Introduction
Acute coronary syndromes comprise the spectrum of unstable cardiac ischemia from unstable angina to acute myocardial infarction. Rather than the traditional nomenclature of unstable angina, non-Q wave and Q wave myocardial infarction, acute coronary syndromes are now classified based on the presenting electrocardiogram as either “ST elevation” or “non-ST elevation.” This allows for immediate classification and guides determination of whether patients should be considered for acute reperfusion therapy. The evolution of cardiac markers then allows determination of whether myocardial infarction has occurred. Acute coronary syndromes represent a dynamic state in which patients frequently shift from one category to another, as new ST elevation can develop after presentation and cardiac markers can become abnormal with recurrent ischemic episodes.

Diagnosis
Many patients with acute coronary syndromes will exhibit electrocardiographic changes during pain - either ST segment elevation, ST segment depression, or T wave flattening or inversion. They may exhibit signs of left ventricular dysfunction during pain and for a time thereafter.

Chest pain is one of the most frequent reasons for emergency department visits. Algorithms have been developed to aid in determining the likelihood that a patient has an acute coronary syndrome, and for those patients that do have an acute coronary syndrome, the risk of death or death and ischemic events.

Many hospitals have developed chest pain observation units to provide a systematic approach toward serial risk stratification to improve the triage process. In many cases those who have not experienced new chest pain and have no electrocardiographic changes or cardiac enzyme elevations undergo treadmill exercise tests or imaging procedures to exclude ischemia at the end of an 8- to 24-hour period and are discharged directly from the emergency department if these tests are negative.

Treatment
Table 10-4 provides a summary of the American College of Cardiology/American Heart Association Guideline recommendations for selected medical treatments.

A. General Measures
Treatment of acute coronary syndromes without ST elevation should be multifaceted and vigorous. Patients who are at high risk should be hospitalized, maintained at bed rest or at very limited activity, monitored, and given supplemental oxygen. Sedation with a benzodiazepine agent may help if anxiety is present.

B. Anticoagulation, Antiplatelet, and Thrombolytic Therapy
Coronary thrombosis plays a prominent role in the pathophysiology of unstable angina and its progression to myocardial infarction, and antithrombotic therapy plays an important role in treatment. Patients should receive a combination of antiplatelet and anticoagulant agents. Aspirin, 81-325 mg daily, and heparin (low molecular weight or unfractionated) should be commenced on presentation. Several trials have shown that low-molecular-weight heparin (and specifically enoxaparin 1 mg/kg subcutaneously every 12 hours) is somewhat more effective than unfractionated heparin in preventing recurrent ischemic events in the setting of acute coronary syndromes. However, the recent SYNERGY trial showed that unfractionated heparin and enoxaparin had similar rates of death or (re)infarction in the setting of frequent early coronary intervention. The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial demonstrated a 20% reduction in the composite end point of cardiovascular death, myocardial infarction, and stroke with the addition of clopidogrel (300 mg loading dose, 75 mg/d for 12 months) in patients with non-ST segment elevation acute coronary syndromes. When treated with clopidogrel, the optimal aspirin dose appears to be 81 mg/d (versus 160 mg/d or 325 mg/d) based on similar thrombotic event rates and lower rates of bleeding.

Small molecule inhibitors of the platelet glycoprotein IIb/IIIa receptor are useful adjuncts in high-risk patients (usually defined by fluctuating ST segment depression or positive biomarkers) with acute coronary syndromes, particularly when they are undergoing PTCA or stenting. Tirofiban, 0.4 ug/kg/min for 30 minutes, followed by 0.1 ug/kg/min, and eptifibatide, 180 ug/kg bolus followed by a continuous infusion of 0.1 ug/kg/min, have both have been shown to be effective when added to heparin. Downward dose adjustments are required in patients with reduced renal function.

Fibrinolytic therapy should be avoided in patients without ST segment elevation since they generally have a patent culprit artery, and since the risk of such therapy appears to outweigh the benefit.

C. Nitroglycerin
The nitrates are first-line anti-ischemic therapy for acute coronary syndromes. Nonparenteral therapy with sublingual or oral agents or nitroglycerin ointment is usually sufficient. If pain persists or recurs, intravenous nitroglycerin should be started. The usual initial dosage is 10 ug/min. The dosage should be titrated upward by 10-20 ug/min (to a maximum of 200 ug/min) until angina disappears or mean arterial pressure drops by 10%. Careful - usually continuous - blood pressure monitoring is required when intravenous nitroglycerin is used. Avoid hypotension (systolic BP

< 100 mm Hg). Tolerance to continuous nitrate infusion is common.

D.ß-Blockers
These agents are also a part of the initial treatment of unstable angina unless otherwise contraindicated. If the patient has no physical findings of heart failure, these agents can usually be started without measurements of left ventricular function. Patients with evidence of large or multiple old infarctions are an exception. Use of agents with intrinsic sympathomimetic activity should be avoided in this setting. The goal of acute treatment is to reduce the heart rate below 60-70/min. Oral medication is adequate in most patients, but intravenous treatment with metoprolol, given as three 5 mg doses 5 minutes apart, achieves a more rapid effect. Oral therapy should be aggressively titrated upward as blood pressure permits.

E. Calcium Channel Blockers
Calcium channel blockers have not been shown to favorably affect outcome in unstable angina, and they should be used primarily as third-line therapy in patients with continuing symptoms on nitrates and ß-blockers or those who are not candidates for these drugs. In the presence of nitrates and without accompanying ß-blockers, diltiazem or verapamil is preferred, since nifedipine and the other dihydropyridines are more likely to cause reflex tachycardia or hypotension. The initial dosage should be low, but upward titration should proceed rapidly.

F. Intra-aortic Balloon Counterpulsation (IABC)
IABC can both reduce myocardial energy requirements (systolic unloading) and improve diastolic coronary blood flow. This approach is sometimes employed to stabilize patients prior to angiography or revascularization, but with modern techniques it is rarely necessary.

Prognosis & Indications for Revascularization

The majority of patients can be rendered pain free with these measures. Patients who do not become ischemia free on medical therapy should have early coronary arteriography and revascularization. Controlled trials have reported mixed results as to whether a strategy of routine coronary angiography and revascularization is superior to aggressive medical therapy and selective revascularization in patients with recurrent ischemia or very positive stress tests. Recent trials that have employed both platelet glycoprotein IIb/IIIa antagonists and stents in the majority of patients have favored an early but not necessarily immediate invasive strategy (eg, within several days and prior to discharge). Depending on the stringency of the definition of unstable angina, 10-30% of patients will have an early infarction, and the 1-year mortality rate is 10-20%. Elevated troponin I or T concentrations and “silent” ST segment shifts have both identified patients at higher risk for subsequent myocardial infarction or recurrence of severe ischemia. These markers identify a subset of patients who benefit from the early use of glycoprotein IIb/IIIa receptor antagonists and, most likely, early revascularization.

Because recurrent episodes, infarction, and sudden death may occur following relief of unstable angina, additional evaluations should be performed in patients who have been stabilized, consisting of either (1) early exercise or pharmacologic stress testing to identify high-risk subsets for further invasive evaluation or (2) coronary arteriography. The choice of approach should be individualized based on the patient’s age and general health as well as the severity of symptoms and signs of ischemia (Table 10-5). The artery responsible for the ischemia can usually be determined from electrocardiographic or scintigraphic changes during pain, and the lesion is often amenable to PTCA. If revascularization is not performed, long-term management is the same as that outlined for stable angina pectoris.

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