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Acute Coronary Syndromes

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Title: Acute Coronary Syndromes


1
Acute Coronary Syndromes
  • Robert Smith
  • August 4, 2003

2
Definitions
  • Acute coronary syndrome is defined as myocardial
    ischemia due to myocardial infarction (NSTEMI or
    STEMI) or unstable angina
  • Unstable angina is defined as angina at rest, new
    onset exertional angina (lt2 months), recent
    acceleration of angina (lt2 months), or post
    revascularization angina

3
(No Transcript)
4
Diagnosis
  • Dx of acute coronary syndrome is based on
    history, physical exam, ECG, cardiac enzymes
  • Patients can then be divided into several groups
  • Non-cardiac chest pain (i.e., Gastrointestinal,
    musculoskeletal, pulmonary embolus)
  • Stable angina
  • Unstable angina
  • Myocardial infarction (STEMI or NSTEMI)
  • Other cardiac causes of chest pain (i.e., aortic
    dissection, pericarditis)

5
Pre-test Probability
  • In the absence of abnormal findings on physical
    exam, ECG, or enzymes, the pre-test probability
    of acute coronary syndrome must be determined by
    the clinician
  • A good history is crucial (is the chest pain
    typical or atypical what are the associated
    symptoms)
  • Determination of risk factors is also crucial
    (male, age gt55, smoking, DM, HTN, FamHx,
    hyperlipidemia, known CAD)

6
Pathophysiology of ACS
  • Plaque rupture and subsequent formation of
    thrombus this can be either occlusive or
    non-occlusive (STEMI, NSTEMI, USA)
  • Vasospasm such as that seen in Prinzmetals
    angina, cocaine use (STEMI, NSTEMI, USA)
  • Progression of obstructive coronary
    atherosclerotic disease (USA)
  • In-stent thrombosis (early post PCI)
  • In-stent restenosis (late post PCI
  • Poor surgical technique (post CABG)

7
Pathophysiology of ACS
  • Acute coronary syndromes can also be due to
    secondary causes
  • Thyrotoxicosis
  • Anemia
  • Tachycardia
  • Hypotension
  • Hypoxemia
  • Aterial inflammation (infection, arteritis)

8
Treatment of ACS Aspirin
  • Aspirin is an antiplatelet agent that initiates
    the irreversible inhibition of cyclooxygenase,
    thereby preventing platelet production of
    thromboxane A2 and decreasing platelet
    aggregation
  • Administration of ASA in ACS reduces cardiac
    endpoints

9
Aspirin Trials
  • VA Cooperative Study
  • Canadian Multicenter Trial
  • RISC
  • Antithrombotic Trialists Collaberation
  • PURSUIT

10
ACC/AHA Guidelines for Aspirin Therapy
  • Aspirin should be given in a dose of 75-325
    mg/day to all patients with ACS unless there is a
    contraindication (in which case, clopidogrel
    should be given)

11
Treatment of ACS Nitrates
  • Nitroglycerin is considered a cornerstone of
    anti-anginal therapy, despite little objective
    evidence for its benefit
  • Benefit is thought to occur via reduction in
    myocardial O2 demand secondary to venodilation
    induced reduction in preload as well as coronary
    vasodilation and afterload reduction
  • Titrate to relief of chest pain chest pain
    death of myocardial cells
  • No documented mortality benefit

12
Treatment of ACS Beta Blockers
  • Beta Blockers reduce myocardial oxygen demand by
    reducing heart rate, contractility, and
    ventricular wall tension
  • Administration of beta blockers in ACS reduces
    cardiac endpoints

13
Beta Blocker Trials
  • HINT (metoprolol)
  • Beta Blocker Heart Attack Trial (propranolol)
  • Esmolol vs. placebo
  • Carvedilol vs. placebo
  • Propranolol vs. placebo
  • Overall, treatment with beta blockers reduces
    primary endpoints when compared to placebo

14
AHA/ACC Guidelines for Beta Blocker Therapy
  • Intravenous beta blockers should be used
    initially in all patients (without
    contraindication) followed by oral beta blockers
    with the goal being decrease in heart rate to 60
    beats per minute
  • A combination of beta blockers and nitrates can
    be viewed as first line therapy in all patients
    with ACS

15
Treatment of ACS Heparin
  • Heparin (unfractionated heparin or UFH) has
    traditionally been the mainstay of therapy in
    acute coronary syndromes as its efficacy has been
    documented in several large, randomized trials

16
Heparin Trials
  • Heparin/Atenolol Trial
  • The Canadian Heparin/Aspirin Trial
  • The RISC Trial
  • Overall, UFH therapy generally results in an
    important clinical benefit when compared to
    placebo. It is more effective when given in
    continuous infusion rather than intermittent
    boluses

17
Treatment of ACS LMWH
  • More recent studies indicate that low molecular
    weight heparin is also effective in the reduction
    of end points such as myocardial infarction or
    death
  • Some studies report that LMWH, when used in
    combination with ASA, may be superior to
    continuous infusion of Heparin

18
LMWH Trials
  • FRISC
  • TIMI IIB
  • ESSENCE
  • INTERACT
  • EVET

19
ACC/AHA Guidelines for Heparin Therapy
  • All patients with acute coronary syndromes should
    be treated with a combination of ASA (325 mg/day)
    and heparin (bolus followed by continuous
    infusion with goal of PTT 1-2.5X control) or ASA
    and low molecular weight heparin unless one of
    the drugs is contraindicated

