Updates on acute coronary syndrome

1. Updates on acute coronary syndrome Dr. Eric Yeung Mar 2008

2. Acute coronary syndrome:The spectrum • Unstable angina (UA) • Non-ST elevation myocardial infarction (NSTEMI) • Closely related, different severity, myocardial injury • ST-elevation myocardial infarction (STEMI)

5. Case scenario • M/58. • Lifelong non-smoker, non-drinker. • Good past health, insignificant family history. • Regular daily swimming exercise.

6. Case scenario • Sudden transient central chest pain ~ 2 hours after swimming. • No previous history of exertional angina. • No diaphoresis / shortness of breath. • No radiation but transient LUL weakness. • Resolve after 1 hour but still with vague chest discomfort.

7. Physical examination • Largely unremarkable. • Not in distress. • Clinically not in heart failure. • HS Dual, no murmur.

8. What would you do?

9. Symptoms recognition… by patient • Typical vs atypical • “It’s not chest pain” • “It won’t be me” • “It’s a chronic problem” • “It’s going to resolve soon” • Silent and unrecognized events. • Older • Women • DM • Prior HF

10. Symptoms recognition… by doctors • History taking. • Typical vs atypical. • Tempo / progression. • Presence of risk factors. • Use of TNG / GI medications with pain relief? • Physical examination. • Investigations. • 12-lead electrocardiogram. • Cardiac biomarkers of necrosis.

11. Investigation • CXR: Clear lung fields. • 1st set of cardiac enzymes: CK normal. TnI normal. • 12-lead ECG

13. What is your next step? • Discharge the patient. • Admit the patient and observe. • Admit the patient and start aspirin. • Admit the patient and start LMWH. • Admit the patient and start streptokinase. • Admit the patient and call cardiac on-call for primary PTCA.

14. Electrocardiogram • Transient ST segment changes during symptomatic episode at rest strongly suggest acute ischaemia. • ST depression. • T inversion, especially if marked (>2mm) • Q waves: prior MI. • Normal ECG does not exclude ACS. • 4% MI with isolated posterior chest leads ST elevation (V7-9) • Serial / continuous monitoring increases yield.

15. Cardiac markers • Myoglobin. • Found in both cardiac and skeletal muscle. • Rapid release (< 2h) after onset of necrosis. • More useful in rapidly ruling out MI.

16. Cardiac markers • CK-MB • Less sensitive and specific for MI than troponins. • Shorter half-life, allows detection of secondary increases in levels. • Useful for diagnosis of early infarct extension.

17. Cardiac markers • Troponins: Subunits T and I. • High concentrations in myocardium. • Level rise maybe delayed up to 8-12 hours. • Persist for 5-14 days. • Less specific in renal dysfunction but retains predictive ability.

18. Trend of cardiac markers

19. Back to the case • Admitted for close observation. • ECG repeated: no interval change. • 2nd set of cardiac markers: Both CK and TnI markedly raised. • Started medical therapy. • Coro: dLAD 70% stenosis. Cypher stent inserted, uneventful.

20. Case illustration • Careful history. • Absence of common risk factors does not mean ACS is impossible. • Atypical symptoms. • Importance of serial monitoring.

21. Other newer imaging • Cardiac MRI • Coronary CT angiography

22. Newer imaging • CT coronary angiography

23. CT coronary angiography • Hard plaque

24. CT coronary angiography • Soft plaque

25. CT coronary angiography • Stent in-situ with stenosis just proximal to stent

26. Newer imaging • Cardiac MRI + stress test

27. Management • Relief of ischaemia • Prevent serious adverse outcomes • Anti-ischaemic • Aspirin / beta-blocker / clopidogrel / GP IIb/IIIa antagonist • Anti-coagulant • Invasive procedures

28. General care • Bed rest • Initial routine oxygen + subsequent supplementary oxygen. • Cardiac monitoring.

29. Nitrates • Both peripheral and coronary vasodilator • Reduce myocardial oxygen demand • Enhance myocardial oxygen delivery • Promotes collateral flow and redistribution to ischaemic regions • Monitor systolic BP • Avoid in hypotension / bradycardia / tachycardia. • Convert to non-parenteral alternative < 24hrs.

30. Morphine • Pain not relieved with nitrates or recurrent pain. • SE: Hypotension, GI upset, respiratory depression • Observational registry (Meine et al., 2005): Higher adjusted likelihood of death with morphine use in UA / NSTEMI.

31. Beta-blockers • Block effects of catecholamines on beta-receptors. • Early IV use not beneficial. • Recommended orally within 1st 24 hours of UA/NSTEMI. • For secondary prevention as well.

32. Calcium channel blockers • Greatest benefit: Verapamil and diltiazem. • Decreased myocardial oxygen demand • Improved myocardial flow. • SE: Hypotension, worsening HF, bradycardia, AVB. • For patients unresponsive to nitrates / beta-blockers. • Avoid in pulmonary oedema / severe LV dysfunction. • Caution with beta-blockers: synergistically depress LV function / sinus and AV node conduction.

