The purpose of this guideline is to define diagnostic and management strategies likely to maximize therapeutic benefit for patients with unstable angina. Recommendations are expected to be flexibly applied to individual patients by informed practitioners using reasonable clinical judgment.
The purpose of this executive summary is to describe the process of guideline development and provide an overview of its scope and content. Clinicians desiring a summary of this guideline, designed to guide actions during actual patient management, may wish to obtain the companion document designed for this purpose, Quick Reference Guide for Clinicians, Number 10, Diagnosing and Managing Unstable Angina, which is available upon request from the Agency for Health Care Policy and Research (AHCPR).
This clinical practice guideline on the diagnosis and management of unstable angina was developed by a private-sector panel of emergency, family and internal medicine specialists; cardiologists; cardiac surgeons; nurses; and consumer and public health representatives. The panel was convened and supported by AHCPR and the National Heart, Lung, and Blood Institute (NHLBI). The panel was assisted in all aspects of its work by a professional staff from Duke University.
Using the National Library of Medicine's medical subject headings, staff conducted a search of available data bases which yielded over 5,000 abstracts relating to unstable angina. Nearly 2,500 relevant articles were organized by an outline of topics related to the usual management steps in patients with unstable angina. Review of topically ordered abstracts identified 130 randomized clinical trials, 319 clinical studies of excellent quality, and 1,351 clinical studies of good quality which were analyzed for appropriateness of methodology and summarized for panel review. Only results of published studies and studies known to be accepted for publication were considered in reaching panel recommendations. However, the text of the guideline refers in general terms to findings of a small number of major randomized trials which have recently been presented at national meetings. These trials are mentioned because information available at the time of their publication will likely influence management decisions in patients with unstable angina.
Studies on topics corresponding to individual guideline recommendations were reviewed together, and the overall quality of scientific evidence available was graded A, B, or C. A strength of evidence = A grade required at least one randomized controlled trial as part of the body of literature of overall good quality and consistency addressing the specific recommendation. A strength of evidence = B grade required availability of well-conducted clinical studies but no randomized clinical trials on the topic of the recommendation. A strength of evidence = C grade indicated absence of directly applicable clinical studies of good quality. These recommendations were made by panel consensus using related information, general principles of medical care, and clinical experience. An informal process of group discussion was used to achieve panel consensus on the language and strength of evidence of each recommendation.
Evidence was poor or lacking to assist panel deliberation on many aspects of diagnosing and managing unstable angina, and the quality of available scientific evidence did not always relate to the clinical importance of the topic. Therefore, the language used in each recommendation reflects the perceived importance of the statement in patient care, and the strength of evidence grade reflects the body of scientific literature available to support the recommendation. The guideline was revised to reflect the thoughtful comments of 75 individuals representing 24 professional peer organizations with interest and expertise in unstable angina. The guideline was reviewed and tested by 44 practitioners for practicality and reasonableness in clinical practice.
Throughout this guideline, unstable angina is defined as having three possible presentations: symptoms of angina at rest (usually prolonged >20 minutes), new onset (<2 months) exertional angina of at least Canadian Cardiovascular Society Classification (CCSC) class III in severity, or recent (<2 months) acceleration of angina as reflected by an increase in severity of at least one CCSC class to at least CCSC class III. In most, but not all, of these patients, symptoms will be caused by significant coronary artery disease (CAD). Variant angina, non-Q-wave myocardial infarction (MI), and post-MI (>24 hours) angina are part of the spectrum of unstable angina.
A diagnosis of unstable angina requires determination of the likelihood of CAD and assessment of the severity of presentation. The likelihood of significant CAD in patients presenting with acute chest pain syndrome is related to the physician's assessment of the patients' symptoms as angina, categorized as definite, probable, probably not, or definitely not angina; evidence of prior MI or other indicators of CAD; and the sex, age, and number of major risk factors for atherosclerosis. Other factors important in diagnosis of unstable angina include a known history of variant angina or cocaine use and details of prior treatment for known or suspected CAD. Physical findings of value include a transient S3or S4mitral regurgitation (MR) murmur or precordial lift during an episode of discomfort. The presence of bruits or pulse deficits suggesting extracardiac vascular disease increases the likelihood of CAD.
The standard 12-lead electrocardiogram (ECG) provides crucial information in the diagnosis of unstable angina, and recordings during periods of both pain and absence of pain are useful. Markers of high likelihood of CAD on ECG include ST-segment elevation or depression >e;1 mm, deep symmetrical T-wave inversion in multiple precordial leads, or any transient ECG change occurring during pain. ST-segment depression >e;0.5 mm but <1 mm, T-wave inversion >e;1 mm in leads with dominant R waves, and nonspecific ST- and T-wave changes are features of patients with an intermediate likelihood of CAD. These clinical features on initial evaluation can be used to stratify patients into high, intermediate, and low likelihood of CAD.
