Objectives Acute Coronary Syndromes; The Nuts and Bolts Michael P. Gulseth, Pharm. D., BCPS Pharmacotherapy II Spring 2006 Compare and contrast pathophysiology of unstable angina (UA), non-st segment elevation MI (NSTEMI), and ST segment elevation MI (STEMI) Identify how the specific diagnosis of MI is made Identify high risk markers in patients with UA or NSTEMI List the two reperfusion strategies used to treat patients with STEMI List the two reperfusion strategies usually employed early for high risk UA or NSTEMI patients Overview Cardiovascular disease (CVD) is the #1 killer of Americans The most common cause of CVD death are the acute coronary syndromes Every year 1 million Americans will experience ACS; 239,000 will die of an MI The cause of ACS is the rupture of a atherosclerotic plaque and subsequent activation of platelets and the clotting cascade Quick quiz.. Based on the little we have just talked about, what would be logical medication choices to treat these patients? Any guesses as to risk factors of developing these plaques? Hypertension Male gender Tobacco use DM Obesity Elevated homocysteine Dyslipidemia How dose the plaque start? The earliest stage is called endothelial dysfunction Starts early in life and characterized by: Imbalance between vasocontricting and vasodilating substances leading to vascular reactivity Imbalance of procoagulant and anticoagulant molecules; promotes platelet aggregation and thrombus formation Increase expression of leukocyte adhesion molecules that attract inflammatory cells in the vessel wall Permeability to LDL cholesterol and inflammatory cells is increased and deposit in the subintimal vessel wall Leads to fatty streaks and eventual plaque formation 1
Foam Cells From First Decade Atherosclerosis Timeline Fatty Streak Intermediate Lesion Atheroma Fibrous Complicated Lesion/ Plaque Rupture Endothelial Dysfunction From Third Decade From Fourth Decade ACS Spectrum ACS is catch all of conditions that lead to acute myocardial ischemia From an imbalance between myocardial O 2 supply and demand Due to an occlusive or partially occlusive coronary artery thrombus due to a plaque rupture ACS is categorized via the ECG changes seen NSTEMI is different than UA in that the ischemia was bad enough to cause necrosis leading to myocite release of biochemical markers like troponin and creatine kinase Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 104). Spectrum of Acute Coronary Syndrome Ischemic Discomfort Unstable Symptoms History Physical Exam No ST-segment elevation ST-segment elevation ECG (10 min) Unstable NSTEMI STEMI Angina (Non-Q MI) (Q-wave MI) (positive cardiac biomarker) Cardiac Biomarkers STEMI ECG NSTEMI ECG A. Normal ECG prior to MI B. Hyperacute T wave changes increased T wave amplitude and width; may also see ST elevation C. Marked ST elevation with hyperacute T wave changes (transmural injury) D. Pathologic Q waves, less ST elevation, terminal T wave inversion (necrosis) (Pathologic Q waves are usually defined as duration >0.04 s or >25% of R-wave amplitude) E. Pathologic Q waves, T wave inversion (necrosis and fibrosis) F. Pathologic Q waves, upright T waves (fibrosis) 2
Warning Arrhythmias What happens to start an episode of ACS? Begins with rupture, fissuring, or erosion on an unstable plaque Usually plaques of < 50% when this occurs Clots form due to the exposure of collagen and tissue factor Causes platelet adhesion and activation Also activates the clotting cascade Thrombis can be partially or totally occlusive Which ACS condition would result from each of the above? Antman and Rutherford. Coronary Care Medicine. Boston, MA: Martinus Nijhoff Publishing;1986:81. Onset of STEMI - Prehospital issues - Initial recognition and management in the Emergency Department (ED) - Reperfusion Hospital Management - Medications - Arrhythmias - Complications - Preparation for discharge Thrombus Formation Secondary Prevention/ Long-Term Management Management Before STEMI 1 Modified from Libby. Circulation 2001;104:365, Hamm et al. The Lancet 2001;358:1533 and Davies. Heart 2000;83:361. 2 3 4 5 6 4 Presentation Working Dx ECG Cardiac Biomarker Final Dx Ischemic Discomfort Acute Coronary Syndrome No ST Elevation UA ST Elevation Chronology of the interface between the patient and the clinician through the progression of plaque formation and the onset of complications of STEMI. Fibrin Red cells Platelets Plaque rupture NSTEMI Unstable Angina NQMI QwMI Myocardial Infarction 3