33. Inhibitors of RAAS • ACEI reduce mortality in AMI / recent MI with LV systolic dysfunction / DM with LV dysfunction / high risk for CAD. • ARB: If intolerance to ACEI. • Eplerenone (Selective aldosterone receptor blocker): Reduce mortality in MI with LV dysfunction • Spironolactone: Decrease morbidity and death with severe HF.

34. Intra-aortic balloon counterpulsation • Used for > 30 years. • Refractory UA after MI. • Cardiogenic shock. • Haemodynamic support during catheterization / angioplasty. • Mechanical complications of MI. • Limited randomized data.

35. NSAIDs / COX-2 selective inhibitors • Increased cardiovascular events. • To be avoided. • Should be discontinued.

36. Aspirin

37. Aspirin • Consistent benefit documented over placebo. • 75mg to 1500mg: similar reduction in odds of vascular events. • Dose-dependent increase in bleeding. • Recommended: 75 to 162mg daily, initiated ASAP and continued indefinitely. • Better buccal absorption with non-EC formula. • Consider increase dose to 162-325mg daily after PTCS.

38. Thienopyridines • Adenosine diphosphate receptor antagonists. • Ticlopidine and clopidogrel. • Irreversible platelet antagonists. • Take several days for maximal effect. • Ticlopidine: neutropenia, TTP.

39. Clopidogrel • Extensive clinical testing. • CAPRIE trial: At least as effective as or modestly more effective than aspirin. • CURE trial: • Reduced cardiovascular death, MI, stroke when given with aspirin (9.3% vs 11.5% in placebo, RR 0.80, p<0.001) • Reduced in-hospital ischaemia and revascularization. • Small increase in bleeding risk.

40. Clopidogrel • PCI-CURE: Substudy of PCI within CURE. • Reduced cardiovascular death / MI / urgent target vessel revascularization by 30% (p=0.03) • Reduced cardiovascular death or MI by 31% (p=0.002) • Optimal timing of loading dose not certain.

41. Clopidogrel • Greatest benefit in 1-3 months. • Favourable results observed over 1 year. • Pathological and clinical evidence suggests need of longer-term therapy in DES. • Not beneficial as primary prevention, even in high risk groups.

42. Other choices • Not beneficial: • Sulfinpyrazone • Dipyridamole • Prostacyclin • Prostacyclin analogs • Thromboxane synthase blockers / thromboxane A receptor antagonists: Not superior over aspirin.

43. Anticoagulants • Unfractionated heparin • Enoxaparin • Bivalirudin • Fondaparinux • All effective but none documented superiority • Different study designs • ? Equipotent dosing. • Different patient populations. • Different duration of therapy.

44. UFH • Accelerates action of circulating anti-thrombin. • Inactivates factor IIa / Ixa / Xa. • Prevents thrombus propagation but does not lyse existing thrombi. • Reduction of 33-56% (p=0.06 to 0.03) in early ischaemic events.

45. UFH: Disadvantages • Short-term benefit, “rebound” after discontinuation. • Heavily bound: plasma proteins, blood cells, endothelial cells. • Poor bioavailability, marked variability in anticoagulation. • Possibility of heparin-induced thrombocytopenia. • aPTT and CBC monitoring.

46. LMWH • Inactivate both thrombin and factor Xa • Less binding, longer half-life. • More predictable and sustained anticoagulation. • Less HIT. • Subcutaneous administration. • No need for monitoring. • No prolonged benefits beyond acute phase.

47. LMWH • Favourable results when comparing LMWH with ASA vs ASA alone. • Minimal prolonged benefits beyond acute phase. • Previous trials: • Dalteparin / nadroparin: Similar to UFH. • Enoxaparin: More favourable than UFH. OR 0.91. (Death and non-fatal MI) • EVET: Enoxaparin has lower rate of death / MI / recurrent angina at 7 and 30 days than tinzaparin.

48. Direct thrombin inhibitors • Hirudin as prototype. • Bivalirudin: Synthetic analog of hirudin. • Reversible bining to thrombin. • Inhibits clot-bound thrombin. • ACUITY trial: Non-inferior 30-day rates of ischaemia, major bleeding, and net clinical outcomes with heparin.

49. Fondaparinux • Factor Xa inhibitor. • Inhibit multiplier effects of downstream reaction, suppressing thrombin generation. • Similar advantages of LMWH. • No action on preformed thrombin.

50. Fondaparinux • OASIS-5: Non-inferiority compared with enoxaparin (Death / MI / refractory ischaemia) at 9 days with less major bleeding. • Lower event rates (Death / MI / stroke) at 6 months. • OASIS-6: More catheter thrombosis during angiography / PCI. • Recommended with UFH during PCI.