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Acute Coronary Syndrome

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Title: Acute Coronary Syndrome


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Acute Coronary Syndrome
  • Dr. S.A. moezzi

3
ACS Overview
  • Overview of ACS
  • Assessment of Likelihood of ACS
  • Early Risk Stratification
  • Invasive vs Conservative Strategy
  • Pharmacotherapy
  • Long-term Therapy/Secondary Prevention

4
Scope of the Problem
  • 5 million ER visits nationwide for CP
  • 800,000 experience an MI each year
  • 213,000 die from their event
  • ½ of those die before reaching the ER
  • Pre-CCU, mortality for MI was gt30
  • Fell to 15 with CCU
  • With current interventions, in hospital mortality
    of STEMI is 6-7

5
Overview of ACS
Acute Coronary Syndromes
1.57 Million Hospital Admissions - ACS
UA/NSTEMI
STEMI
1.24 million Admissions per year
0.33 million Admissions per year
Primary and secondary diagnoses. About 0.57
million NSTEMI and 0.67 million UA. Heart Disease
and Stroke Statistics 2007 Update. Circulation
2007 11569171.
6
Acute Coronary Syndrome (ACS)
  • Definition The spectrum of acute ischemia
    related syndromes ranging from UA to MI with or
    without ST elevation that are secondary to acute
    plaque rupture or plaque erosion.
  • ----UA---------NSTEMI----------STEMI----

7
Pathophysiology of Stable Angina and ACS
Pathophysiology
ACS
  • Decreased O2 Supply
  • Flow- limiting stenosis
  • Anemia
  • Plaque rupture/clot
  • Increased O2 Demand

Asymptomatic
Angina
Myocardial Infarction
O2 supply/demand mismatch?Ischemia
Myocardial ischemia?necrosis
8
Pathophysiology of ACSEvolution of Coronary
Thrombosis
9
  • Unstable Angina

NSTEMI
  • STEMI

Non-occlusive thrombus sufficient to cause
tissue damage mild myocardial necrosis ST
depression /- T wave inversion on
ECG Elevated cardiac enzymes
Non occlusive thrombus Non specific
ECG Normal cardiac enzymes
Complete thrombus occlusion ST elevations on
ECG or new LBBB Elevated cardiac enzymes More
severe symptoms
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STEMI
  • Name 3 situations in which you cannot diagnose
    STEMI

11
STEMI
  • Name 3 situations in which you cannot diagnose
    STEMI
  • Left Ventricular Hypertrophy
  • Chronic or Rate Dependent LBBB
  • Paced Rhythm

12
Diagnosis of ACS
  • At least 2 of the following
  • History ( angina or angina equivalent)
  • Acute ischemic ECG changes
  • Typical rise and fall of cardiac markers
  • Absence of another identifiable etiology

13
Likelihood of ACS by Hx/PE
  • Suggesting AMI
  • LR 2.7
  • LR 2.9 (1.4-6.0)
  • LR 2.3 (1.7-3.1)
  • LR 7.1 (3.6-14.2)
  • LR 2.0 (1.9-2.2)
  • LR 3.2 (1.6-6.5)
  • LR 3.1 (1.8-5.2)
  • LR 2.1 (1.4-3.1)
  • History/Examination
  • Pain in Chest or Left Arm
  • CP Radiation
  • Right Shoulder
  • Left Arm
  • Both Left Right Arm
  • Diaphoresis
  • 3rd Heart Sound
  • SBP lt 80 mm Hg
  • Pulmonary Crackles
  • Panju AA.
    JAMA. 19982801256.

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Likelihood of ACS by Hx/PE
Against AMI LR 0.2 (0.2-0.3) LR 0.3 (0.2-0.5) LR
0.3 (0.2-0.4) LR 0.2-0.4
  • Clinical Examination
  • Pleuritic Chest Pain
  • Sharp or Stabbing Pain
  • Positional Chest Pain
  • Reproducible Chest Pain
  • Panju AA. JAMA.
    19982801256.

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Risk Stratification by ECG
  • Simple, quick, noninvasive tool
  • Universally available, cheap
  • Correlates with risk and prognosis
  • Guides treatment decisions
  • Can identify alternative causes

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Risk Stratification by ECG
  • ECG Findings and Associated LR for AMI
  • New ST-E gt 1mm LR 5.7-53.9
  • New Q waves LR 5.3-24.8
  • Any ST-E LR 11.2 (7.1-17.8)
  • New Conduction Defect LR 6.3 ( 2.5-15.7)
  • New ST-D LR 3.0-5.2
  • NORMAL ECG LR 0.1-0.4
  • Panju AA. JAMA. 19982801256.

