Transcript Grand Rounds Series - Northwestern Cardiology Fellows
Unstable Angina and Non-ST elevation Myocardial Infarction
John Blair, MD
Unstable Angina / Non ST-Elevation Myocardial Infarction (UA/NSTEMI)
•
Pathophysiology
•
Diagnosis
•
Initial Therapy
•
Risk-Stratification
•
Invasive vs Conservative
•
Post AMI Care
www.
Clinical trial results.org
UA / NSTEMI
• Pathophysiology •
Diagnosis
•
Initial Therapy
•
Risk-Stratification
•
Invasive vs Conservative
•
Post AMI Care
www.
Clinical trial results.org
Sudden Thrombus or Thromboembolism Superficial Erosion Ruptured Fibrous Cap Modified from Libby P Circ 104:365,2001 www.
Clinical trial results.org
Hamm Lancet 358:1533,2001
Presentation Working Dx
Ischemic Discomfort Acute Coronary Syndrome
Davies MJ Heart 83:361, 2000
ECG
No ST Elevation NSTEMI
Biochem. Marker Final Dx
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Unstable Angina Clinical trial results.org
ST Elevation
Myocardial Infarction
NQMI Qw MI
Causes of UA/NSTEMI
•
Thrombus or thromboembolism
, usually arising on disrupted or eroded plaque –
Most Common Cause.
• Dynamic obstruction – coronary spasm or vasoconstriction • Progressive mechanical obstruction to coronary flow – ie restenosis after PCI • Coronary arterial inflammation • Coronary artery dissection •
Secondary UA
– Increasing oxygen demands in the setting of a fixed lesion.
www.
Clinical trial results.org
Acute Coronary Syndromes
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Pathophysiology
• Diagnosis •
Initial Therapy
•
Risk-Stratification
•
Invasive vs Conservative
•
Post AMI Care
www.
Clinical trial results.org
Likelihood that Signs and Symptoms Represent ACS Feature
History Exam ECG Cardiac Markers
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High Likelihood
Chest/L arm pain similar to prior angina, known CAD MR murmur, hypotension, diaphoresis, pulm edema, rales New transient ST deviation (>1mm) or TWI in multiple leads Elevated TnI, TnT, CK-MB
Intermediate Likelihood
Chest/L arm pain, >70 y/o, Male, DM, Extracardiac vascular disease Fixed Q waves, ST depression 0.5-1mm, TWI >1mm Normal
Low Likelihood
Probable ischemia, recent cocaine use CP on palpation TWI <1mm in leads with dominant R waves Normal
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Algorithm for Evaluation and Management of Patients Suspected of Having ACS
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Timing of Release of Various Biomarkers After Acute Myocardial Infarction
Acute Coronary Syndromes
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Pathophysiology
•
Diagnosis
• Initial Therapy •
Risk-Stratification
•
Invasive vs Conservative
•
Post AMI Care
www.
Clinical trial results.org
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
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Statins
Clinical trial results.org
• Increases oxygen supply to ischemic tissue • Start at 4L/min • Use caution in COPD patients
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
www.
Statins
Clinical trial results.org
• Blocks formation of thromboxane A 2 and thus prevents platelet aggregation • Reduces mortality, reinfarction, and stroke in patients with MIs
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade • Statins
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• Blocks catecholamines from binding to β-adrenergic receptors • Reduces myocardial demand by reducing HR, BP, contractility • Decreases incidence of primary VF
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
www.
Statins
Clinical trial results.org
• Dilates coronary arteries • Increases venous dilation and therefore decreases venous return • Decreases myocardial demand by decreasing preload
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
www.
Statins
Clinical trial results.org
• Reduces pain of ischemia and anxiety indirect effect on catecholamines • May dilate coronary arteries and reduce preload decreases myocardial oxygen demand
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
www.
Statins
Clinical trial results.org
• Heparins - Indirect thrombin inhibitors including LMWH • DTI - Direct thrombin inhibitors • Reduce further coagulation
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
www.
