Acute Coronary Syndrome (cont)

b]Emergency Department Care[/b]
The ACS spectrum concept is a useful framework for developing therapeutic strategies. Antithrombin therapy and antiplatelet therapy should be administered to all patients with an ACS regardless of the presence or the absence of ST-segment elevation. Patients presenting with persistent ST-segment elevation are candidates for reperfusion therapy (either pharmacological or catheter based) to restore flow promptly in the occluded epicardial infarct-related artery. Patients presenting without ST-segment elevation are not candidates for immediate pharmacological reperfusion but should receive anti-ischemic therapy and PCI when appropriate. "Time is myocardium" is a dictum to be remembered as survival has been shown to correlate with time to reperfusion in patients with acute MI. Many centers set goals for, and routinely record, door-to-ECG, door-to-needle (thrombolytic therapy), or door-to-vascular access (for patients receiving PCI) times as measures of quality of care provided.
• Goals of ED care are rapid identification of patients with STEMI, exclusion of alternative causes of nonischemic chest pain, and stratification of patients with acute coronary ischemia into low- and high-risk groups.
• Obtain intravenous access, administer supplemental oxygen, and provide telemetry monitoring if these procedures have not already been accomplished in the prehospital phase. In addition, obtain a 12-lead ECG as soon as possible after arrival.
• Complete a history and physical examination, with focus on risk factors for coronary ischemia; onset, duration, and pattern of symptoms; and early identification of complications of myocardial ischemia (eg, new murmurs, CHF).
• Perform frequent reassessment of vital signs and symptoms in response to administered therapies.
• Serial ECGs and continuous ST-segment monitoring may be useful.
• Many EDs have an observation unit that may be an appropriate disposition for patients who meet admission criteria.
• Medical therapy, as discussed in Medication, is indicated.
Consultations
Cardiology or interventional cardiology consultation may be indicated for patients with any of the following:
• STEMI - Depending on the center, the patient may be a candidate for PCI, and immediate interventional cardiology consultation is indicated.
•
o Ongoing symptoms highly suggestive of acute coronary ischemia and nondiagnostic ECG (eg, left bundle-branch block [LBBB])
o Ongoing symptoms refractory to aggressive medical therapy
o Hemodynamic instability
o Evidence of acute valvular dysfunction
o Shock
o Known severe aortic stenosis and ongoing symptoms
o Uncertainty of the diagnosis

The goals of treatment are to preserve patency of the coronary artery, augment blood flow through stenotic lesions, and reduce myocardial oxygen demand. All patients should receive antiplatelet agents, and patients with evidence of ongoing ischemia should receive aggressive medical intervention until signs of ischemia, as determined by symptoms and ECG, resolve.
Drug Category: Antiplatelet agents
These agents inhibit the cyclooxygenase system, decreasing the level of thromboxane A2, which is a potent platelet activator. Antiplatelet therapy has been shown to reduce mortality rates by reducing the risk of fatal strokes and fatal myocardial infarctions.
Drug Category: Nitrates
These agents oppose coronary artery spasm and reduce myocardial oxygen demand by reducing both preload and afterload.
Drug Category: Analgesics
These agents reduce pain, which decreases sympathetic stress, in addition to providing some preload reduction.Drug Category: Anticoagulants
These agents are used to prevent recurrence of clot after a spontaneous fibrinolysis.
Drug Category: Beta-adrenergic blockers
These agents have antiarrhythmic and antihypertensive properties as well as ability to reduce ischemia. They minimize the imbalance between myocardial supply and demand by reducing afterload and wall stress. In patients with acute MI, they have been shown to decrease infarct size as well as short- and long-term mortality, which is a function of their anti-ischemic and antiarrhythmic properties.
Drug Category: Glycoprotein IIB/IIA inhibitors
Glycoprotein (GP) IIb/IIIa antagonists prevent the binding of fibrinogen, thereby blocking platelet aggregation. Studies to date suggest that as a class, the addition of intravenous GP IIb/IIIa inhibitors to aspirin and heparin improves both early and late outcomes, including mortality, Q-wave MI, need for revascularization procedures, and length of hospital stay.