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Risk Stratification by ECG
  • 1-8 AMI have a normal ECG
  • Only Approx 50 of AMI patients have diagnostic
    changes on their initial ECG
  • Peter J. Zimetbaum, M.D., N Engl J Med
    2003348933-40.

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Risk Stratification by ECG
  • 1 ECG cannot exclude AMI
  • Brief sample of a dynamic process
  • Small regions of ischemia or infarction may be
    missed
  • Peter J. Zimetbaum, M.D., N Engl J Med
    2003348933-40.

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How Sensitive is the ECG Alone?
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How Predictive is NTG response?
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Timing of Release of Various Biomarkers After
Acute Myocardial Infarction
Shapiro BP, Jaffe AS. Cardiac biomarkers. In
Murphy JG, Lloyd MA, editors. Mayo Clinic
Cardiology Concise Textbook. 3rd ed. Rochester,
MN Mayo Clinic Scientific Press and New York
Informa Healthcare USA, 200777380. Anderson
JL, et al. J Am Coll Cardiol 200750e1e157,
Figure 5.
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Risk Stratification by Troponin
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National Academy of Clinical Biochemistry
Laboratory Medicine (NACB) and the Joint
ESC/ACCF/AHA/WHF Task Force for the Redefinition
of Myocardial Infarction
  •   Cardiac troponin is the preferred marker for
    the diagnosis of MI and for risk stratification.
    CK-MB by mass assay is an acceptable alternative
    when troponin in not available.
  •   CK-MB was preferred by the NACB for the
    detection of reinfarction early after the index
    event
  • increased sensitivity and specificity of cTn
    should make it the marker of choice it is
    unnecessary to obtain both values.
  • Cardiac troponins I and T are equally useful.

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Non ACS causes of Troponin Elevation
  1. Trauma (including contusion ablation pacing
    ICD firings,, endomyocardial biopsy, cardiac
    surgery, after-interventional closure of ASDs)
  2. Congestive heart failure (acute and chronic)
  3. Aortic valve disease and HOCM with significant
    LVH
  4. Hypertension
  5. Hypotension, often with arrhythmias
  6. Noncardiac surgery
  7. Renal failure
  8. Critically ill patients, especially with
    diabetes, respiratory failure
  9. Drug toxicity (eg, adriamycin, 5 FU, herceptin,
    snake venoms)
  10. Hypothyroidism
  11. Coronary vasospasm, including apical ballooning
    syndrome
  12. Inflammatory diseases (eg, myocarditis, Kawasaki
    disease, smallpox vaccination,
  13. Post-PCI
  14. Pulmonary embolism, severe pulmonary hypertension
  15. Sepsis
  16. Burns, especially if TBSA greater than 30
  17. Infiltrative diseases amyloidosis,
    hemachromatosis, sarcoidosis, and scleroderma
  18. Acute neurologic disease, including CVA,
    subarchnoid bleeds
  19. Rhabdomyolysis with cardiac injury

Modified from Apple FS, et al Heart J.
2002144981-986.
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Combined Sensitivities for ACS
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Unstable angina/NSTEMI cardiac care
  • Evaluate for conservative vs. invasive strategy
    based upon
  • Likelihood of actual ACS
  • Risk stratification by TIMI risk score
  • ACS risk categories per AHA guidelines

Low
High
Intermediate
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  • TIMI Risk Score
  • Predicts risk of death, new/recurrent MI, need
    for urgent revascularization within 14 days

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TIMI Risk Score
T Troponin elevation (or CK-MB elevation) H
History or CAD (gt50 Stenosis) R Risk Factors
gt 3 (HTN, Hyperlipidemia, Family Hx, DM II,
Active Smoker)
E EKG changes ST elevation or depression 0.5
mm concordant leads A2Aspirin use within the
past 7 days Age over 65 T Two or more
episodes of CP within 24 hours
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Deciding between Early Invasive vs a Conservative
Strategies
  • Hemodynamic instability
  • Elecrical instability
  • Refractory angina
  • PCI in past 6 months
  • CABG
  • EF lt40

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Specifics of Early Hospital Care
  • Anti-Ischemic Therapy
  • Anti-Platelet Therapy
  • Anticoagulant Therapy

