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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
