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Acute Coronary Syndromes

The term "acute coronary syndromes" refers to a spectrum of disorders characterized by ischemic discomfort at rest. Specifically excluded from these disorders would be non-coronary chest pain which may prompt admission to the hospital but is due to non-cardiac causes. Patients with ST segment elevation on the electrocardiogram frequently evolve into Q-wave or non-Q-wave myocardial infarction. Patients without ST segment elevation are classified as unstable angina if there are no biochemical markers of necrosis, or as non-Q-wave MI if there is evidence of myocardial necrosis. With sensitive new troponin assays, it is clear that these distinctions may be somewhat artificial. Furthermore, some patients without initial ST segment elevation may progress to Q-wave myocardial infarction.

Unstable angina can be considered as a clinical syndrome falling between stable angina and myocardial infarction and generally requires the presence of rest pain. One clinical practice guideline notes (1) the various presentations of unstable angina in table 1. A classification of patients with symptoms suggesting unstable angina is listed in table 2 which relates the likelihood of significant coronary artery disease.

Initial drugs to consider in the management of unstable angina include aspirin, heparin, nitrates, beta blockers, and glycoprotein IIb-IIIa inhibitors. Pharmacologic therapy should be initiated in the Emergency Room. Supplemental oxygen may be considered with cyanosis, respiratory distress, or high risk features. One should monitor for adequate arterial oxygenation , heart attack, myocardial infarction, infraction, miocardial, angina, angena with finger pulse oximetry or blood gas determinations. Patients should be placed on continuous ECG monitoring for ischemia and arrhythmia detection. Intravenous thrombolytic therapy is not indicated in patients who do not have ST segment elevation or left bundle branch block on their 12-lead electrocardiogram.

Table 3 lists the short-term risk of death or non-fatal myocardial infarction in patients with symptoms suggesting unstable angina, based on clinical factors (1). Patients who are judged to be at low risk for such events, may be safely evaluated further as outpatients providing that they respond immediately and continuously to medical treatment. Intensive medical management of such patients includes establishing intravenous access.

nitrates, and beta blockers (1,2). Glycoprotein IIbKIIa inhibitors are emerging as standard therapy for acute coronary syndromes. Calcium channel blockers can be considered in patients who have significant hypertension, in patients with refractory ischemia on beta blockers and in those variant angina. In general, it is prudent to use maximal medical therapy for 24 hours before declaring any patient a failure of medical therapy. However, patients who have one or more recurrences of severe prolonged (>20 minutes) ischemic episodes especially if accompanied by pulmonary edema, new or worsened mitral regurgitation, hypotension, or new ST-T changes should be triaged early.

Heparin should be administered so that an aPTI' is 1.5-2.5 times control. When aPTT is stable with every 6-hour monitoring, then it can be monitored every 24 hours. Low molecular weight heparin is a good substitute for heparin (3). In patients at lower risk, heparin may be discontinued after 3-5 days. The target rate for administration of beta blockers (such as intravenous metoprolol) is a target heart rate of 50-60 beats per minute. Patients can then be converted to an oral regimen of beta blockers after the intravenous load. Intravenous nitroglycerin is very helpful and can be switched to oral or topical nitrates.

Patients with continuing pain after the above medical regimen can be given morphine to relieve pain.

One of the major management questions about unstable angina/non-Q-wave myocardial infarction is if and when should patients be considered for cardiac catheterization and potential coronary intervention. The TIMI III-B trial (4) randomized 1,473 patients with this syndrome into an earlier invasive strategy and an early conservative strategy with catheterization if ischemia continued. Patients were initially all treated with standard medical therapy. The primary composite endpoint of death, myocardial infarction, and a positive exercise tolerance test at 6 weeks was not different between the two groups of patients.

The recently published VANQWISH trial (5) had 920 patients with non-Q-wave myocardial infarction who were randomized to an invasive strategy of pre-discharge angiography and revascularization compared with a conservative strategy of medical management with intervention reserved only for recurrent ischemia. Preliminary results showed a higher rate.

The Rita 11 trial (7) studied 1,018 patients with coronary artery disease about half of whom presented with unstable angina. All patients had angiography and were deemed eligible for either medical therapy or angioplasty.

Thus, controversy remains over the optimal management strategy of patients with unstable angina and non-Q-wave MI. Since studies do not strongly support one strategy over the other.

The management of unstable angina/non-Q-wave MI has changed considerably since the introduction of the glycoprotein IIb/IIIa receptor blockers. This class of drugs is emerging as standard therapy in acute coronary syndromes and coronary interventions. The principal studies with tirofiban have been the PRISM and PRISM Plus studies. Tirofiban is a reversible non-pepfide glycoprotein IIb/IIIa platelet receptor blocker indicated in combination with heparin for the management of acute coronary syndrome patients. The PRISM study (8) evaluated the effect of tirofiban versus heparin in medically stable patients with acute coronary syndromes. All patients received aspirin before randomization. Relative to the composite endpoint of refractory ischemia, MI or death at 48 hours, the composite endpoint was 3.8% in the tirofiban group and 5.6% in the heparin group. The PRISM Plus study (9) allowed patients to have medical stabilization, and then investigators were encouraged to perform coronary angiography and angioplasty, if appropriate, between 48 and 96 hours after randomization while continuing study drugs which included randomization to tirofiban without heparin and tirofiban with heparin. The study was stopped prematurely because of an excess mortality, 4.6% in the tirofiban group compared to 1.1% in the heparin group, and 1.5% in the combination group. The mortality excess was not significant at 30 days or 6 months follow-up.

Abciximab is the FAB fragment of the chimeric human-murine monoclonal antibody 7E3. It binds to the glycoprotein llb/IIIa receptor of human platelets and inhibits platelet aggregation. It is indicated as an adjunct to PTCA for the prevention of acute cardiac ischemic complications at high risk of acute closure of the treated coronary vessel. This would include PTCA in patients who have unstable angina or a non-Q-wave myocardial infarction. The EPIC trial (11) was a multicenter, double-blind, placebo-controlled trial in patients undergoing PTCA or atherectomy. Aspirin was administered orally 2 hours prior to the planned procedure and then once a day. The primary endpoint was the occurrence of any of the following events within 30 days of PTCA: death, myocardial infarction with a need for urgent intervention or recurrent ischemia, urgent coronary artery bypass graft surgery, and coronary stent or an intra-aortic balloon pump. In the first 30 days, the primary endpoint was reached in 12.8% of the placebo patients, 11.5% of those who received a bolus only of absiximab, and 8.3% of those who received a bolus plus infusion of Abciximab. The most common complication encountered during this trial was bleeding.

Eptifibatide is a GP IIb/IIa inhibitor which is approved for the treatment of patients with acute coronary syndrome, including those who are to be managed both medically and with PTCA. A total of 14,718 patients were treated in the two phase, 3 clinical trials (PURSUIT and IMPACT 2). Treatment was given on top of aspirin and heparin with an intravenous bolus

Aspirin may be replaced in certain circumstances by ticlopidine, or a newer ticlopidine analog, clopidogrel. Clopidogrel is a new anti-platelet agent belonging to the thenopyridine class. It irreversibly binds to adenosine diphosphate (ADP) receptors.