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Early Hospital CareAnti-Ischemic Therapy
  • Class I
  • Bed/Chair rest and Telemetry
  • Oxygen (maintain saturation gt90)
  • Nitrates (SLx3 Oral/topical. IV for ongoing
    iscemia, heart failure, hypertension)
  • Oral B-blockers in First 24-hours if no
    contraindications. (IV B-blockers class IIa
    indication)
  • Non-dihydropyridine Ca-channel blockers for those
    with contraindication fo B-blockers
  • ACE inhibitors in first 24-hours for heart
    failure or EFlt40 (Class IIa for all other pts)
    (ARBs for those intolerant)
  • Statins

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Early Hospital CareAnti-Ischemic Therapy
  • Class III
  • Nitrates if BPlt90 mmHg or RV infarction
  • Nitrates within 24-hrs of Sildenafil or 48 hrs of
    Tadalafil
  • Immediate release dihydropyradine Ca-blockers in
    the absence of B-Blocker therapy
  • IV ACE-inhibitors
  • IV B-blockers in patients with acute HF, Low
    output state or cardiogenic shock, PR interval
    gt0.24 sec, 2nd or 3rd degree heart block, active
    asthma, or reactive airway disease
  • NSAIDS and Cox-2 inhibitors

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Early Hospital CareAnti-Platelet Therapy
  • Class I
  • Aspirin (162-325 mg), non enteric coated
  • Clopidogrel for those with Aspirin
    allergy/intolerance (300-600 mg load and 75 mg/d)
  • GI prophylaxis if a Hx of GI bleed
  • GP IIb/IIIa inhibitors should be evaluated based
    on whether an invasive or conservative strategy
    is used
  • GP IIb/IIIa inhibitors recommended for all
    diabetics and all patient in early invasive arm

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secondary prevention
  • At present, the United States Food and Drug
    Administration recommends daily doses of 75 to
    325 mg,
  • the 2006 American College of Cardiology /American
    Heart Association (ACC/AHA) guidelines on
    recommends daily doses of 75 to 162 mg for
    secondary prevention 38.
  • The ACCP recommends a daily dose of 75 to 100 mg

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Early Hospital CareAnticoagulant Therapy
  • Class I
  • Unfractionated Heparin
  • Enoxaparin
  • Bivalarudin
  • Fondaparinux
  • Relative choice depends on invasive vs
    conservative strategy and bleeding risk

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Early Hospital CareStatin Therapy
  • MIRACL TrialInclusion Criteria
  • 3086 patients with Non ST ACS
  • Total cholesterol lt270 mg/dl
  • No planned PCI
  • Randomized to Atorvastatin vs Placebo
  • Drug started at 24-96 hours

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Statin Evidence MIRACL Study
Primary Efficacy Measure
Placebo
17.4
15
14.8
Atorvastatin
10
  • Time to first occurrence of
  • Death (any cause)
  • Nonfatal MI
  • Resuscitated cardiac arrest
  • Worsening angina with new objective evidence and
    urgent rehospitalization

Cumulative Incidence ()
5
Relative risk 0.84P .048 95 CI 0.701-0.999
0
0
4
8
12
16
Time Since Randomization (weeks)
Schwartz GG, et al. JAMA. 20012851711-1718.
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Statin Evidence MIRACL Study
Fatal and Nonfatal Stroke
Waters DD, et al. Circulation. 20021061690-1695.
S24
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PROVE-IT Trial
All-Cause Death or Major CV Events in All
Randomized Subjects
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Pravastatin 40mg (26.3)
25
20
with Event
Atorvastatin 80mg (22.4)
15
10
16 RR (P 0.005)
5
0
Months of Follow-up
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Summary of PROVE-IT Results
  • In patients recently hospitalized within 10 days
    for an acute coronary syndrome
  • Intensive high-dose LDL-C lowering (median
    LDL-C 62 mg/dL) compared to moderate
    standard-dose lipid-lowering therapy (median
    LDL-C 95 mg/dL) reduced the risk of all cause
    mortality or major cardiac events by 16
    (p0.005)
  • Benefits emerged within 30 days post ACS with
    continued benefit observed throughout the 2.5
    years of follow-up
  • Benefits were consistent across all
    cardiovascular endpoints, except stroke, and most
    clinical subgroups

