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					DAVID L. PEARLE, M.D.
    PROFESSOR OF MEDICINE
                  Chest Pain
• One of the most common complaints of patients
  being seen in the Emergency Department

• 5 million patients/year seen with this symptom

• Need to distinguish patients with life threatening
  illness from those with less serious illness

• Missed MI is most frequent malpractice issue in
  ED medicine
      Patients with chest pain
• 15% will have myocardial infarction

• 30-35% will have acute coronary syndrome
  (unstable angina)

• 45-50% will have non-cardiac pain
                Epidemiology
•   1.5 million MI’s per year
•   Accounts for 25 % of deaths
•   More than 60 % of deaths are sudden
•   Almost 2 million CCU admissions per year
    – Approx. 1/3 “rule in”
       DIFFERENTIAL DX
• Acute myocardial infarction (STEMI vs
  Non STEMI)
• Acute coronary syndrome (ACS)
• Aortic dissection
• Pulmonary embolus
• Pericarditis
• Pneumonia
   DIFFERENTIAL DX (cont)
• Gastroesophageal reflux (GERD)
• Musculoskeletal
• Psychosocial
Atherosclerosis




                  1
5’2” tall
and
272 lbs
* (BMI =
50
kg/m2)
Vulnerable Plaque
                 Acute Coronary Syndrome
UA/NSTEMI 9/00




             No ST Elevation       ST Elevation
                     NSTEMI


                           Myocardial Infarction
          Uns Angina       NQMI        Qw MI
        Treatment Delayed is Treatment Denied




 Symptom        Call to         PreHospital                ED             Cath Lab
Recognition Medical System


                                              Increasing Loss of Myocytes

                             Delay in Initiation of Reperfusion Therapy
3
CLINICAL EXPERIENCE


Making the same mistake with increasing
confidence over an impressive number of
years

                  O’Donnell, Skeptics Medical
                  Dictionary
EVIDENCE BASED MEDICINE



Perpetuating other people’s mistakes instead of
                   your own


                     O’Donnell, Skeptics Medical
                     Dictionary
                  Applying Classification of
             Recommendations and Level of Evidence
Class I                Class IIa                    Class IIb                     Class III

Benefit >>> Risk       Benefit >> Risk              Benefit ≥ Risk                Risk ≥ Benefit
                       Additional studies with      Additional studies with       No additional studies
                       focused objectives           broad objectives needed;      needed
                       needed                       Additional registry data
                                                    would be helpful              Procedure/Treatment
Procedure/ Treatment   IT IS REASONABLE to                                        should NOT be
SHOULD be              perform                      Procedure/Treatment           performed/administered
performed/             procedure/administer         MAY BE CONSIDERED             SINCE IT IS NOT
administered           treatment                                                  HELPFUL AND MAY BE
                                                                                  HARMFUL


should                 is reasonable                may/might be considered        is not recommended
is recommended         can be useful/effective/     may/might be reasonable        is not indicated
is indicated             beneficial                 usefulness/effectiveness is    should not
is useful/effective/   is probably recommended or    unknown /unclear/uncertain    is not
  beneficial             indicated                   or not well established         useful/effective/beneficial
                                                                                   may be harmful
 Level of Evidence
Level of Evidence A: Data derived from
multiple randomized clinical trials or meta-
                analyses.
  Level of Evidence B: Data derived
    from a single randomized trial, or
          nonrandomized studies.

          Level of Evidence C:
                    Only
           consensus opinion
            of experts, case
               studies, or
                standard
                    of
                  care.
                 ACC/AHA Class I
               Recommendations for
              Evaluation of Chest Pain
        Patients with suspected ACS with chest
         discomfort at rest for >20 min,
         hemodynamic instability, or recent
         presyncope or syncope should be strongly
         considered for immediate referral to an ED
         or to a specialized chest pain unit
        Assess likelihood of CAD
        Assess risk of adverse events
2002 ACC/AHA UA/NSTEMI Guideline Update. Available at www.acc.org.
 Likelihood of ACS Secondary to CAD
                 High                         Intermediate            Low
History          Chest or left arm pain       Chest or left arm       Sx w/o intermediate
                 Sx as in prior angina        pain; age >70 yr        likelihood character-
                 Known history of CAD         Male sex; DM            istics; recent cocaine
Exam             Transient MR,                Extracardiac            Chest pain
                 Hypotension,                 vascular                reproduced
                 Diaphoresis,                 disease                 by palpation
                 Pulmonary edema, or
                 Rales
ECG              New transient                Fixed Q waves           T-wave flattening or
                 ST-seg deviation or          Abnormal ST-seg or      inversion in leads
                 T-wave inversion             T-waves not             w/dominant R waves
                 with symptoms                documented as new       Normal ECG
Cardiac          Elevated                     Normal                  Normal
Markers



