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Acute Coronary Syndromes. Robert Smith August 4, 2003. Definitions. Acute coronary syndrome is defined as myocardial ischemia due to myocardial infarction (NSTEMI or STEMI) or unstable angina

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acute coronary syndromes

Acute Coronary Syndromes

Robert Smith

August 4, 2003

  • 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 (<2 months), recent acceleration of angina (<2 months), or post revascularization angina
  • 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)
pre test probability
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 >55, smoking, DM, HTN, FamHx, hyperlipidemia, known CAD)
pathophysiology of acs
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 Prinzmetal’s 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)
pathophysiology of acs7
Pathophysiology of ACS
  • Acute coronary syndromes can also be due to secondary causes
    • Thyrotoxicosis
    • Anemia
    • Tachycardia
    • Hypotension
    • Hypoxemia
    • Aterial inflammation (infection, arteritis)
treatment of acs aspirin
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
aspirin trials
Aspirin Trials
  • VA Cooperative Study
  • Canadian Multicenter Trial
  • RISC
  • Antithrombotic Trialists Collaberation
acc aha guidelines for aspirin therapy
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)
treatment of acs nitrates
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
treatment of acs beta blockers
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
beta blocker trials
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
aha acc guidelines for beta blocker therapy
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
treatment of acs heparin
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
heparin trials
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
treatment of acs lmwh
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
lmwh trials
LMWH Trials
  • EVET
acc aha guidelines for heparin therapy
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
treatment of acs ace i
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
ace i trials
ACE-I Trials
  • GISSI-3 (Lisinopril)
  • ISIS-4 (Captopril)
  • SMILE (Zofenipril)
  • FAMIS (Fosinopril)
  • SAVE (Captopril)
  • TRACE (Trandolapril)
  • AIRE (Ramiripril)
aha acc guidelines for ace i therapy
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
treatment of acs statins
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
statin trials
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
treatment of acs iibiiia inhibitors
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
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)
aha acc guidelines for use of iibiiia inhibitors
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 >3)
timi risk score
TIMI Risk Score
  • Age >65 yrs
  • Daily ASA Therapy (>7 days prior to event)
  • Symptoms of Unstable Angina
  • Documented CAD (stenosis > 50%)
  • 3 or more traditional cardiac risk factors
  • Elevated cardiac enzymes
  • ECG changes
timi risk score29
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)
treatment of acs clopidogrel
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
aha acc guidelines for clopidogrel
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
treatment of acs emergent revascularization
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
pci trials
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)
aha acc guidelines for primary pci
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 PCI’s/yr
    • The procedure is done in a center that does more than 200 PCI’s/yr and has surgical backup
conclusions approach to chest discomfort
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
conclusions treatment of nstemi usa
Conclusions; Treatment of NSTEMI/USA
  • ASA
  • NTG (consider MSO4 if pain not relieved)
  • Beta Blocker
  • Heparin/LMWH
  • ACE-I
  • +/- Statin
  • +/- Clopidogrel (don’t give if CABG is a possibility)
  • +/- IIBIIIA inhibitors (based on TIMI risk score)
conclusions treatment of stemi
Conclusions; Treatment of STEMI
  • ASA
  • NTG (consider MSO4 if pain not relieved)
  • Beta Blocker
  • Heparin/LMWH
  • ACE-I
  • +/-Clopidogrel (based on possibility of CABG)
  • +/- Statin
  • Activate the Cath Lab!!!