DALLAS--Significant improvement has occurred in the management of unstable angina in recent years, and the new American College of Cardiology/American Heart Association (ACC/AHA) guidelines for the condition reflect this change.[1] The new guidelines also cover non-ST-segment myocardial infarction, because this acute coronary syndrome, although more severe, is closely related to unstable angina in both pathogenesis and presentation.

Melvin D. Cheitlin, MD, a member of the ACC/AHA committee that created the new guidelines, discussed them in an interview with PULMONARY REVIEWS. Dr. Cheitlin, the former Chief of Cardiology at San Francisco General Hospital, highlighted key changes that were made to the guidelines since the previous version was published in 1994, including the use of cardiac-specific troponin markers to stratify patient risk and indications for the recently introduced platelet glycoprotein IIb/IIIa receptor antagonists.

STRATIFYING RISK

The first recommendation in the 2000 guidelines concerns patient evaluation. Telephone evaluation alone is inappropriate for patients with chest discomfort or other symptoms consistent with an acute coronary syndrome. Such patients should be referred to an appropriate facility for physician assessment and a 12-lead electrocardiogram (ECG), Dr. Cheitlin stressed.

A critical early step in managing these patients is to determine their risk for death and nonfatal cardiac ischemic events, since this will influence therapy. Risk stratification usually incorporates multiple factors, including symptoms, physical and ECG findings, and biomarkers of cardiac injury.

The new guidelines use the previous definitions of low, intermediate, and high risk. However, the guidelines authors acknowledged that risk stratification is a complex, multivariable problem that cannot be easily summarized. Thus, they recommended that a careful individualized assessment be performed for every patient. Among the findings that strongly predict an adverse outcome are an accelerating tempo of ischemic symptoms, the presence of left ventricular failure or pulmonary edema, and markedly elevated cardiac-specific troponin levels.

Until recently, creatine kinase-MB was the primary biomarker of cardiac injury because the test for it is rapid, cost-efficient, and accurate. Now, however, one of the cardiac-specific troponins is preferred because the new monoclonal antibody-based immunoassays for them provide greater sensitivity and specificity, among other advantages. However, measurement of creatine kinase-MB is still acceptable as a marker of myocardial necrosis.

"The higher the troponin level, the higher the patient's risk," pointed out Dr. Cheitlin, who is also an Emeritus Professor of Medicine at the University of California, San Francisco. "Mortality risk, for example, can be up to 7.5 times greater when the troponin result is positive than when it is negative."

An unstable angina diagnosis is appropriate when biomarkers of cardiac injury are absent, the guidelines note. When such a biomarker is present, the patient has had a non-ST-segment myocardial infarction resulting in myocardial necrosis.

HOSPITALIZATION REQUIREMENTS

Patients with unstable angina or non-ST-segment myocardial infarction should be hospitalized if their symptoms are recurrent, they have angina at rest, and/or they have ECG evidence of ST-segment deviations or positive biomarkers for cardiac injury. If such patients are hemodynamically stable, they can be admitted to a step-down unit; those with continuing discomfort and/or hemodynamic instability should be placed in a cardiac care or similar intensive care unit.

All hospitalized patients should be treated early with aspirin, a ß-blocker, and an anticoagulant unless a contraindication to one of these agents is present. Many patients, especially those with risk factors, will also benefit from a glycoprotein IIb/IIIa inhibitor. The need for other immediate treatments is dictated by each patient's condition; for example, many will require a nitrate for pain relief. Once the immediate treatments have been administered, a decision can then be made about whether to use an early invasive or early conservative strategy.

OLD AND NEW TREATMENTS

Like the previous guidelines, the new ones urge immediate anti-ischemic and antithrombotic therapy for patients with acute coronary syndromes, to reduce the risk of death. Intravenous ß-blockers are the anti-ischemic drugs of first choice. This recommendation is based on their demonstrated benefit in patients with acute myocardial infarction, as well as their ability to reduce cardiac work and myocardial oxygen demand.

Aspirin is still an excellent choice as an antiplatelet agent. Patients should be given aspirin as soon as possible; the usual starting dose is 160 to 325 mg. "Have them chew the first dose so that it is absorbed more rapidly," advised Dr. Cheitlin. Patients should continue to take 81 to 325 mg/d of aspirin indefinitely, although they no longer have to chew it. Those who cannot tolerate aspirin should receive a thienopyridine, such as clopidogrel or ticlopidine.

Heparin is also a key part of antithrombotic therapy for acute coronary syndromes. Studies have shown that combining unfractionated or low-molecular-weight heparin with aspirin reduces the risk of death or myocardial infarction by about 50% to 60% during the first week of therapy.

However, unfractionated heparin has important disadvantages, such as poor bioavailability, marked variation in effectiveness between patients, and the need for intravenous administration. Thus, it requires constant monitoring and titration based on the activated partial thromboplastin time. "It is intensive and expensive," noted Dr. Cheitlin.

The newer low-molecular-weight heparins, on the other hand, are administered subcutaneously every 12 hours and do not require monitoring. Furthermore, they are less likely than unfractionated heparin to induce thrombocytopenia. However, they do seem more likely to cause minor bleeding.

The platelet glycoprotein IIb/IIIa receptor antagonists eptifibatide, tirofiban, and abciximab are indicated in patients with acute coronary syndrome who are at high risk or will be having a percutaneous coronary intervention. "These drugs are intravenous, very expensive, and can cause bleeding, so we do not like to give them to everybody, especially if the patient is low risk and has responded to aspirin," Dr. Cheitlin said.

These agents stop platelet aggregation by preventing binding of fibrinogen to platelet receptors. They can be given with aspirin and unfractionated heparin. The safety and efficacy of these drugs in combination with low-molecular-weight heparin are currently under investigation.

CONSERVATIVE VS INVASIVE

Two treatment strategies have evolved for unstable angina and non-ST-segment myocardial infarction--early conservative and early invasive. Because a strong argument can be made for each of these approaches, the authors of the new guidelines reviewed the relevant studies especially carefully.

In early conservative treatment, coronary angiography is reserved for patients who, despite vigorous medical intervention, have evidence of recurrent ischemia (angina at rest or with minimal activity or with dynamic ST-segment changes) or a strongly positive stress test result. In early invasive treatment, angiography and a revascularization procedure are routinely recommended for patients without obvious contraindications.

The early conservative strategy has two theoretical advantages: It is probably less expensive than the early invasive strategy, and it avoids the risks associated with early revascularization. Theoretical advantages of the early invasive strategy are that it provides information for risk stratification, reduces the risk of subsequent hospitalization, and may improve survival.

The guidelines suggest that the invasive approach be used for patients with a high-risk condition, such as recurrent angina/ischemia, congestive heart failure, depressed left ventricular systolic function, hemodynamic instability, previous bypass procedure, or nonsustained or sustained left ventricular tachycardia. In the absence of a high-risk condition, either an early conservative or an early invasive strategy is appropriate.

--Timothy Begany

Reference
1. Braunwald E, Antman EM, Beasley JW, et al. ACC/AHA guidelines for the management of patients with unstable angina and non--ST-segment elevation myocardial infarction. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina). J Am Coll Cardiol. 2000;36:970-1062.

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