2002 ACC/AHA UA/NSTEMI Guideline Update. Available at: www.acc.org.
ACC/AHA Guideline + 2002 Update:
          Overview
         Sx suspected ACS  Eval in ED
         Assess likelihood of CAD
         Risk stratification
         Target therapy: More aggressive Rx
          in higher risk patients
         Anti-ischemic, anti-thrombotic Rx, anti-
          platelet
         Invasive vs. conservative strategy
         Discharge planning
Yellow = updated in 2002
                                                      Potential Targets for
                                               Pharmacologic Interventions

 1      Plaque rupture
        Cholesterol content, Inflammation
                Statins
 2      Platelet adhesion / activation / aggregation
                Aspirin, clopidogrel, GP IIb/IIIa inhibitors
 3      Activation of clotting cascade - Thrombin
                 Anticoagulant agents
 4      Myocardial ischemia / necrosis
                 Beta-blockers, nitrates, calcium antagonists


Fuster et al. N Engl J Med. 1992;326:242-318
Falk et al. Circulation. 1995;92:657-671
   ACC/AHA Guideline :
   Anti-Ischemic Therapy
1. Bed rest with continuous ECG monitoring
2. Nitroglycerin, started SL then IV for ongoing
   ischemia
3. Supplemental O2 for patients with cyanosis or
   respiratory distress; confirm SaO2 >90%
4. Morphine sulfate IV for pain, anxiety, CHF
5. Beta-blocker started and continued. Calcium
   antagonist if beta-blocker and/or nitrates
   contraindicated or insufficient
6. An ACEI if LVEF <40%, HF, or hypertension
   persists
ACC/AHA Guideline + 2002 Update:
                  Recommendations
             for Antithrombotic Therapy*
   High Risk or
   Definite ACS                        Likely/Definite                       Possible
 With Cath and PCI                          ACS                                ACS
       Aspirin                             Aspirin                               Aspirin
          +                                   +
 IV heparin/LMWH*                        SQ LMWH*
          +                                  or
     IV platelet                         IV heparin
     GP IIb/IIIa
     antagonist                         clopidogrel

     clopidogrel


Braunwald E et al. J Am Coll Cardiol. 2000;36:970-1062; www.acc.org 3/15/2002.
                                     Antithrombotic Options

• Unfractionated heparin (UFH)
   – Multiple anticoagulant effects including inhibition
     of factors Xa (thrombin generation) and IIa (thrombin activity) by
     enhancing antithrombin III activity

• Low-molecular-weight heparin (LMWH)
   – Anti-Xa activity exceeds anti-IIa activity

• Direct thrombin inhibitors (Bivalirudin)
   – “Pure” IIa effect (thrombin activity)

• Pentasaccharide
   – “Pure” Xa effect (thrombin generation)
    Efficacy Versus Bleeding in UA/NSTEMI

• In the last decade new antithrombotic
  therapies have increased anti-ischemic
  efficacy at the price of increasing bleeding
• Bleeding is associated with a higher risk of
  morbidity and mortality
• The previous focus on efficacy and ischemic
  complications is now balanced by recognition
  of the risk associated with bleeding
Bleeding is Associated with an Increased
     30-Day Mortality in NSTEMI Patients
              Potential Mechanisms for the Higher
       Morbidity/Morality Associated with Bleeding

• Rebound ischemic events due to
  activation of clotting after the end of
  treatment
• Cessation of antithrombotic therapies
  after a bleeding event
• Adverse effects of hypotension
• Adverse effects of transfusion
• Common risk factors for bleeding and
  adverse outcome
                ACC / AHA ACS Guidelines