Risk of death or ischemic complications in patients with unstable angina is lower than with MI but higher than with stable angina. This risk is greater when symptoms first occur and declines rapidly to baseline levels, defined by characteristics of patients with stable angina, within about 2 months of initial presentation. The prognosis of patients presenting with symptoms suggestive of unstable angina is determined by the likelihood of CAD, the tempo of the recent clinical course, and by factors that affect the likelihood that a patient will survive should an acute ischemic event occur. Important historic elements to define the tempo of presentation of symptoms include the current frequency and change in frequency and severity of angina over the recent time prior to presentation. Prolonged episodes of severe chest pain are important markers of high-risk unstable angina. The important prognostic elements on physical examination include any evidence of acute congestive heart failure (CHF), a new or worsening MR murmur, or systemic hypotension, particularly during an episode of severe pain. ECG findings suggesting increased risk are dynamic shifts in ST-segment change with >e;1 mm of ST-segment depression or elevation or T-wave inversions that resolve when symptoms are relieved. Through the use of these characteristics, patients with the diagnosis of unstable angina can be stratified into three groups characterized as having a low, intermediate, or high risk of death or nonfatal MI. As patients progress through the clinical course of their disease, additional events (such as recurrent ischemic episodes) may occur, and additional data (such as an assessment of left ventricular [LV] ejection fraction [EF]) may be obtained that permit the assessment of prognosis to be updated or refined.
The panel recommends informing and involving the patient and his or her family or advocate in all important care decisions. Sufficient information describing diagnosis, prognosis, and treatment options should be given to patients to permit them to choose care alternatives they prefer.
Because the diagnosis of unstable angina can be quite difficult, initial evaluation of patients with symptoms consistent with ischemic pain should usually take place in a medical facility with the capability of performing an ECG and not over the telephone. In general, patients with ongoing pain should be evaluated initially in an emergency department (ED) with the capability of providing ECG monitoring, advanced cardiac life support (ACLS), intravenous (IV) pharmacologic therapy, and radiographic examinations. Patients without ongoing pain may be evaluated initially in outpatient facilities with diagnostic capabilities but without support necessary to treat the acutely unstable patient. The objective of the initial evaluation is to assess diagnostic probabilities and evaluate the short-term risk of death and other major complications. The results of this evaluation will set the pace of further care and form the basis of the working diagnosis. The two goals of initial management of patients with unstable angina are to institute immediate therapy and move the patient to a proper environment for the monitoring of complications. In many cases, stabilization progresses concurrently with patient evaluation.
Initial evaluation should be complete and treatment begun within an hour of presentation to the ED. All patients with unstable angina should receive aspirin (ASA) unless they have documented hypersensitivity or active bleeding. Those with persistent symptoms or ECG changes suggesting ongoing ischemia should also receive nitroglycerin (NTG). Beta blockers and IV heparin are indicated for patients with intermediate- and high-risk unstable angina who do not have contraindications to these drugs. Unless patients have a compelling history for acute MI accompanied by ST-segment elevation or left bundle branch block (LBBB) on the 12-lead ECG, IV thrombolytic therapy is not indicated.
Patients with unstable angina and high-risk features with persistent ischemia or hemodynamic instability should be admitted to an intensive care unit (ICU). Patients at intermediate risk may be admitted to an ICU, intermediate care unit, or other cardiac care environment. All high-risk patients and many intermediate-risk patients should have serial cardiac enzymes and ECGs to exclude the possibility of acute MI. Low-risk patients can be further evaluated and managed as outpatients. Patients with acute MI with indications for thrombolytic or other reperfusion therapy, patients with stable angina, and patients considered not to have CAD are excluded from this guideline at the conclusion of initial evaluation.
Patients judged to be at low risk when initially seen who, therefore, are not admitted to a medical facility, should have a thorough evaluation scheduled within 72 hours if a definitive evaluation cannot be completed at the time of initial presentation. At the time of subsequent evaluation, attention is directed toward further assessing the cause of the patient's symptoms, evaluating the risk of future adverse cardiac events, and providing adequate symptom relief.
Patients considered not to have CAD after this evaluation should be reassured that their symptoms are very unlikely to be due to CAD and should be evaluated appropriately to determine the cause of the symptoms. The care of patients thought to have CAD should match the severity of the process. Most patients will require some pharmacologic therapy to relieve symptoms. In addition, exercise or pharmacologic stress testing will usually be a part of this detailed workup. All patients should receive information on the modification of CAD risk factors.
