American College of Cardiology

BRAUNWALD ET AL., MANAGEMENT OF PATIENTS WITH UNSTABLE ANGINA AND NON-ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION UPDATE
http://www.acc.org/clinical/guidelines/unstable/incorporated/index.htm

ACC/AHA 2002 Guideline Update 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)

I. Introduction

A. Organization of Committee and Evidence Review

The ACC/AHA Task Force on Practice Guidelines was formed to make recommendations regarding the diagnosis and treatment of patients with known or suspected cardiovascular disease. Coronary artery disease (CAD) is the leading cause of death in the United States. Unstable angina (UA) and the closely related condition non-ST-segment elevation myocardial infarction (NSTEMI) are very common manifestations of this disease. In recognition of the importance of the management of this common entity and of the rapid advances in the management of this condition, the need to revise guidelines published by the Agency for Health Care Policy and Research (AHCPR) and the National Heart, Lung, and Blood Institute (NHLBI) in 1994 ⁽¹⁾ was evident. This Task Force therefore formed the current committee to develop guidelines for the management of UA and NSTEMI, supported by the Agency for Healthcare Research and Quality's UCSF-Stanford Evidence-Based Practice Center. This document should serve as a useful successor to the 1994 AHCPR guideline.

The committee members reviewed and compiled published reports through a series of computerized literature searches of the English-language literature since 1994 and a final manual search of selected articles. Details of the specific searches conducted for particular sections are provided when appropriate. Detailed evidence tables were developed whenever necessary with the specific criteria outlined in the individual sections. The recommendations made were based primarily on these published data. The weight of the evidence was ranked highest (A) if the data were derived from multiple randomized clinical trials that involved large numbers of patients and intermediate (B) if the data were derived from a limited number of randomized trials that involved small numbers of patients or from careful analyses of nonrandomized studies or observational registries. A lower rank (C) was given when expert consensus was the primary basis for the recommendation.

The customary ACC/AHA classifications I, II, and III are used in tables that summarize both the evidence and expert opinion and provide final recommendations for both patient evaluation and therapy:

Class I: Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective

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

Class IIa: 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/treatment is not useful/effective and in some cases may be harmful

A complete list of the thousands of publications on various aspects of this subject is beyond the scope of these guidelines; only selected references are included. The Committee consisted of acknowledged experts in general internal medicine representing the American College of Physicians - American Society of Internal Medicine (ACP-ASIM), family medicine from the American Academy of Family Physicians (AAFP), emergency medicine from the American College of Emergency Physicians (ACEP), thoracic surgery from the Society of Thoracic Surgeons (STS), and general cardiology, as well as individuals with recognized expertise in more specialized areas, including noninvasive testing, preventive cardiology, coronary intervention, and cardiovascular surgery. Both the academic and private practice sectors were represented. The Agency for Healthcare Research and Quality UCSF-Stanford Evidence-Based Practice Center provided support for the guidelines. The original 2000 document was reviewed by 3 outside reviewers nominated by each of the ACC, AHA, and ACEP; 1 outside reviewer nominated by each of the AAFP, ACP-ASIM, European Society of Cardiology, and STS; and 29 outside reviewers nominated by the Committee. The 2002 update was reviewed by 2 outside reviewers nominated by each of the ACC and AHA. This document was approved for publication by the governing bodies of ACC and AHA. These guidelines will be reviewed 1 year after publication and yearly thereafter by the Task Force to determine whether revision is necessary. These guidelines will be considered current unless the Task Force revises them or withdraws them from distribution.

These guidelines overlap several previously published ACC/AHA practice guidelines, including the ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction and the ACC/AHA/ACP-ASIM Guidelines for the Management of Patients With Chronic Stable Angina.