Clopidogrel has a much more prominent role: (CURE)
 As an addition to aspirin in the initial medical therapy of
   conservatively-managed patients
      (Class I – level of evidence B)
 In those patients in whom a PCI is planned [the exact timing
   of when it should be initiated is not addressed]
      (Class I – level of evidence B)
 For patients in whom a CABG is planned, clopidogrel should
   be withheld for 5-7 days
      (Class I – level of evidence B)
                                           Direct Thrombin Inhibitors
                         Advantages                     Disadvantages
               Predictable anticoagulant           Need continuous infusion
                response
                                                    No antidote
               Inhibit soluble and fibrin-
                bound thrombin                      Cost

               Inhibit thrombin-induced
                platelet aggregation
               No heparin-induced
                thrombocytopenia
               Decreased bleeding
                complications




Xiao Z, Theroux P. Circulation. 1998;97:251-256.
                    Pentasaccharide in NSTEMI

• Acutely, pentasaccharide reduces risk of death
  or MI to a degree similar to enoxaparin
• Bleeding complications are reduced
• Long-term events are less frequent with
  pentasaccharide
• There may be an association between less
  acute bleeding and better long-term outcomes
• Additional UFH is required if PCI is performed
EARLY INVASIVE PREFERRED
•Recurrent angina, angina at rest
•Elevated cardiac biomarkers
•New ST depression
•New HF or MR
•High risk noninvasive
•Hemodynamic instability
•Sustained VT
•PCI within 6 mos
•Prior CABG
•High risk score (TIMI or GRACE)
•LVEF <40%
Acute Coronary Syndrome




          Angiography

    PCI         CABG      Medical Rx
                MIRACL Study:
       Myocardial Ischemia Reduction With
        Aggressive Cholesterol Lowering
Objective: Can statins  events?
   3086 patients with                                                   20




                                               Cumulative Incidence, %
    UA or NQWMI                                                                                Placebo
                                                                         15
   Double-blind,                                                                                   Atorvastatin
    multicenter                                                          10

   Patients randomized to:                                               5

        – atorvastatin                                                    0
          (80 mg/d)                                                           0        4       8         12      16
        – placebo                                                                 Time Since Randomization, wk


Schwartz GG et al. JAMA. 2001;285:1711-1785.
      PROVE IT - TIMI 22:
      Study Design

     4,162 patients with an Acute Coronary Syndrome < 10 days

                     ASA + Standard Medical Therapy
    Double-blind
            “Standard Therapy”           “Intensive Therapy”
             Pravastatin 40 mg            Atorvastatin 80 mg

                   2x2 Factorial: Gatifloxacin vs. placebo

              Duration: Mean 2 year follow-up (>925 events)

rimary Endpoint: Death, MI, Documented UA requiring hospitalization
    revascularization (> 30 days after randomization), or Stroke
                     Changes from (Post-ACS)
                     Baseline in Median LDL-C
     120                                                     Median LDL-C (Q1, Q3)

     100                                                         95 (79, 113)
                                  Pravastatin 40mg
                        21%
 LDL-C 80
(mg/dL                                                           62 (50, 79)
   ) 60
                                  Atorvastatin 80mg
                        49% 
      40
                                              P<0.001
      20
            <24h Rand. 30 Days 4 Mos. 8 Mos. 16 Mos. Final

               Note: Changes in LDL-C may differ from prior trials:
                  • 25% of patients on statins prior to ACS event
                  • ACS response lowers LDL-C from true baseline
          All-Cause Death, Non-Fatal MI, or
              Urgent Revascularization


     20
 %
                      Pravastatin 40mg
with                       16.7%
Even 15
  t
     10
                                      Atorvastatin 80mg
                                            12.9%
      5
                              25% RR
                             P = 0.0004
      0

          0   3   6     9   12   15   18   21   24   27   30
                        Months of Follow-up
     DISCHARGE PLANNING
•   ASA, clopidogrel
•   BB
•   ACEI
•   BP control
•   Lipid management
•   DM management
•   Smoking cessation
DISCHARGE PLANNING contd
•   Weight management
•   Exercise program
•   Cardiac rehab
•   Pt education
•   Influenza vaccine
•   Depression screening
•   Generally advise against HRT in women
            ABCDE

A = Aspirin, ACE inhibitor
B = Beta blocker
C = Cholesterol lowering agent
D = Don’t smoke, Diet
E = Exercise
HOW DISH WASHERS WORK

				
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