Currently, IIb/IIIb antagonists in combination with aspirin are considered standard antiplatelet therapy for patients at high risk for unstable angina. Adenosine diphosphate (ADP) antagonists are not considered standard therapy but may be used in patients unable to tolerate aspirin.
Drug Category: Low molecular weight heparins
Low molecular weight heparin (enoxaparin) has been shown to reduce cardiac ischemic events and death by as much as 15% in patients with unstable angina. The benefits appear to be sustained at 1 year, with a 13% reduction in patients requiring coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) and a 15% reduction in death or AMI. These clinical effects have been reported with all patients also receiving aspirin.
One systematic review comparing low molecular weight heparin (LMWH) with unfractionated heparin found no significant difference in benefits between the two. The advantages of using LMWH over unfractionated heparin are ease of administration, absence of need for anticoagulation monitoring, safety profile, and potential for overall cost savings. Although 3 LMWHs are approved for use in the United States, only enoxaparin is currently approved for use in unstable angina. Lev et al found that the combination of eptifibatide with enoxaparin appears to have a more potent antithrombotic effect than that of eptifibatide and unfractionated heparin (UFH).3
Drug Category: Direct thrombin inhibitors
Hirudin is the prototype of direct thrombin inhibitors. Hirudin binds directly to the anion binding site and the catalytic sites of thrombin to produce potent and predictable anticoagulation.
Drug Category: Adenosine diphosphate receptor antagonists
Two thienopyridines, clopidogrel and ticlopidine, are ADP antagonists that are approved for antiplatelet activity. Both have irreversible antiplatelet activity but take several days to manifest. A potential additive benefit exists when ADP antagonists are used in conjunction with aspirin.
These drugs may be considered alternatives to aspirin in patients intolerant or allergic to aspirin.
Further Inpatient Care
• Patients with unstable angina, ECG changes, or both should be admitted to a telemetry bed. A certain subset of patients with stable angina may be treated as outpatients with antianginal agents, but close follow-up is necessary.
• Patients with symptoms refractory to aggressive medical treatment, shock, suspected or known aortic stenosis, or new or worsening mitral regurgitation are at high risk. Management for these patients should include the following:
•
o Admission to an intensive care unit setting
o Cardiology consultation
• Intra-aortic balloon pump (IABP) and early angiography to delineate anatomy should be considered.
• Antiplatelet and antianginal medications initiated in the ED should be continued. Subsequent dosing is determined by symptomatic response and tolerance of side effects.
• The routine use of lidocaine as prophylaxis for ventricular arrhythmias in patients with ACS is not indicated. In MI, it has been shown to increase mortality rates. Lidocaine may be used for patients with complex ventricular ectopy or for patients with hemodynamically significant, nonsustained, or sustained ventricular tachycardia.
Further Outpatient Care
• Patients with chronic stable angina may be considered for discharge after occurrence of the following:
•
o Symptom duration is brief and identical to symptoms experienced in the past.
o ECG is normal or unchanged.
o Patient has access to timely follow-up with a primary care physician.
• When in doubt, admit. The usual reason for a patient with chronic stable angina to present to the ED is a change in pattern or severity of symptoms, which makes their angina unstable.
• A study by Bartholomew et al may be helpful in making the decision to admit or discharge. This prospective thrombolysis in myocardial infarction risk score (TIMI-RS) used 7 variables in patients with suspected ACS: (1) age older than 65 years, (2) 3 or more cardiac risk factors, (3) ST deviation, (4) aspirin use within 7 days, (5) 2 or more anginal events over 24 hours, (6) history of coronary stenosis, and (7) elevated troponin levels. Patients were contacted at 30 days, and data were collected concerning major adverse cardiac events.4
•
o In patients presenting with chest pain, a higher TIMI-RS was associated with an increase in major adverse cardiac events within 30 days. The authors concluded that the 30-day event rate was 0% for a score of 1, 20% for a score of 2, 24% for a score of 3, 42% for a score of 4, 52% for a score of 5, and 70% for a score of 6 or 7 (p < 0.0001).
o The TIMI-RS successfully differentiates early risk for major adverse cardiac events in a general population presenting with symptoms suggestive of ACS. A simple bedside calculation of the TIMI-RS provides rapid risk stratification, allowing facilitation of therapeutic decision-making in patients with symptoms suggestive of ACS and may be helpful with the patient's disposition.
