Acute Coronary Syndrome

1. Acute Coronary Syndrome Muhammad Asim Rana MRCP(UK)

2. Worldwide Statistics Each year: • > 4 million patients are admitted with unstable angina and acute MI • > 900,000 patients undergo PTCA with or without stent

3. Myocardial Ischemia • Spectrum of presentation • silent ischemia • exertion-induced angina • unstable angina • acute myocardial infarction STEMI NSTEMI

4. Cumulative 6-month mortality from ischemic heart disease 25 N = 21,761; 1985-1992 Diagnosis on adm to hosp 20 15 Deaths / 100 pts / month Acute MIUnstable anginaStable angina 10 5 0 0 1 2 3 4 5 6 Months after hospital admission Duke Cardiovascular Database

5. Percentage of deaths from heart disease

6. Myocardial infarction remains a major cause of death despite contemporary therapeutic strategies. • Diagnosis in the intensive care unit is challenging, but is essential to target therapy accurately. • In patients admitted to the intensive care unit, myocardial infarction is observed to occur frequently, often without being clinically apparent, with a high associated mortality.

7. Myocardial infarction (MI) in the critically ill presents a diagnostic challenge to the physician and is associated with a particularly adverse outcome for the patient. • Such patients have high metabolic demands and are often subject to sustained adverse physiology. • Typical signs and symptoms can be difficult to elicit and surrogate physiological markers of impaired coronary perfusion masked or misinterpreted in the context of the index pathology.

8. Cardiac troponin measurements and the 12-lead echocardiogram (ECG) remain sensitive in this setting, but specificity decreases, resulting in diagnostic uncertainty. • Recent consensus guidelines from the European Society of Cardiology, American College of Cardiology Foundation, American Heart Association and World Heart Federation emphasise the role of cardiac biomarkers in defining MI.

9. Diagnosis requires a rise and/or fall in serum levels (preferably troponin) together with evidence of myocardial ischaemia defined: clinically by patient history; electrocardiographically (new ST-T wave changes, new left bundle branch block or evolving pathological Q waves); or by imaging evidence of new regional wall motion abnormality.

10. Acute Coronary Syndrome • Definition The term ACS refers to a spectrum of presentations caused by myocardial ischemia that includes Unstable Angina Non ST elevation myocardial infarction ST elevation myocardial infarction

11. Ischemic Heart DiseaseEvaluation • Based on the patient’s • History / Physical exam • Electrocardiogram • Biochemical markers • Patients are categorized into 3 groups • Non-cardiac chest pain • Unstable angina • Myocardial infarction (STEMI,NSTEMI)

12. Acute Coronary Syndrome The embracing term reflects the common pathophysiology of plaque disruption Intravascular thrombosis and Impaired myocardial blood supply

13. STEMI is the result of complete epicardial occlusion following plaque disruption & leads to propagation of thrombus & epicardial vasoconstriction • NSTEMI is incomplete & transient epicardial occlusion with platelet-rich & phasic distal embolisation

15. Pathophysiology

17. Pathophysiology (cont’d)

18. Pathophysiology (cont’d)

19. Formation of haemostatic plaque

22. Clinical Features Patients with an ACS may complain of a new onset of Exertional chest pain Chest pain at rest or A deterioration of pre-existing angina. However, some patients present with atypical features including Indigestion Pleuritic chest pain or Dyspnoea

23. Diagnosis • ECG • Biochemical Markers The Cardiac Troponin Complex Myoglobin Creatinine-Kinase MB

24. ECG

25. Biochemical markers

32. Unstable AnginaAnti-platelet Therapy • Abciximab (Abciximab is a monoclonal antibody that binds tightly to GP (glycoprotein) IIb/IIIa receptors and has a long half-life) • EPIC Trialeffective in preventing death, MI, and abrupt closure associated with coronary angioplasty

33. Unstable AnginaAnti-platelet Therapy • Abciximab CAPTURE • At 30 days, there was a 29% reduction in the primary composite endpoint of death, MI, or urgent revascularization in the abciximab group Lancet 1997;349:1429-1435

34. Unstable AnginaAnti-platelet Therapy • Tirofiban (Tirofiban is a small non-peptide that rapidly blocks the GPIIb/IIIa receptors and is reversible in 4–6 hours) • PRISM(Platelet Receptor Inhibition for Ischemic Syndrome Management) • 3,200 patients with unstable angina were treated with either heparin or tirofiban • At 48 hours, there was significant risk reduction (5.9% to 3.6%) in the rate of death, MI, or refractory ischemia. N Engl J Med 1998;338:1498-505

35. Unstable AnginaAnti-platelet Therapy • Tirofiban • PRISM -PLUS(Platelet Receptor Inhibition for Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms) • randomized 1,915 patients with UA and non-Q-MI to tirofiban alone, heparin alone, or a combination of the two (all received aspirin) N Engl J Med 1998;338:1488-97

36. Unstable AnginaAnti-platelet Therapy • Eptifibatide (Eptifibatide is a cyclic peptide that selectively inhibits GPIIb/IIIa receptors, but has a short half-life and wears off in 2–4 hours.) • PURSUIT(Platelet IIb/IIIa Underpinning the Receptor for Suppression of Unstable Ischemia Trial) • ~11,000 patients admitted with unstable angina or non-Q-wave myocardial infarction • a broad-based trial encompassing a variety of clinical practices and practice styles NEJM 1998;339:436-443 MedSlides.com

37. Unstable AnginaAnti-platelet Therapy • Eptifibatide PURSUIT • randomized to eptifibatide or placebo; all patients received aspirin and heparin • significantly reduced the risk of death and MI at 30 days from 15.7% to 14.2%, a 9% risk reduction NEJM 1998;339:436-443 MedSlides.com

38. Unstable AnginaAnti-platelet Therapy • Summary • the four “P trials” (PRISM, PRISM-PLUS, PARAGON, PURSUIT) all show reduction of death rate between1.3% and 3.4% - in addition to the benefit of aspirin useful in the management of patients with unstable angina and MI without ST elevation

39. Unstable AnginaAnti-coagulant Therapy • Heparin • recommendation is based on documented efficacy in many trials of moderate size • meta-analyses of six trials showed a 33% risk reduction in MI and death, but with a two fold increase in major bleeding • Titrate PTT to 2x the upper limits of normal 1. Circulation 1994;89:81-88 2. JAMA 1996;276:811-815

40. Unstable AnginaAnti-coagulant Therapy • Low-molecular-weight heparinadvantages over heparin: • better bio-availability • higher ratio (3:1) of anti-Xa to anti-IIa activity • longer anti-Xa activity, avoid rebound • induces less platelet activation • ease of use (subcutaneous - qd or bid) • no need for monitoring

41. ESSENCE Trialincidence of death, MI, or recurrent angina Day 14 Day 30 23.3% 19.8% 19.8% P=0.016 16.6% P=0.019 n=1564 n=1607 n=1564 n=1607 heparin Lovenox heparin Lovenox N Eng J Med 1997;337:447-452

49. What to do?

50. ACS Clinical Diagnosis MONA: Morphine + antiemetic Oxygen Nitrates Aspirin 300 mg stat About 33% of patients with ACS and normal CK (and no ECG changes of infarction) have elevated cTn. Such patients with elevated cTn are, however, four times more likely to suffer further infarction or death in the next 30 days. Blood Tests: Troponin at 12 hours after onset of pain, U&E, cholesterol, FBC, coagulation Admission or subsequent ECG