Statins
Clinical trial results.org
• Blocks platelet receptor so platelets cannot bind fibrinogen and form clots • caution in renal disease (tirofiban, ebtifbatide) and with thrombocytopenia (abciximab)
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
www.
Statins
Clinical trial results.org
• Blocks the ADP receptor on platelets which also prevents fibrinogen binding and clot formation • Bleeding risks during CABG have limited its immediate use until coronary anatomy defined
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
www.
Statins
Clinical trial results.org
• reduces peripheral vasoconstriction and blood pressure • Alters post-MI LV remodeling
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
www.
Statins
Clinical trial results.org
• reduces fibrosis, hypokalemia, and arrhythmias • beneficial in high-risk post-AMI LV dysfunction
Treatment
• • • • • • Oxygen Aspirin Beta-blocker Nitroglycerin Morphine Heparins, DTIs • • IIb/IIIa inhibitors Plavix • • ACE/ARB Aldosterone Blockade •
www.
Statins
Clinical trial results.org
• reduce LDL • may decrease inflammation
Initial Therapy
• Anti-ischemic and Analgesic therapy • Anti-platelet therapy • Anti-coagulant therapy
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ACC/AHA Guidelines – Updated in 2007 from 2002 www.
Clinical trial results.org
Anti-ischemic and Analgesic Therapy
•
Bed/chair rest
– Class I, C •
O2
for SaO2 < 90%, respiratory distress, or hypoxemia – Class I, B •
NTG
0.4 mg sl q 5 min x 3 doses, then gtt for ongoing ischemic discomfort – Class I, C •
NTG
iv within 48h for persistent ischemia, HF, or HTN. Should not preclude use of BB – Class I, B •
Oral BB
therapy within 24h without 1) HF, 2) low output, 3) risk of shock, 4) relative contraindications – Class I, B
www.
Clinical trial results.org
Anti-ischemic and Analgesic Therapy
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CCB
(nondihydropyridine) if contraindication for BB in the absence of contraindications – Class I, B •
ACE inhibitor
for LVEF <0.40 and no hypotension (SBP <100 or <30 below baseline) – Class I, A •
ARB
if intolerant to ACE inhibitor – Class I, A • NSAIDS should be discontinued – Class I, C
www.
Clinical trial results.org
Anti-Platelet Therapy
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ASA
– started immediately and continued indefinitely – Class I, A •
Plavix
– loading dose (300-600mg)* plus maintenance 75 mg if ASA intolerant – Class I, A • If h/o GIB, PPI plus anti-platelet therapy – Class I, B •
GP IIB/IIIA
therapy depends on strategy chosen (more on this later) * Risk/benefit to higher loading dose regimens is yet to be determined
www.
Clinical trial results.org
Anti-Coagulant Therapy
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Anticoagulant
antiplatelet therapy as soon as possible after presentation Therapy should be added to • Choice of anticoagulant depends on the strategy chosen (more on this later)
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There is an Incremental Benefit to ASA, UFH/LMWH, and GPIIb/IIIa Therapy www.
Acute Coronary Syndromes
•
Pathophysiology
•
Diagnosis
•
Initial Therapy
• Risk-Stratification •
Invasive vs Conservative
•
Post AMI Care
www.
Clinical trial results.org
Kaplan-Meier Estimates of Probability of Death Based on Admission Electrocardiogram www.
Clinical trial results.org
–13 (127)
Troponin I Levels to Predict the Risk of Mortality in Acute Coronary Syndromes Antman EM, Tanasijevic MJ, Thompson B, et al. N Engl J Med 1996;335:1342 –9 (201) www.
Clinical trial results.org
TIMI Risk Score – Cardiac Events by 14 Days (TIMI 11B, ESSENCE) www.
Clinical trial results.org
GRACE Prediction Score – All-cause Mortality Within 6 Months of Discharge Eagle KA, Lim MJ, Dabbous OH, et al. JAMA 2004;291:2727-33(168) www.