In/Out Patient Meds
• Aspirin
• Use clopidogrel as a substitute for patients unable to take aspirin because of a history of hypersensitivity or bleeding. Use a 300-mg loading dose, then 75 mg qd.
• Nitrates
•
o Use topical or oral nitrates for those who are discharged or for those who are stable inpatients.
o Intravenous infusion is preferable for those admitted with unstable symptoms.
• Beta-blockers
•
o Metoprolol and propranolol are excellent choices for inpatient and outpatient management.
o Use esmolol for inpatient treatment, particularly those at risk for adverse effects from beta-blockade.
• Heparin: Use heparin for inpatient management of unstable angina. Some preliminary data suggest that LMWH is a safe and effective alternative.
• Significant clustering of recurrent ischemic events occurs within 24 hours after cessation of both short-term UFH and enoxaparin treatment, and patients should be carefully monitored during that period. This early rebound may be prevented by continuation of a fixed dose of enoxaparin.
Transfer
• Consider transfer only for patients at particularly high risk and for those who are being evaluated in a center without access to timely cardiac catheterization, PTCA, or bypass.
• High-risk criteria include the following:
•
o Symptoms refractory to medical management
o Hemodynamic instability, cardiogenic shock
o New or worsening mitral regurgitant murmur
o Known or suspected severe aortic stenosis
• The risks of transferring these unstable patients must be carefully weighed against the benefits of transfer.
Deterrence/Prevention
• Cessation of smoking
• Assessment of lipid profile and dietary changes, where appropriate (Among patients who have recently had an ACS, an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than a standard regimen.5)
• Blood pressure control
• Compliance with medications, particularly aspirin
• Comprehensive risk assessment by primary care physician, including exercise tolerance test (ETT) for individuals at high risk and identification of structural heart disease (eg, left ventricular hypertrophy [LVH], aortic stenosis)
Complications
• Acute myocardial infarction
• Cardiogenic shock
• Ischemic mitral regurgitation
• Arrhythmias
•
o Supraventricular arrhythmias (rare complication of ischemia, may actually precipitate ischemic events)
o Ventricular arrhythmias; simple and complex premature ventricular contractions (PVCs), and nonsustained ventricular tachycardia (NSVT)
• Atrioventricular nodal blockade
•
o Usually transient in setting of reversible ischemia
o Treatment guided by location of block and hemodynamic stability
• Ventricular rupture occurs in the interventricular septum or the LV free wall. This represents a catastrophic event with mortality rates greater than 90%. Prompt recognition, stabilization, and surgical repair are crucial to any hope of survival. An echocardiogram will usually define the abnormality, and a right heart catheterization may show an oxygenation increase with septal rupture.
Prognosis
• Patients with angina either proceed to infarct or have their disease stabilized by medical and/or interventional therapies. Patients with angina are a heterogeneous group; therefore, prognosis varies with respect to stability of disease, demographics, comorbidity, and current intervention.
• Patients with ACS with atrial fibrillation (AF) are associated with increased morbidity and mortality.6
• Patients with ACS and diabetes mellitus, especially those with ST elevation, had increased in-hospital mortality rates. Among patients with ACS and diabetes mellitus, those receiving insulin had worse outcomes. Outcomes were similar for those on hypoglycemic medication or on diet alone.7
• In chronic stable angina, prognosis is generally excellent. Factors that have been shown to impact prognosis include the following:
•
o Aspirin reduces progression to both nonfatal MI and cardiac death.
o Beta-blockers control anginal symptoms and reduce cardiac complications in patients with hypertension.
o PTCA and revascularization improve the prognosis in high-risk patients.
o Poor prognostic factors include male sex, diabetes, and hypertension.
• In unstable angina, prognosis is determined by the ability to control symptoms acutely, preventing progression to AMI. Factors associated with a poorer prognosis include the following:
•
o Evidence of myocardial necrosis, as determined by elevated troponin T level
o Delays in angiography in patients at high risk (Early angiography allows for triage to medical therapy, PTCA, or revascularization.)