
http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001http://content.onlinejacc.org/cgi/content/full/j.jacc.2007.10.001 -
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Thienopyridines
CLARITY TIMI 28 Primary Endpoint:
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CLARITY-TIMI 28 Primary Endpoint:Occluded Artery (or D/MI thru Angio/HD)
PlaceboClopidogrelLD 300 mgMD 75 mg
P=0.00000036P=0.00000036
Odds Ratio 0.64
(95% CI 0.53-0.76)
Odds Ratio 0.64
(95% CI 0.53-0.76)
Clopidogrelbetter
Placebobetter
n=1752 n=1739
Sabatine N Eng J Med2005;352:1179.
STEMI, Age 18-75
15.0
21.7
0
5
10
15
20
25
Occ
lud
edArte
ryorDeath/M
I(%)
1.00.4 0.6 0.8 1.2 1.6
36%Odds
Reduction
36%Odds
Reduction
COMMIT: Effect of CLOPIDOGREL on
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Dead
(%)
Days Since Randomization (up to 28 days)
Placebo + ASA:
1,846 deaths (8.1%)Clopidogrel + ASA:
1,728 deaths (7.5%)
0.6% ARD
7% RRR
P= 0.03
N = 45,852
No Age limit ; 26% > 70 y
Lytic Rx 50%
No LD given
COMMIT: Effect of CLOPIDOGREL on
Death In Hospital
Chen ZM, et al. Lancet. 2005;366:1607.
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Clopidogrel 75 mg per day orally should be
added to aspirin in patients with STEMI
regardless of whether they undergo
reperfusion with fibrinolytic therapy or do
not receive reperfusion therapy.
Treatment with clopidogrel should continue
for at least 14 days.
Thienopyridines
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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In patients < 75 years who receivefibrinolytic therapy or who do not receivereperfusion therapy, it is reasonable toadminister an oral clopidogrel loading doseof 300 mg. (No data are available to guidedecision making regarding an oral loadingdose in patients 75 years of age.)
Long-term maintenance therapy (e.g., 1
year) with clopidogrel (75 mg per dayorally) can be useful in STEMI patientsregardless of whether they undergoreperfusion with fibrinolytic therapy or do
not receive reperfusion therapy.
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
Thienopyridines
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Hospital Care
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It is reasonable for patients with STEMI who
do not undergo reperfusion therapy to be
treated with anticoagulant therapy (non-
UFH regimen) for the duration of the index
hospitalization, up to 8 days.
Convenient strategies that can be used
include those with LMWH (Level of
Evidence: C) or fondaparinux (Level of
Evidence: B) using the same dosing
regimens as for patients who receive
fibrinolytic therapy.
Anticoagulants
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Coronary arteriography may be consideredas part of an invasive strategy for riskassessment after fibrinolytic therapy (Levelof Evidence: B) or for patients not
undergoing primary reperfusion. (Level ofEvidence: C)
Invasive Evaluation
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
III IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIII IIaIIaIIa IIbIIbIIb IIIIIIIIIIIaIIaIIa IIbIIbIIb IIIIIIIII
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Secondary Prevention and
Long-Term Management
S d P ti
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Secondary Prevention
Ask, advise, assess, and assist patients tostop smoking I (B)
Clopidogrel 75 mg daily: PCI I (B)
no PCI IIa (C) Statin goal:
LDL-C < 100 mg/dL I (A) consider LDL-C < 70 mg/dL IIa (A)
Daily physical activity 30 min 7 d/wk,minimum 5 d/wk I (B) Annual influenza immunization I (B)
Secondary Prevention and Long Term Management
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Secondary Prevention and Long Term Management
Status of tobacco use should be asked at
every visit.Every tobacco user and family memberwho smoke should be advised to quit atevery visit.
The tobacco users willingness to quit
should be assessed.The tobacco user should be assisted bycounseling and developing a plan forquitting.
Follow-up, referral to special programs,or pharmacotherapy (including nicotinereplacement and pharmacological rx)should be arranged.
Exposure to environmental tobacco
smoke at home and work should beavoided.
Smoking
2007Goal:Complete
cessation.
No exposure toenvironmental
tobacco smoke.
Goals Class I Recommendations
NEW
NEW
Secondary Prevention and Long Term Management
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If blood pressure is 140/90 mm Hg or 130/80 mm Hg for patients withchronic kidney disease or diabetes:
It is recommended to initiate or maintain
lifestyle modification (weight control, physical activity, alcohol moderation, sodium, and emphasis on consumption of freshfruits, vegetables, and low-fat dairyproducts).
It is useful as tolerated, to add bloodpressure medication, treating initially withbeta-blockers and/or ACE inhibitors, with theaddition of other drugs such as thiazides as
needed to achieve goal BP.
Bloodpressure
control:2007Goal:
< 140/90 mm
Hg or
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Starting dietary therapy in all patients is
recommended. intake of sat. fats (< 7% oftotal calories), trans fatty acids and cholesterol(< 200 mg/d).
Adding plant stanol/sterols (2 g/d) and/or
viscous fiber (> 10 g/d) is reasonable to furtherlower LDL-C. (Class IIa; LOE:A)
Promotion of daily physical activity and weightmanagement is recommended.
It may be reasonable to encourage consumption of omega-3 fatty acids in the formof fish or in capsule form (1 g/d) for riskreduction. For treatment of elevated TG, higherdoses are usually necessary for risk reduction.
(Class IIb; LOE: B)
Lipidmanagement:2007 goal:LDL-C
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A fasting lipid profile should be assessed in all
patients and within 24 hours of hospitalization forthose with an acute cardiovascular or coronaryevent. For hospitalized patients, initiation of lipid-lowering medication is indicated as recommendedbelow before discharge according to the followingschedule:
LDL-C should be < 100 mg/dL. Further reduction to < 70 mg /dL is reasonable.
(Class IIa; LOE: A) If baseline LDL-C is 100 mg/dL, LDL-lowering
drug rx should be initiated. If on-treatment LDL-C is 100 mg/dLintensify LDL-lowering drug rx (may require LDL-lowering combination is recommended.
If baseline LDL-C is 70 to 100 mg/dL, it isreasonable to treat to LDL-C < 70 mg/dL. (Class
IIa; LOE: B)
Lipidmanagement:2007 goal:LDL-C
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If TG are 150 mg per dL or HDL-C < 40 mg per dL,
weight management, physical activity, and smoking cessationshould be emphasized.
If TGs are 200 to 499 mg per dL, nonHDL-C target should beless than 130 mg per dL.
If TGs are 200 to 499 mg/dL, nonHDL-C target is < 130
mg/dL. (Class I; LOE: B); further reduction of nonHDL-C to