20
Treatment of ACS ACE-I
  • The best documented mechanism by which these
    agents act is to reduce ventricular remodeling
    over days to weeks after myocardial damage.
    However, there is data that a mortality benefit
    exists when these agents are used early in the
    course of ACS
  • Administration of ACE-I in ACS reduces cardiac
    endpoints

21
ACE-I Trials
  • GISSI-3 (Lisinopril)
  • ISIS-4 (Captopril)
  • SMILE (Zofenipril)
  • FAMIS (Fosinopril)
  • SAVE (Captopril)
  • TRACE (Trandolapril)
  • AIRE (Ramiripril)

22
AHA/ACC Guidelines for ACE-I Therapy
  • ACE-I should be administered to all patients in
    the first 24 hours of ACS provided hypotension
    and other clear cut contraindications are absent

23
Treatment of ACS Statins
  • Statins may be of benefit in ACS
  • Possible mechanisms include plaque stabilization,
    reversal of endothelial dysfunction, decreased
    thrombogenicity, and reduction of inflammation

24
Statin Trials
  • MIRACL (modest benefit in cardiac endpoints, no
    mortality benefit)
  • SYMPHONY (no benefit)
  • There is no AHA/ACC class I indication for use of
    statin therapy in ACS

25
Treatment of ACS IIBIIIA Inhibitors
  • More potent inhibition of platelet aggregation
    may be of importance in patients with ACS that is
    associated with unstable coronary lesion and
    thrombus formation. This can be achieved by the
    use of GP IIBIIIA inhibitors
  • Administration of IIBIIIA inhibitors reduces
    cardiac endpoints

26
IIBIIIA Trials
  • PRISM-PLUS (Tirofiban prior to PCI)
  • EPIC (Abciximab prior to PCI)
  • CAPTURE (Abciximab prior to PCI)
  • GUSTO IV-ACS (Abciximab no PCI)
  • PARAGON (Lamifiban no PCI)
  • PURSUIT (Eptifibatide -- no PCI)
  • RESTORE (Tirofiban no PCI)

27
AHA/ACC Guidelines for use of IIBIIIA inhibitors
  • A IIBIIIA inhibitor should be administered to all
    patients in whom a percutaneous intervention is
    planned (in addition to heparin/ASA)
  • Eptifibatide or Tirofiban should be administered
    to patients with ACS in whom PCI is not planned
    if other high risk features are present (TIMI
    risk score gt3)

28
TIMI Risk Score
  • Age gt65 yrs
  • Daily ASA Therapy (gt7 days prior to event)
  • Symptoms of Unstable Angina
  • Documented CAD (stenosis gt 50)
  • 3 or more traditional cardiac risk factors
  • Elevated cardiac enzymes
  • ECG changes

29
TIMI Risk Score
  • Score of 3 or less low risk
  • Score of 4-5 intermediate risk (use IIBIIIA)
  • Score of 6-7 high risk (use IIBIIIA)

30
Treatment of ACS Clopidogrel
  • Clopidogrel is a potent antiplatelet agent
  • It should be administered to all patients who
    cannot take ASA
  • The CURE trial suggests a benefit to adding
    Clopidogrel to ASA/Heparin in patients going for
    PCI
  • Give 300 mg loading dose followed by 75 mg/day

31
AHA/ACC Guidelines for Clopidogrel
  • Clopidogrel should be administered to patients
    who cannot take ASA because of hypersensitivity
    or gastrointestinal intolerance
  • In hospitalized patients in whom an early,
    noninterventional approach is planned,
    clopidogrel should be added to ASA as soon as
    possible on admission and administered for at
    least 1 month and up to 9 months. Do not use
    clopidogrel if there is any possibility patient
    may be candidate for CABG

32
Treatment of ACS Emergent Revascularization
  • In the setting of STEMI primary PCI is associated
    with better outcomes than thrombolysis
  • Emergent PCI is also indicated in the setting of
    a new LBBB

33
PCI Trials
  • PAMI (PTCA vs. thrombolysis)
  • Netherlands Trials (PTCA vs. thrombolysis)
  • GUSTO IIB (PTCA vs. thrombolysis)
  • DANAMI-2 (stenting vs. thrombolysis)
  • STAT (stenting vs. thrombolysis)

34
AHA/ACC Guidelines for Primary PCI
  • Primary PCI is indicated as an alternative to
    thrombolysis when the following criteria are met
  • STEMI or new LBBB
  • Can undergo PCI within 12 hours of the onset of
    symptoms
  • The MD doing the intervention does more than 75
    PCIs/yr
  • The procedure is done in a center that does more
    than 200 PCIs/yr and has surgical backup

35
Conclusions Approach to Chest Discomfort
  • Good History and Physical (note time and duration
    of symptoms)
  • Careful evaluation of ECG (compare to previous
    when possible)
  • Check Cardiac Enzymes
  • Monitor on Telemetry
  • Oxygen

36
Conclusions Treatment of NSTEMI/USA
  • ASA
  • NTG (consider MSO4 if pain not relieved)
  • Beta Blocker
  • Heparin/LMWH
  • ACE-I
  • /- Statin
  • /- Clopidogrel (dont give if CABG is a
    possibility)
  • /- IIBIIIA inhibitors (based on TIMI risk score)

37
Conclusions Treatment of STEMI
  • ASA
  • NTG (consider MSO4 if pain not relieved)
  • Beta Blocker
  • Heparin/LMWH
  • ACE-I
  • /-Clopidogrel (based on possibility of CABG)
  • IIBIIIA
  • /- Statin
  • Activate the Cath Lab!!!
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