B. Purpose of These Guidelines

These guidelines address the diagnosis and management of patients with UA and the closely related condition NSTEMI. These life-threatening disorders are a major cause of emergency medical care and hospitalization in the United States. In 1996 alone, the National Center for Health Statistics reported 1,433,000 hospitalizations for UA or NSTEMI ⁽²⁾. Nearly 60% of hospital admissions of patients with UA as the primary diagnosis were among persons greater than 65 years old, and 46% of such patients of all ages were women. In 1997, there were 5,315,000 visits to US emergency departments (EDs) for the evaluation of chest pain and related symptoms ⁽³⁾. The prevalence of this presentation of CAD ensures that many healthcare providers who are not cardiovascular specialists will encounter patients with UA/NSTEMI in the course of the treatment of other diseases, especially in outpatient and ED settings. These guidelines are intended to assist both cardiovascular specialists and nonspecialists in the proper evaluation and management of patients with an acute onset of symptoms suggestive of these conditions. These clinical practice guidelines also provide recommendations and supporting evidence for the continued management of patients with these conditions in both inpatient and outpatient settings. The diagnostic and therapeutic strategies that are recommended are supported by the best available evidence and expert opinion. The application of these principles with carefully reasoned clinical judgment reduces, but does not eliminate, the risk of cardiac damage and death in patients who present with symptoms suggestive of UA.

C. Overview of the Acute Coronary Syndrome

1. Definition of terms
UA/NSTEMI constitutes a clinical syndrome that is usually, but not always, caused by atherosclerotic CAD and associated with an increased risk of cardiac death and myocardial infarction (MI). The results of angiographic and angioscopic studies suggest that UA/NSTEMI often results from the disruption of an atherosclerotic plaque and a subsequent cascade of pathological processes that decrease coronary blood flow. Most patients who die during UA/NSTEMI do so because of sudden death or the development (or recurrence) of acute MI (AMI). The efficient diagnosis and optimal management of these patients must derive from information readily available at the time of the initial clinical presentation. The clinical presentation of patients with a life-threatening acute coronary syndrome (ACS) often overlaps that of patients subsequently found not to have CAD. Moreover, some forms of MI cannot always be differentiated from UA at the time of initial presentation.

Acute coronary syndrome has evolved as a useful operational term to refer to any constellation of clinical symptoms that are compatible with acute myocardial ischemia (Figure 1). It encompasses AMI (ST-segment elevation and depression, Q wave and non-Q wave) as well as UA. These guidelines focus on 2 components of this syndrome: UA and NSTEMI. In practice, the term possible ACS is often assigned first by ancillary personnel, such as emergency medical technicians and triage nurses, early in the evaluation process. A guideline of the National Heart Attack Alert Program (NHAAP) ⁽⁴⁾ summarizes the clinical information needed to make the diagnosis of possible ACS at the earliest phase of clinical evaluation (Table 1). The implication of this early diagnosis for clinical management is that a patient who is considered to have an ACS should be placed in an environment with continuous electrocardiographic (ECG) monitoring and defibrillation capability, where a 12-lead ECG can be obtained expeditiously and definitively interpreted within 10 min. The most urgent priority of early evaluation is to identify patients with AMI who should be considered for immediate reperfusion therapy and to recognize other potentially catastrophic causes of sudden patient decompensation, such as aortic dissection.

Patients diagnosed as having an AMI suitable for reperfusion (with ST-segment elevation) are excluded from management according to these guidelines and should be managed as indicated according to the ACC/AHA Guidelines for the Management of Patients With Acute Myocardial Infarction ⁽⁵⁾. The management of patients who experience periprocedural myocardial damage that is reflected in release of the MB isoenzyme of creatine phosphokinase (CK-MB) also is not considered here. Patients with AMI and with definite ischemic ECG changes who are not suitable for acute reperfusion should be diagnosed and managed as patients with UA. The residual group of patients with an initial diagnosis of ACS will include many patients who will ultimately be proven to have a noncardiac cause for the initial clinical presentation that was suggestive of ACS. Therefore, at the conclusion of the initial evaluation, which is frequently carried out in the ED but sometimes occurs during the initial hours of inpatient hospitalization, each patient should have a provisional diagnosis of 1) ACS, which in turn is classified as a) ST-segment elevation MI (STEMI), a condition for which immediate reperfusion therapy (thrombolysis or percutaneous coronary intervention [PCI]) should be considered; b) NSTEMI; or c) UA; 2) a non-ACS cardiovascular condition (e.g., acute pericarditis); 3) a noncardiac condition with another specific disease (e.g., chest pain secondary to esophageal spasm); and 4) a noncardiac condition that is undefined. In addition, the initial evaluation should be used to determine risk and to treat life-threatening events.