Now, about those clots.. Thrombus that have more platelets than fibrin have a white appearance White clots More common in UA and NTEMI Myocardial ischemia also occurs due to downstream embolism of microthrombi STEMI patients have a completely occluded lumen and contain much more fibrin and red blood cells and smaller amounts of platelets Red clot Ventricular Remodeling Occurs in some cardiovascular conditions Heart failure MI Left ventricle changes in size, shape, and function Leads to heart failure Want to prevent this Caused by upregulation of the renin-angiotensin-aldosterone system (RAS), sympathetic nervous system, other hemodynamic factors, mechanical factors, changes in gene expression All of this promotes both systolic and diastolic dysfuntion Based on the upregulation of the RAS and sympathetic nervous system, what agents could help prevent this process? What are the complications of MI? Presentation Cardiogenic shock Heart failure Valvular dysfunction Ventricular and atrial arrhythmias Bradycardia Heart block Pericarditis Stroke due to left ventricle thrombus embolization Venous thromboembolism Left ventricle rupture See Table 16-1 in your text ECG needs to be obtained to risk stratify the ACS being experienced Usually compared to an old ECG Looking for ST-elevation or depression, T wave inversion Depending on leads and where changes are see, this can help identify which artery is involved 4
Biochemical Markers Biochemical markers are used to confirm the diagnosis of MI Released when myocardial cells die Blood is obtained three times over 12-24 hours Need at least one positive troponins or two positive CK MB to confirm diagnosis of MI Troponins stay elevated for up to 10 days Risk Stratification Patient symptoms, past medication history, ECG, and biochemical markers are used together to stratify risk for each patient Since complete occlusion, STEMI patients require immediate revascularization Done with lytics or a primary PCI Lytics should be given within 30 minutes of presentation Balloon inflation with primary PCI must occur within 90 minutes The sooner the better Risk Stratification for UA/NSTEMI Not the same type of emergency that STEMI is TIMI risk scoring is useful for these patients TIMI Risk Low Risk 0-2 points Medium Risk 3-4 points High Risk 5-7 points TIMI is not always used in actual practice to define risk, however, it gives a students a good idea who is higher risk UA/NSTEMI Treatment/Low Risk Evaluated in the ER with serial biochemical markers If negative, usually admitted to the floor with telemetry and may undergo a stress test 5
UA/NSTEMI Treatment Medium-High Risk Admitted to hospital; could go to coronary intensive care, chest pain unit, or general floor based on perceived risk High risk patient will also undergo early PCI and revascularization if stenosis is found Moderate risk patients with MI will also typically go for PCI and revascularization during hospital stay Moderate risk patients without MI may have a stress test before PCI Much of the pharmacotherapy is dictated by risk stratification and the plan of action Other General Treatments of ACS All STEMI and medium to high risk NSTEMI patients get: Admitted to hospital O 2 if saturations are low Continuous telemetry monitoring Frequent vital sign checks Best rest for 12 hours Stool softeners Pain relief Revascularization STEMI Primary PCI in 90 minutes (preferred) or if lytics contraindicated Lytics UA/NSTEMI PCI CABG These are usually within 24 hours for medium to high risk patients PCI with stent Catheter is inserted in groin in femoral artery Catheter is threaded to aorta dye is infused into the heart chambers Lights up the coronary arteries on X-ray and lesions can be detected Problem lesions are then stented Fibrinolytics Are simply boring drugs Clot busters Activate plasminogen to plasmin Artery is taken from your chest or leg Internal mammary Saphenous Radial One end is attached to the aorta and the other to a point below the clog CABG 6
Conclusion ACS results from clot formation on a ruptured coronary artery STEMI results when the coronary artery is completely occluded UA/NSTEMI result when the occlusion in incomplete The MI diagnosis is confirmed by positive biochemical markers TIMI risk stratification can be helpful to risk stratify UA/NSTEMI patients STEMI patients must be quickly revascularized with primary PCI or lytic therapy Medium to high risk UA or NSTEMI patients typically undergo PCI or CABG Review Questions What event starts on episode of ACS? In a NSTEMI event, is the occlusion complete or partial? STEMI? What diagnostic markers are used to diagnose an MI? What are high risk markers in patients with UA/NSTEMI, and how does this relate to therapy? What are the two general reperfusion strategies employed in UA/STEMI? STEMI? 7