Unstable Angina and Non-ST elevation Myocardial Infarction

1. Unstable Angina and Non-ST elevation Myocardial Infarction John Blair, MD

2. Unstable Angina / Non ST-Elevation Myocardial Infarction (UA/NSTEMI) • Pathophysiology • Diagnosis • Initial Therapy • Risk-Stratification • Invasive vs Conservative • Post AMI Care

3. UA / NSTEMI • Pathophysiology • Diagnosis • Initial Therapy • Risk-Stratification • Invasive vs Conservative • Post AMI Care

4. Sudden Thrombus or Thromboembolism Superficial Erosion Ruptured Fibrous Cap Modified from Libby PCirc 104:365,2001

5. Hamm Lancet 358:1533,2001 Ischemic Discomfort Presentation Acute Coronary Syndrome Working Dx Davies MJ Heart 83:361, 2000 No ST Elevation ST Elevation ECG NSTEMI Biochem. Marker Myocardial Infarction Unstable Angina NQMI Qw MI Final Dx

6. 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.

7. Acute Coronary Syndromes • Pathophysiology • Diagnosis • Initial Therapy • Risk-Stratification • Invasive vs Conservative • Post AMI Care

8. Likelihood that Signs and Symptoms Represent ACS Braunwald E, Mark DB, Jones RH NHLBI Unstable Angina 1994

9. Algorithm for Evaluation and Management of Patients Suspected of Having ACS Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157

10. Timing of Release of Various Biomarkers After Acute Myocardial Infarction Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157

11. Acute Coronary Syndromes • Pathophysiology • Diagnosis • Initial Therapy • Risk-Stratification • Invasive vs Conservative • Post AMI Care

12. Treatment • Increases oxygen supply to ischemic tissue • Start at 4L/min • Use caution in COPD patients • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins

13. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • Blocks formation of thromboxane A2 and thus prevents platelet aggregation • Reduces mortality, reinfarction, and stroke in patients with MIs

14. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • Blocks catecholamines from binding to β-adrenergic receptors • Reduces myocardial demand by reducing HR, BP, contractility • Decreases incidence of primary VF

15. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • Dilates coronary arteries • Increases venous dilation and therefore decreases venous return • Decreases myocardial demand by decreasing preload

16. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • Reduces pain of ischemia and anxiety  indirect effect on catecholamines • May dilate coronary arteries and reduce preload  decreases myocardial oxygen demand

17. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • Heparins - Indirect thrombin inhibitors including LMWH • DTI - Direct thrombin inhibitors • Reduce further coagulation

18. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • Blocks platelet receptor so platelets cannot bind fibrinogen and form clots • caution in renal disease (tirofiban, ebtifbatide) and with thrombocytopenia (abciximab)

19. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • 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

20. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • reduces peripheral vasoconstriction and blood pressure • Alters post-MI LV remodeling

21. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • reduces fibrosis, hypokalemia, and arrhythmias • beneficial in high-risk post-AMI LV dysfunction

22. Treatment • Oxygen • Aspirin • Beta-blocker • Nitroglycerin • Morphine • Heparins, DTIs • IIb/IIIa inhibitors • Plavix • ACE/ARB • Aldosterone Blockade • Statins • reduce LDL • may decrease inflammation

23. Initial Therapy • Anti-ischemic and Analgesic therapy • Anti-platelet therapy • Anti-coagulant therapy

24. ACC/AHA Guidelines – Updated in 2007 from 2002

25. 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

26. Anti-ischemic and Analgesic Therapy • 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

27. Anti-Platelet Therapy • 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

28. Anti-Coagulant Therapy • Anticoagulant Therapy should be added to antiplatelet therapy as soon as possible after presentation • Choice of anticoagulant depends on the strategy chosen (more on this later)

29. There is an Incremental Benefit to ASA, UFH/LMWH, and GPIIb/IIIa Therapy Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157

30. Acute Coronary Syndromes • Pathophysiology • Diagnosis • Initial Therapy • Risk-Stratification • Invasive vs Conservative • Post AMI Care

31. Kaplan-Meier Estimates of Probability of Death Based on Admission Electrocardiogram Savonitto S, Ardissino D, Granger CB, et al. JAMA 1999;281:707–13 (127)

32. 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)

33. TIMI Risk Score – Cardiac Events by 14 Days(TIMI 11B, ESSENCE)

34. 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)

35. What is Elevated Risk? Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157

36. Acute Coronary Syndromes • Pathophysiology • Diagnosis • Initial Therapy • Risk-Stratification • Invasive vs Conservative • Post AMI Care

37. 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 angiography (ISAR-COOL) or • Deferred Angiography (all other trials – 12-48h)

38. 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

39. Less Events in Early Invasive Strategy Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157

40. 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)

41. Anticoagulants and Antiplatelets – Initial Invasive Strategy

42. Anticoagulants and Antiplatelets – Initial Conservative Strategy

43. 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

44. Acute Coronary Syndromes • Pathophysiology • Diagnosis • Triage • Initial Therapy • Invasive vs Conservative • Post AMI Care

45. 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

46. When to Stop Plavix Anderson, J. L. et al. J Am Coll Cardiol 2007;50:e1-e157

47. Thank You