44
Invasive vs Conservative Strategies
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Invasive vs Conservative Strategy Clinical Trials
ISAR-COOL
ICTUS (05)
RITA-3 (02)
VANQWISH (98)
VINO
MATE
TRUCS
TIMI IIIB (94)
TACTICS-TIMI 18 (01)
FRISC II (99)
Weight of the evidence
ConservativeStrategy Favored N920
InvasiveStrategy Favored N7,018
No difference N2,874
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How Early is Early?
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Secondary PreventionClass I Indications
  • Aspirin
  • Beta-blockers (all pts, slow titration with
    moderate to severe failure
  • ACE-Inhibitors CHF, EFlt40, HTN, DM
  • (All pts-Class IIa) ARB when intolerant to
    ACE. (Class IIa as alternative to ACEI)
  • Aldosterone blockade An ACEI, CHF with either
    EFlt40 or DM and if CrClgt30 ml/min and Klt5.0
    mEq/L
  • Statins
  • Standard Risk Factor Management

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Long-Term Antithrombotic Therapy at Hospital
Discharge after UA/NSTEMI
UA/NSTEMI Patient Groups at Discharge
Medical Therapy without Stent
Bare Metal Stent Group
Drug Eluting Stent Group
ASA 162 to 325 mg/d for at least 3 to 6 months,
then 75 to 162 mg/d indefinitely (Class I, LOE
A) Clopidogrel 75 mg/d for at least 1 year
(Class I, LOE B)
ASA 162 to 325 mg/d for at least 1 month, then 75
to 162 mg/d indefinitely (Class I, LOE A)
Clopidogrel 75 mg/d for at least 1 month and
up to 1 year (Class I, LOEB)
ASA 75 to 162 mg/d indefinitely (Class I, LOE A)
Clopidogrel 75 mg/d at least 1 month (Class
I, LOE A) and up to 1 year (Class I, LOE B)
Indication for Anticoagulation?
Yes
No
Add Warfarin (INR 2.0 to 2.5) (Class IIb, LOE B)
Continue with dual antiplatelet therapy as above
Anderson JL, et al. J Am Coll Cardiol
200750e1e157, Figure 11. INR international
normalized ratio LOE level of evidence.
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Secondary PreventionClass III
  • Hormone Replacement Therapy
  • Antioxidants (Vit C, Vit E)
  • Folic Acid

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Early Treatment with Clopidogrel
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Shortcomings of the CURE Trial
  • Conducted primarily at centers without routine
    use of early invasive strategy
  • Only 462 (3.7) patients enrolled from the U.S.
  • 44 had catheterization during index
    hospitalization
  • Adverse event reduced only in nonfatal MI set
  • Major Bleeding rate of 9.6 among patients who
    were administered clopidogrel within 5 days of
    CABG

53
ClopidogrelBleeding Risk and CABG
  • In hospitals in which patients with UA/NSTEMI
    undergo rapid diagnostic catheterization within
    24 hours of admission, clopidogrel is not started
    until it is clear that CABG will not be scheduled
    within the next several days. However, unstable
    patients should receive clopidogrel or be take
    for immediate angiography.

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Clopidogrel vs. Prasugrel
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Prasugrel-Key Facts
  • Contraindicated in pts with prior TIA/Stroke
  • Not recommended for patients gt75 years
  • 5 mg maintenance dose suggested in patients lt60
    Kg, though this dose has not been studied

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Summary
  • ACS includes UA, NSTEMI, and STEMI
  • Management guideline focus
  • Immediate assessment/intervention (MONABAH)
  • Risk stratification (UA/NSTEMI vs. STEMI)
  • RAPID reperfusion for STEMI (PCI vs.
    Thrombolytics)
  • Conservative vs Invasive therapy for UA/NSTEMI
  • Aggressive attention to secondary prevention
    initiatives for ACS patients
  • Beta blocker, ASA, ACE-I, Statin

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Ten Points to Remember from the 2009 STEMI
Guideline Update
  • Antman EM, Hand M,
  • Armstrong PW, et al.,

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Ten Points to Remember from the 2009 STEMI
Guideline Update
  1. Patients routinely taking NSAIDs (except for
    aspirin), both nonselective as well as COX-2
    selective agents, before STEMI should have those
    agents discontinued at the time of presentation
    with STEMI because of the increased risk of
    mortality, reinfarction, hypertension, heart
    failure, and myocardial rupture associated with
    their use.