Clinical trial results.org
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What is Elevated Risk?
Acute Coronary Syndromes
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Pathophysiology
•
Diagnosis
•
Initial Therapy
•
Risk-Stratification
• Invasive vs Conservative •
Post AMI Care
www.
Clinical trial results.org
Choose A Strategy
• Initial Conservative – Angiography only if patient
fails medical management
(refractory or resting angina)
or
has
objective evidence of ischemia
(stress testing) • Initial Invasive – Angiography before failure of medical management or stress testing – –
Immediate Deferred
angiography (ISAR-COOL) or Angiography (all other trials – 12-48h)
www.
Clinical trial results.org
Choose A Strategy - Rationale
• Initial Conservative – Early trials demonstrate similar efficacy (TIMI IIIB, MATE, VANQWISH, RITA-2) – Aggressive antiplatelet and anticoagulant therapy has reduced events • Initial Invasive – Rapidly identify the 10-20% with nonocclusive CAD and the 20% with 3v CAD
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Less Events in Early Invasive Strategy
Choose A Strategy – Guidelines
• Initial invasive – Refractory angina or hemodynamic/electrical instability (Class I, B) – Initially stabilized patients without contraindications and with elevated risk for events (Class I, A) • Initial Conservative – May be considered in patients with elevated risk (Class IIb,B) – May consider physician or patient preference (Class IIb,C) – Women with low-risk features (Class I, B)
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Clinical trial results.org
Anticoagulants and Antiplatelets – Initial Invasive Strategy Recommendation Evidence
Enoxaparin, UFH (I, A), bivalirudin, or fondaparinux (I, B) ASAP
Plavix or IIb/IIIa
inhibitor prior to angiography* (I, A) *Abciximab only if no delay to cath and PCI likely (I, B)
Enoxaparin:
ESSENCE, TIMI IIB, SYNERGY, OASIS 5, ACUTE II, INTERACT, A to Z
Fondaparinux:
OASIS 5
Bivalirudin:
ACUITY
Plavix:
CURE
GPIIb/IIIa Inhibitor:
ISAR REACT-2 (abciximab), PURSUIT (ebtifbatide), PRISM PLUS (tirofiban)
www.
Clinical trial results.org
Anticoagulants and Antiplatelets – Initial Conservative Strategy Recommendation Evidence
Enoxaparin, UFH, (I, A) or Fondaparinux (I, B) ASAP Fondaparinux if increased bleeding risk (I, B)
Plavix
(loading dose plus maintainence) ASAP, continued for 1 month, ideally up to 1 year (I, A)
etifibatide or tirofiban
addition to Plavix (IIb, B), but not abciximab (IIIA) in
www.
Clinical trial results.org
Enoxaparin:
TIMI 11B, A to Z, INTERACT ESSENCE,
Fondaparinux:
OASIS 5 CURE ARMYDA 2
Important Points in Hospital Care
• Stress test before discharge for assessment of ischemia in initial conservative strategy. Must be free of resting ischemia or HF for 12-24h – Class I, C • If not classified as low risk, angiography should be performed – Class I, A • Fasting lipid panel within 24 hours – Class I, C • Statin regardless of baseline LDL-C pre-discharge • Echo or MUGA must be done if no plan for left ventriculography by angiogram – Class I, B
www.
Clinical trial results.org
Acute Coronary Syndromes
•
Pathophysiology
•
Diagnosis
•
Triage
•
Initial Therapy
•
Invasive vs Conservative
• Post AMI Care
www.
Clinical trial results.org
Post-AMI Care
• Similar to care after STEMI • Focus on secondary prevention of coronary events… – ASA – – – – – Statin BB BP control Smoking Cessation Healthy Lifestyle • …And treatment of LV systolic Dysfunction (EF<40) – ACE inhibitor – – ARB if ACE inhibitor intolerant Eplerenone if HF or DM, and eGFR > 30, and K < 5
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Clinical trial results.org
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When to Stop Plavix