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DAVID L. PEARLE, M.D. DAVID L. PEARLE, M.D. PROFESSOR OF MEDICINE PROFESSOR OF MEDICINE

Stable Angina, Unstable Angina, and - Coronary Artery Disease

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Page 1: Stable Angina, Unstable Angina, and - Coronary Artery Disease

DAVID L. PEARLE, M.D.DAVID L. PEARLE, M.D.

PROFESSOR OF MEDICINEPROFESSOR OF MEDICINE

Page 2: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 3: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 4: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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”

Page 5: Stable Angina, Unstable Angina, and - Coronary Artery Disease

DIFFERENTIAL DX

• Acute myocardial infarction (STEMI vs Non STEMI)

• Acute coronary syndrome (ACS)

• Aortic dissection

• Pulmonary embolus

• Pericarditis

• Pneumonia

Page 6: Stable Angina, Unstable Angina, and - Coronary Artery Disease

DIFFERENTIAL DX (cont)

• Gastroesophageal reflux (GERD)

• Musculoskeletal

• Psychosocial

Page 7: Stable Angina, Unstable Angina, and - Coronary Artery Disease

1

Atherosclerosis

Page 8: Stable Angina, Unstable Angina, and - Coronary Artery Disease

5’2” 5’2” tall tall and and 272 lbs 272 lbs * * (BMI (BMI = 50 = 50 kg/mkg/m22))

Page 9: Stable Angina, Unstable Angina, and - Coronary Artery Disease
Page 10: Stable Angina, Unstable Angina, and - Coronary Artery Disease

Vulnerable Plaque

Page 11: Stable Angina, Unstable Angina, and - Coronary Artery Disease
Page 12: Stable Angina, Unstable Angina, and - Coronary Artery Disease

No ST Elevation ST Elevation

Acute Coronary Syndrome

Uns Angina NQMI Qw MI

NSTEMI

Myocardial Infarction

UA/NSTEMI 9/00

Page 13: Stable Angina, Unstable Angina, and - Coronary Artery Disease
Page 14: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 15: Stable Angina, Unstable Angina, and - Coronary Artery Disease

3

Page 16: Stable Angina, Unstable Angina, and - Coronary Artery Disease

CLINICAL EXPERIENCECLINICAL EXPERIENCE

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

O’Donnell, Skeptics Medical Dictionary

Page 17: Stable Angina, Unstable Angina, and - Coronary Artery Disease

EVIDENCE BASED MEDICINEEVIDENCE BASED MEDICINE

Perpetuating other people’s mistakes instead of your own

O’Donnell, Skeptics Medical Dictionary

Page 18: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 19: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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.

Page 20: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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.

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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

Page 22: Stable Angina, Unstable Angina, and - Coronary Artery Disease
Page 23: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 24: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 25: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 26: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 27: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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)

Page 28: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

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Bleeding is Associated with an Increased 30-Day Mortality in NSTEMI Patients

Bleeding is Associated with an Increased 30-Day Mortality in NSTEMI Patients

Page 30: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 31: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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)

Page 32: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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.

Page 33: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

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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%

Page 37: Stable Angina, Unstable Angina, and - Coronary Artery Disease

Acute Coronary SyndromeAcute Coronary Syndrome

Angiography

PCI CABG Medical Rx

Page 38: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 39: Stable Angina, Unstable Angina, and - Coronary Artery Disease
Page 40: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 41: Stable Angina, Unstable Angina, and - Coronary Artery Disease

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

Page 42: Stable Angina, Unstable Angina, and - Coronary Artery Disease

% % 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

Page 43: Stable Angina, Unstable Angina, and - Coronary Artery Disease

DISCHARGE PLANNING

• ASA, clopidogrel

• BB

• ACEI

• BP control

• Lipid management

• DM management

• Smoking cessation

Page 44: Stable Angina, Unstable Angina, and - Coronary Artery Disease

DISCHARGE PLANNING contd

• Weight management

• Exercise program

• Cardiac rehab

• Pt education

• Influenza vaccine

• Depression screening

• Generally advise against HRT in women

Page 45: Stable Angina, Unstable Angina, and - Coronary Artery Disease

ABCDE

A = Aspirin, ACE inhibitorB = Beta blockerC = Cholesterol lowering agentD = Don’t smoke, DietE = Exercise

Page 46: Stable Angina, Unstable Angina, and - Coronary Artery Disease
Page 47: Stable Angina, Unstable Angina, and - Coronary Artery Disease

HOW DISH WASHERS WORK

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