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Ten Points to Remember from the 2009 STEMI
Guideline Update
  • Oral beta-blocker therapy should be initiated in
    the first 24 hours for patients who do not have
    any of the following
  • Signs of heart failure
  • Evidence of a low output state
  • Increased risk for cardiogenic shock
  • Other relative contraindications to beta blockade
  • PR interval gt 0.24 seconds
  • Second- or third-degree heart block
  • Active asthma or reactive airway disease

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Ten Points to Remember from the 2009 STEMI
Guideline Update
  1. STEMI patients presenting to a hospital with PCI
    capability should be treated with primary PCI
    within 90 minutes of first medical contact as a
    systems goal.
  2. STEMI patients presenting to a hospital without
    PCI capability and who cannot be transferred to a
    PCI center and undergo PCI within 90 minutes of
    first medical contact should be treated with
    fibrinolytic therapy within 30 minutes of
    hospital presentation as a systems goal unless
    fibrinolytic therapy is contraindicated.

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Ten Points to Remember from the 2009 STEMI
Guideline Update
  • A strategy of coronary angiography with intent to
    perform PCI (or emergency CABG) is recommended
    for patients who have received fibrinolytic
    therapy and have any of the following
  • Cardiogenic shock in patients lt75 years who are
    suitable candidates for revascularization,
  • Severe congestive heart failure and/or pulmonary
    edema (Killip class III), or
  • Hemodynamically compromising ventricular
    arrhythmias

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Ten Points to Remember from the 2009 STEMI
Guideline Update
  1. Patients undergoing reperfusion with
    fibrinolytics should receive anticoagulant
    therapy for a minimum of 48 hours and preferably
    for the duration of the index hospitalization, up
    to 8 days (regimens other than unfractionated
    heparin UFH are recommended if anticoagulant
    therapy is given for more than 48 hours because
    of the risk of heparin- induced thrombocytopenia
    with prolonged UFH treatment).

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Ten Points to Remember from the 2009 STEMI
Guideline Update
  1. 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.
  2. Every tobacco user and family members who smoke
    should be advised to quit at every visit.

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Ten Points to Remember from the 2007 STEMI
Guideline Update
  • 9. For all post-PCI STEMI stented patients
    without aspirin resistance, allergy, or increased
    risk of bleeding, aspirin at a dose of 162-325 mg
    daily should be given for at least 1 month after
    bare-metal stent (BMS) implantation, 3 months
    after sirolimus-eluting stent implantation, and 6
    months after paclitaxel-eluting stent
    implantation, after which long-term aspirin use
    should be continued indefinitely at a dose of
    75-162 mg daily.

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Ten Points to Remember from the 2007 STEMI
Guideline Update
  1. For all post-PCI patients who receive a
    drug-eluting stent, clopidogrel 75 mg daily
    should be given for at least 12 months if
    patients are not at high risk of bleeding. For
    post-PCI patients receiving a BMS, clopidogrel
    should be given for a minimum of 1 month and
    ideally up to 12 months (unless the patient is at
    increased risk of bleeding then it should be
    given for a minimum of 2 weeks).

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ACC/AHA Guideline Classification System Level of
Evidence (LOE)
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Beta-blockers in STEMI
  • Class I - oral beta-blockers should be initiated
    within 24 hours LOE B
  • Class IIa - reasonable to administer IV
    beta-blocker at the time of presentation who are
    hypertensive LOE B
  • Class III - IV beta-blockers should not be
    administered to patients with any of the
    following LOE A
  • Contraindications include 1) signs of heart
    failure, 2) evidence of low output state, 3) risk
    for cardiogenic shock (agegt70, SBPlt120, sinus
    tachgt110bpm, HRlt60, increased time since onset of
    STEMI), 4) or other relative contraindication
    (PRgt0.24s, heart block, active asthma)

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UFH/ LMWH in STEMI
  • Class I - Patients receiving fibrinolytics should
    receive anticoagulant therapy for a minimum of 48
    hrs, LOE C. Because of heparin induced
    thrombocytopenia, regimens other than UFH are
    recommended for patients receiving anticoagulant
    therapy gt 48 hrs, LOE A.
  • DOSE
  • UFH - 60 U/kg (max 4000 U) bolus, then 12 U/kg
    per hr drip
  • Enoxaparin - (Cr lt2.5 men, lt2.0 women)
  • For pts age lt75 give 30mg IV bolus followed
    15min later by 1 mg/kg subq.
  • For pts gt75, no IV bolus and reduce subq dose to
    0.75 mg/kg

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Clopidogrel in STEMI
  • Class I - Clopidogrel 75mg/ day should be added
    to ASA in pts with STEMI regardless of
    fibrinolytic use LOE A
  • Class IIa - In patients lt 75yo, it is reasonable
    to consider a loading dose of 300mg LOE C
  • - recent studies suggest a loading dose of
    Plavix 600mg

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