Patients considered to have ongoing manifestations of unstable angina should receive intensive medical management. The goals of this phase of care are to relieve pain and ischemia and to prevent the progression of the underlying disease process to MI or death. ASA, heparin, nitrates, and beta blockers begun at the time of initial evaluation should be titrated to a dosage adequate to relieve ischemia but avoid hemodynamic compromise. Morphine sulfate may be necessary to help relieve severe anginal symptoms that have not resolved with initial therapy. Calcium channel blockers should not be used as initial therapy but can be added to the regimen of patients who are unable to tolerate nitrates or beta blockers or in whom these agents were not effective. Calcium channel blockers should not be given to patients with pulmonary edema or evidence of LV dysfunction. Aggressive medical management can control the presenting symptoms of most patients with unstable angina.
Careful monitoring of patients for recurrent ischemia should continue after the desired level of medical therapy has been reached. The presence of recurrent symptoms may indicate a need for a more intensive medical regimen or triage to early cardiac catheterization and revascularization. Unless complications of ischemia are noted, an optimal medical regimen should be pursued for >e;24 hours before declaring it a failure. However, to use this time as an absolute requirement in the case of every patient would be inappropriate or even dangerous. Generally, if anginal symptoms persist for >1 hour after aggressive medical therapy, which includes ASA, heparin, IV nitrates, and beta blockers, the patient should be reevaluated more comprehensively to be sure there are no unaddressed precipitating factors, reconsider the possibility of noncoronary diseases that may mimic unstable angina, and reaffirm that the most appropriate diagnosis remains unstable angina and not acute MI or other more serious illness.
Patients with high- or intermediate-risk unstable angina whose symptoms have been controlled for 24 hours with intensive medical management will have progressed to a lower risk phase and are appropriate for nonintensive medical management. Patients with intermediate or low risk may be admitted directly into this phase after initial evaluation in the ED. During nonintensive medical management, the emphasis shifts from acute stabilization to the design of a maintenance medical regimen that will suppress reactivation of acute disease activity. Failure of therapy at this phase of care is indicated by recurrent angina refractory to treatment for >20 minutes or recurring more than once on nonparenteral medication. These patients are expected to return to intensive medical management. Other objectives of care often include optimization of the therapeutic regimen and noninvasive testing for risk stratification.
Important management decisions in patients with unstable angina revolve around ongoing risk stratification. In some patients the early clinical course will be characterized by recurrent ECG-documented ischemia. In other patients further evaluation will suggest that the initial diagnosis of unstable angina may have been incorrect. These patients, who are recognized by clinical presentation to have such a high or low probability of high-risk CAD that further risk stratification by noninvasive testing would not alter management, and patients whose other comorbid conditions make stress testing unnecessary or inappropriate have no need to undergo noninvasive testing. Unless cardiac catheterization is indicated, all other patients hospitalized for unstable angina should undergo noninvasive testing after stabilization has been achieved and prior to discharge or as soon as possible thereafter. In this context, noninvasive testing is most useful to assess the adequacy of current therapy, estimate prognosis, and guide decisions on further evaluation and management.
Common indications for cardiac catheterization in patients with unstable angina include: (1) failure to stabilize with adequate medical therapy; (2) recurrent unstable angina; (3) high-risk result of noninvasive test; (4) prior revascularization procedure; and (5) diagnosis or exclusion of significant CAD in patients with multiple clinical episodes of unstable angina without objective documentation of ischemia. Individual patient characteristics and preferences should temper application of these general indications to specific clinical situations.
The goal of cardiac catheterization in patients with unstable angina is to provide detailed structural information necessary to assess prognosis and select an appropriate long-term management strategy. The procedure is usually helpful in choosing between medical therapy, percutaneous transluminal coronary angioplasty (PTCA), or coronary artery bypass graft (CABG) surgery in patients with unstable angina who remain at significant risk for future cardiac events. Patients with extensive comorbidity felt not to be suitable for revascularization and patients who do not wish to consider interventional therapy should not undergo diagnostic catheterization.
Patients found at catheterization to have significant left main disease (>e;50%) or significant (>e;70%) three-vessel disease with depressed LV function (EF <0.50) should undergo CABG to improve survival as well as relieve symptoms. Patients with two- or three-vessel disease with proximal severe subtotal stenosis (>e;95%) of the left anterior descending coronary artery (LAD) may also experience a survival benefit from revascularization. Other patients are appropriately treated for control of anginal symptoms by CABG, PTCA, or medical therapy.
Patients responding to intensive and nonintensive medical therapy and patients undergoing CABG or PTCA during their admission should be instructed on appropriate activities after hospital discharge. Discharge plans should include provisions for clinical followup and risk-factor modification. Continued long-term management of the patient with unstable angina should include ASA therapy indefinitely unless contraindicated. Patients who have stable symptoms at followup may be managed as if they have stable angina.
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