The American College of Cardiology (ACC) and the American Heart Association (AHA) have updated the ACC/AHA guidelines for the management of myocardial infarction. Developed by the ACC/AHA Task Force on Practice Guidelines, the guidelines cover a wide scope, from management in the field, emergency department and hospital to predischarge evaluation, cardiac rehabilitation and long-term management. A section on pharmacotherapy discusses the use of nitroglycerin, platelet-active agents, thrombolytic therapy, antithrombotic or anticoagulant agents, beta-adrenergic blockers, angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers, antiarrhythmic agents, magnesium and inotropic agents. The guidelines provide new information on the use of glycoprotein IIb/IIIa inhibitors, the role of serum cardiac markers such as troponin, the place for coronary angioplasty and the use of heparin after fibrinolytic agents have been administered.

The complete text of the guidelines can be accessed online at the ACC Web site (http://www.acc.org click on the section called “Clinical Information”) and the AHA Web site (http://www.americanheart.org click on the heading “Publications,” under the section called “Science and Professionals”). At both Web sites, all of the changes that were made in the guidelines are shown on the online document. The executive summary of the guidelines is published in the August 31, 1999 issue of Circulation and the complete text is published in the September 1999 issue of the Journal of the American College of Cardiology.

As is the custom of ACC/AHA guidelines, the recommendations are classified according to the level of evidence for the recommendations, as follows:

• Class I—Conditions for which there is evidence and/or general agreement that this procedure is useful and effective.

• Class II—Conditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the procedure.

• Class IIa—The weight of evidence/opinion is in favor of usefulness/efficacy.

• Class IIb—Usefulness/efficacy is less well established by evidence/opinion.

• Class III—Conditions for which there is evidence and/or general agreement that the procedure is not useful/effective and in some cases may be harmful.

Most of the ACC/AHA recommendations for the management of myocardial infarction remain the same as or constitute only minor changes from those in the 1996 guidelines. For the recommendations that have changed, the modifications reflect the emergence of new data and the advances that have occurred in the management of myocardial infarction. The discussion sections of the guidelines synthesize the findings from clinical studies and provide a rationale for the changes in the recommendations.

The following highlights some of the changes in the revised ACC/AHA guidelines for the management of myocardial infarction.

Serum Cardiac Markers

The section on initial recognition and management in the emergency department includes an update on the use of serum cardiac markers such as creatine kinase (CK) and its MB isoenzyme (CK-MB), troponin I, troponin T, myoglobin and CK-MB isoforms. No specific recommendations for the use of serum cardiac markers were developed in the revised guidelines.

The discussion of serum cardiac markers states that the “ideal serum cardiac marker … should be present early and in high concentration in the myocardium…” Data from clinical trials suggest that troponin I and troponin T provide more prognostic information than the patient's demographic characteristics or the electrocardiographic findings at presentation. Myoglobin is described as a “particularly attractive marker” for the early diagnosis of reperfusion. Troponin I and troponin T have been found to be highly cardiac specific and particularly efficient for the late diagnosis of myocardial infarction. On the other hand, CK-MB subforms may be most efficient for early diagnosis (within six hours) of myocardial infarction.

Primary Coronary Angioplasty

Significant changes have occurred in the recommendations for coronary angioplasty. Compared with the 1996 recommendations for primary percutaneous transluminal coronary angioplasty (PTCA) as an alternative to thrombolytic therapy, the 1999 guidelines specifically describe the settings in which PTCA is recommended in the category of Class I. The revised recommendations specify that PTCA can be considered an alternative to thrombolytic therapy in patients with ST-segment elevation or new (or presumed new) left bundle branch block, provided angioplasty of the infarct-related artery can be performed within 12 hours of the onset of symptoms or beyond 12 hours if ischemic symptoms persist. A Class I recommendation for PTCA also pertains to its use in patients who develop cardiogenic shock. The recommendation states that PTCA can be an alternative “in patients who are within 36 hours of an acute ST-elevation/Q-wave or new left bundle branch block infarction who develop cardiogenic shock, are less than 75 years of age and in whom revascularization can be performed within 18 hours of shock.”

The revised guidelines contain a Class IIb recommendation for PTCA in patients who do not present with ST elevation but who have reduced (less than TIMI grade 2) flow of the infarct-related artery, provided it can be performed within 12 hours of the onset of symptoms.

The recommendations for PTCA also include a Class III recommendation (i.e., evidence indicates “the procedure is not effective/useful …”). The Class III recommendation applies to patients who (1) undergo elective angioplasty of a noninfarct-related artery at the time of acute myocardial infarction; (2) are beyond 12 hours after the onset of symptoms and have no evidence of myocardial ischemia; (3) have received fibrinolytic therapy and have no symptoms of myocardial ischemia and; (4) are eligible for thrombolysis and are undergoing primary angioplasty performed by a low-volume operator in a laboratory without surgical capability.

The discussion section for the PTCA recommendations cites data from the Global Utilization of Streptokinase and TPA for Occluded Arteries (GUSTO) IIb trial, which showed that the incidence of adverse outcomes after six months of follow-up was similar in patients who received thrombolytic therapy (15.7 percent) and in patients who underwent PTCA (13.3 percent). The GUSTO study included 1,138 patients with evolving ST-segment elevation who were seen within 12 hours of the onset of chest pain. After 30 days of follow-up, the incidence of death, recurrent infarction or disabling stroke was 9.6 percent in patients who underwent PTCA compared with 13.6 percent in patients who received thrombolytic therapy.