In these guidelines, UA and NSTEMI are considered to be closely related conditions whose pathogenesis and clinical presentations are similar but of differing severity; that is, they differ primarily in whether the ischemia is severe enough to cause sufficient myocardial damage to release detectable quantities of a marker of myocardial injury, most commonly troponin I (TnI), troponin T (TnT), or CK-MB. Once it has been established that no biochemical marker of myocardial necrosis has been released (with a reference limit of the 99th percentile of the normal population) ⁽⁶⁾, the patient with ACS may be considered to have experienced UA, whereas the diagnosis of NSTEMI is established if a marker has been released. In the latter condition, ECG ST-segment or T-wave changes may be persistent, whereas they may or may not occur in patients with UA, and if they do, they are usually transient. Markers of myocardial injury may be detected in the bloodstream hours after the onset of ischemic chest pain, which allows the differentiation between UA (i.e., no markers in circulation; usually transient, if any, ECG changes of ischemia) and NSTEMI (i.e., elevated biochemical markers). Thus, at the time of presentation, patients with UA and NSTEMI may be indistinguishable and therefore are considered together in these guidelines.

2. Pathogenesis of UA/NSTEMI
These conditions are characterized by an imbalance between myocardial oxygen supply and demand. They are not specific disease such as pneumococcal pneumonia, but rather a syndrome, analogous to hypertension. Five nonexclusive causes are recognized ⁽⁷⁾ (Table 2).

With the first 4 causes, the imbalance is caused primarily by a reduction in oxygen supply to the myocardium, whereas with the fifth cause, the imbalance is due principally to increased myocardial oxygen requirements, usually in the presence of a fixed restricted oxygen supply.

• The most common cause of UA/NSTEMI is reduced myocardial perfusion that results from coronary artery narrowing caused by a nonocclusive thrombus that developed on a disrupted atherosclerotic plaque and is usually nonocclusive. Microembolization of platelet aggregates and components of the disrupted plaque is believed to be responsible for the release of myocardial markers in many of these patients.
• A less common cause is dynamic obstruction, which may be caused by intense focal spasm of a segment of an epicardial coronary artery (Prinzmetal's angina) (see Section VI. F). This local spasm is caused by hypercontractility of vascular smooth muscle and/or by endothelial dysfunction. Dynamic coronary obstruction can also be caused by the abnormal constriction of small intramural resistance vessels.
• A third cause of UA is severe narrowing without spasm or thrombus. This occurs in some patients with progressive atherosclerosis or with restenosis after a PCI.
• The fourth cause is arterial inflammation, perhaps caused by or related to infection, which may be responsible for arterial narrowing, plaque destabilization, rupture, and thrombogenesis. Activated macrophages and T-lymphocytes located at the shoulder of a plaque increase the expression of enzymes such as metalloproteinases that may cause thinning and disruption of the plaque, which in turn may lead to UA/NSTEMI.
• The fifth cause is secondary UA, in which the precipitating condition is extrinsic to the coronary arterial bed. These patients have underlying coronary atherosclerotic narrowing that limits myocardial perfusion, and they often have chronic stable angina. Secondary UA is precipitated by conditions that 1) increase myocardial oxygen requirements, such as fever, tachycardia, and thyrotoxicosis; 2) reduce coronary blood flow, such as hypotension; or 3) reduce myocardial oxygen delivery, such as anemia or hypoxemia.

These 5 causes of UA/NSTEMI are not mutually exclusive (Figure 2).

3. Presentations of UA
There are 3 principal presentations of UA: 1) rest angina (angina commencing when the patient is at rest), 2) new-onset severe angina, and 3) increasing angina (Table 3) ⁽⁸⁾. Criteria for the diagnosis of UA are based on the duration and intensity of angina as graded according to the Canadian Cardiovascular Society (CCS) classification (Table 4) ⁽⁹⁾.

The strictness of the criteria used to define UA/NSTEMI, the rigor used in consistent application of these criteria, and the presence of comorbid conditions all greatly influence reported mortality rates. Published series commonly include only patients for whom a definitive diagnosis of UA has been established and do not include all patients from the time of onset of symptoms. Therefore, mortality rates observed in any series of carefully defined patients with UA/NSTEMI will tend to understate the risk. Data that depict survival rates and survival rates without MI, obtained from 1 large trial ⁽¹⁰⁾ carried out with patients with UA/NSTEMI, indicate that the risk associated with an ACS is greatest during the first 30 days after presentation and thereafter stabilizes at a lower rate (Figure 3).