DAVID L. PEARLE, M.D.DAVID L. PEARLE, M.D.
PROFESSOR OF MEDICINEPROFESSOR 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
1
Atherosclerosis
5’2” 5’2” tall tall and and 272 lbs 272 lbs * * (BMI (BMI = 50 = 50 kg/mkg/m22))
Vulnerable Plaque
No ST Elevation ST Elevation
Acute Coronary Syndrome
Uns Angina NQMI Qw MI
NSTEMI
Myocardial Infarction
UA/NSTEMI 9/00
Symptom Recognition
Call to Medical System
ED Cath LabPreHospital
Delay in Initiation of Reperfusion Therapy
Increasing Loss of Myocytes
Treatment Delayed is Treatment DeniedTreatment Delayed is Treatment Denied
3
CLINICAL EXPERIENCECLINICAL EXPERIENCE
Making the same mistake with increasing confidence over an impressive number of years
O’Donnell, Skeptics Medical Dictionary
EVIDENCE BASED MEDICINEEVIDENCE BASED MEDICINE
Perpetuating other people’s mistakes instead of your own
O’Donnell, Skeptics Medical Dictionary
Class I Benefit >>> Risk
Procedure/ Treatment SHOULD be performed/ administered
Class IIa Benefit >> RiskAdditional studies with focused objectives needed
IT IS REASONABLE to perform procedure/administer treatment
Class IIb Benefit ≥ RiskAdditional studies with broad objectives needed; Additional registry data would be helpful
Procedure/Treatment MAY BE CONSIDERED
Class III Risk ≥ BenefitNo additional studies needed
Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL
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 or not well established
is not recommendedis not indicatedshould notis not
useful/effective/beneficialmay be harmful
Applying Classification of Applying Classification of Recommendations and Level of Evidence Recommendations and Level of Evidence
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
ofcare.
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
2002 ACC/AHA UA/NSTEMI Guideline Update. Available at: www.acc.org.
High Intermediate Low
History Chest or left arm pain Chest or left arm Sx w/o intermediateSx 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, orRales
ECG New transient Fixed Q waves T-wave flattening orST-seg deviation or Abnormal ST-seg or inversion in leadsT-wave inversion T-waves not w/dominant R waveswith symptoms documented as new Normal ECG
Cardiac Elevated Normal NormalMarkers
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
ACC/AHA Guideline + 2002 Update:Overview
Yellow = updated in 2002
Potential Targets for Pharmacologic Interventions
Potential Targets for Pharmacologic Interventions
Plaque ruptureCholesterol content, Inflammation
Statins
Platelet adhesion / activation / aggregation
Aspirin, clopidogrel, GP IIb/IIIa inhibitors
Activation of clotting cascade - Thrombin
Anticoagulant agents
Myocardial ischemia / necrosis
Beta-blockers, nitrates, calcium antagonists
1
2
3
4
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*
Braunwald E et al. J Am Coll Cardiol. 2000;36:970-1062; www.acc.org 3/15/2002.
High Risk or Definite ACS
With Cath and PCILikely/Definite
ACSPossible
ACS
Aspirin+
IV heparin/LMWH*+
IV platelet GP IIb/IIIa antagonist
clopidogrel
Aspirin+
SQ LMWH*or
IV heparin
clopidogrel
Aspirin
Antithrombotic OptionsAntithrombotic 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/NSTEMIEfficacy 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
Bleeding is Associated with an Increased 30-Day Mortality in NSTEMI Patients
Potential Mechanisms for the Higher Morbidity/Morality Associated with Bleeding
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 GuidelinesACC / 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)
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 InhibitorsDirect Thrombin Inhibitors
Need continuous infusion
No antidote
Cost
Disadvantages Predictable anticoagulant
response
Inhibit soluble and fibrin-bound thrombin
Inhibit thrombin-induced platelet aggregation
No heparin-induced thrombocytopenia
Decreased bleeding complications
Advantages
Xiao Z, Theroux P. Circulation. 1998;97:251-256.
Pentasaccharide in NSTEMIPentasaccharide 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 PREFERREDEARLY INVASIVE PREFERRED
•Recurrent angina, angina at restRecurrent angina, angina at rest•Elevated cardiac biomarkersElevated cardiac biomarkers•New ST depressionNew ST depression•New HF or MRNew HF or MR•High risk noninvasiveHigh risk noninvasive•Hemodynamic instabilityHemodynamic instability•Sustained VTSustained VT•PCI within 6 mosPCI within 6 mos•Prior CABGPrior CABG•High risk score (TIMI or GRACE)High risk score (TIMI or GRACE)•LVEF <40%LVEF <40%
Acute Coronary SyndromeAcute Coronary Syndrome
Angiography
PCI CABG Medical Rx
MIRACL Study: Myocardial Ischemia Reduction With
Aggressive Cholesterol Lowering
Schwartz GG et al. JAMA. 2001;285:1711-1785.
Objective: Can statins events?
3086 patients with UA or NQWMI
Double-blind, multicenter
Patients randomized to:
– atorvastatin (80 mg/d)– placebo
0 4 8 12 16
10
20
15
5
0
Time Since Randomization, wk
Cu
mu
lati
ve In
cid
ence
, %
Placebo
Atorvastatin
4,162 patients with an Acute Coronary Syndrome < 10 days 4,162 patients with an Acute Coronary Syndrome < 10 days
ASA + Standard Medical Therapy
“Standard Therapy”Pravastatin 40 mg
“Intensive Therapy”Atorvastatin 80 mg
Duration: Mean 2 year follow-up (>925 events)
Primary Endpoint: Death, MI, Documented UA requiring hospitalization, revascularization (> 30 days after randomization), or Stroke
Primary Endpoint: Death, MI, Documented UA requiring hospitalization, revascularization (> 30 days after randomization), or Stroke
PROVE IT - TIMI 22: PROVE IT - TIMI 22: Study DesignStudy Design
2x2 Factorial: Gatifloxacin vs. placebo
Double-blindDouble-blind
Changes from (Post-ACS) Changes from (Post-ACS) Baseline in Median LDL-CBaseline in Median LDL-C
Note: Changes in LDL-C may differ from prior trials: Note: Changes in LDL-C may differ from prior trials: • 25% of patients on statins prior to ACS event25% of patients on statins prior to ACS event• ACS response lowers LDL-C from true baselineACS response lowers LDL-C from true baseline
LDL-C (mg/dL)
20
40
60
80
100
120
Rand. 30 Days 4 Mos. 8 Mos. 16 Mos. Final
Pravastatin 40mg
Atorvastatin 80mg49% 49%
21%21%
P<0.001P<0.001
Median LDL-C (Q1, Q3)Median LDL-C (Q1, Q3)
95 (79, 113)95 (79, 113)
62 (50, 79) 62 (50, 79)
<24h
% % with with EvenEven
tt
00 33 1818 2121 2424 2727 303066 99 1212 1515
2020
1515
1010
55
00
Months of Follow-up
All-Cause Death, Non-Fatal MI, or Urgent Revascularization
All-Cause Death, Non-Fatal MI, or Urgent Revascularization
Pravastatin 40mgPravastatin 40mg16.7%16.7%
Atorvastatin 80mgAtorvastatin 80mg12.9%12.9%
25% RR25% RRP = 0.0004P = 0.0004
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 inhibitorB = Beta blockerC = Cholesterol lowering agentD = Don’t smoke, DietE = Exercise
HOW DISH WASHERS WORK
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