Also noted in the discussion are the findings from the Second National Registry of Myocardial Infarction (NRMI-2), which suggest that primary PTCA and thrombolytic therapy offer similar efficacy. Data from the preliminary report of the Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock? (SHOCK) trial are described as “the most important contributions” to the revised guidelines. This study revealed that the mortality rate was significantly lower (50.3 versus 63.1 percent) in the 152 patients who underwent emergency revascularization, compared with the mortality rate in the 150 patients who received medical management.

The discussion section for PTCA also cites a recent meta-analysis of 10 randomized trials that included 2,606 patients. The investigators who performed the meta-analysis concluded that on the basis of outcomes at hospital discharge or 30 days, “primary PTCA appears to be superior to thrombolytic therapy… [provided] the success rates for PTCA are as good as those achieved in these trials. Data evaluating longer-term outcome, operator expertise and time delays before treatment are needed before primary PTCA can be recommended universally as the preferred treatment.” Similarly, the ACC/AHA guidelines state that “until more data have more reliably quantified a benefit of primary PTCA over thrombolytic therapy in the community setting, it seems prudent to suggest that institutions that do not have the capability of offering primary PTCA should not feel compelled to develop such services at this time.”

Antithrombotic Therapy

The section on antithrombotic therapy includes the addition of Class IIa recommendations for the use of glycoprotein IIb/IIIa inhibitors. The Class IIa recommendation states that glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide and tirofiban) are “for use in patients having a myocardial infarction without ST-segment elevation who have some high-risk features and/or refractory ischemia, provided they do not have a major contraindication due to a bleeding risk.”

The discussion of glycoprotein IIb/IIIa agents points out that direct comparisons of the different agents are not available. Thus, a specific choice of agent is not recommended.

The Class IIa recommendations for the use of unfractionated heparin have been modified in the updated guidelines. Namely, the recommended regimen has been changed from 70 U per kg to 60 U per kg as a bolus at the initiation of alteplase infusion, followed by an initial maintenance dose of about 12 U per kg per hour (the 1996 guideline cited a maintenance dose of 15 μg per kg per hour). Also in this Class IIa category is the addition of the use of intravenous unfractionated heparin or low-molecular weight heparin subcutaneously in patients with non–ST-segment elevation and in patients not treated with thrombolytic therapy who do not have a contraindication to heparin.

Data from numerous recent trials of thrombolytic therapy are summarized in the guidelines, as are comparative features of the streptokinase, alteplase and reteplase. Use of low-molecular-weight heparin as an adjunct to thrombolysis is discussed.

Cardiovascular Drugs

Recommendations for the use of beta-adrenergic blockers in the setting of acute myocardial infarction include the addition of a Class I recommendation for use of these agents in patients with non–ST-segment elevation infarctions. Other Class I recommendations for beta blockers, which were also in the 1996 guidelines, include use in patients without contraindications to beta-blocker therapy who can be treated within 12 hours of the onset of infarction, in patients with continuing or recurrent ischemic pain and in patients with tachyarrhythmias such as atrial fibrillation with a rapid ventricular response.

A Class IIb recommendation for beta-blocker therapy was formulated for patients with moderate left ventricular failure (the presence of bibasilar rales without evidence of low cardiac output) or other relative contraindications to beta-blocker therapy, provided close monitoring is possible.

A Class III recommendation is given for patients with severe left ventricular failure.

The recommendations for ACE inhibitors and calcium channel blockers remain unchanged in the revised guidelines. The section on pharmacotherapy also includes brief discussions on antiarrhythmic agents such as lidocaine, bretylium, procainamide and amiodarone. With respect to antiarrhythmic agents, no specific recommendations in Class I, IIa, IIb and III categories are in the guidelines.

Preparation for Hospital Discharge

• Predischarge Evaluation. The section on preparation for hospital discharge includes recommendations for the noninvasive evaluation (e.g., stress electrocardiography, scintigraphy, echocardiography) of low-risk patients, assessment of ventricular arrhythmia and coronary angiography. No changes were made in any of the recommendations for predischarge evaluation.

• Lipid Levels. The only change made in the recommendations for the management of lipid levels is the Class IIb recommendation that drug therapy with niacin or gemfibrozil may be added to diet regardless of the low-density and high-density lipoprotein levels when the triglyceride level is more than 200 mg per dL (2.26 mmol per L). The 1996 guideline cited a triglyceride level of more than 400 mg per dL (4.52 mmol per L).

• Long-term Beta-blocker Therapy. Changes in the recommendations for the use of long-term beta-blocker therapy include the addition of a Class IIa recommendation for use in survivors of non–ST-segment elevation infarction. A Class IIb recommendation was added for use in patients with moderate or severe left ventricular failure or other relative contraindications to beta-blocker therapy, provided close monitoring is possible. No changes were made in the Class I recommendation for beta-blocker therapy, which recommends therapy in “all but low-risk patients without a clear contraindication” to therapy.

• Estrogen Replacement Therapy. The Class IIa recommendation for estrogen replacement therapy following myocardial infarction was modified in the revised recommendations. In the 1996 recommendations, the Class IIa recommendation for estrogen replacement therapy states that “all postmenopausal patients… should be carefully counseled about the potential beneficial effects of estrogen replacement therapy” and offered the option. The 1999 Class IIa recommendation, however, states that hormone replacement therapy with estrogen plus progestin should not be given to postmenopausal women who were not receiving such therapy before the infarction. The recommendations also state that hormone replacement therapy can be continued in postmenopausal women who were receiving this therapy before the myocardial infarction.