2 Guideline: Initial Evaluation and Treatment of Unstable Angina Introduction Patients with symptoms suggestive of unstable angina present to medical attention either by a telephone call to a medical provider, by a visit to a medical facility, or by emergency transport. The medical provider must appropriately match the intensity and urgency of care with the severity of presenting symptoms. Chapter 1 described the criteria by which clinicians can judge whether a patient's presenting symptoms are consistent with unstable angina and assess the short-term risk of the condition as high, intermediate, or low risk for cardiac events. This chapter describes the initial evaluation and management of patients with unstable angina. Figure 3 depicts the decision logic used to identify patients appropriate to manage using recommendations presented in this guideline. Objectives of Care Stabilization of acutely ill patients is the most urgent initial objective. However, for the majority of patients presenting with symptoms suggestive of unstable angina who are obviously stable, triage to the appropriate care environment is the most important early task. A pressing question influencing early care is whether the patient is having an acute MI and has indications for thrombolytic or other reperfusion therapy. During the initial evaluation, until it is clear that high-risk characteristics are not present, it is reasonable to address stabilization and triage of all patients as if they were in a high-risk category. For all patients, anti-ischemic therapy should be instituted promptly in the ED as soon as a working diagnosis of unstable angina is established. Therapy should be directed toward relieving symptoms and stabilizing the patient by preventing ischemic complications, particularly recurrent unstable angina or acute MI. As the situation permits, the patient should be moved from the ED to the most appropriate environment to monitor complications and minimize psychological stress and cardiac work. However, initial medical therapy in the ED should not be delayed while triage arrangements are made. Patients initially considered to have unstable angina but subsequently found to have an alternate diagnosis should be excluded from further management by this guideline at the time the alternate diagnosis is made. Approach to Care Objectives Entry into Medical Care Directed by the Guideline Telephone Presentation. Recommendation: Because both clinical examination and ECG are critical to early risk assessment, the initial evaluation of the patient with symptoms suggesting possible unstable angina should be done by a medical practitioner in a facility equipped to perform an ECG and not over the telephone (strength of evidence = B). Health practitioners frequently receive calls from patients who are concerned that the symptoms they notice reflect heart disease. Patients with severe and increasing angina or other symptoms suggesting an impending cardiac catastrophe should be urged to seek transport to an ED. More commonly, telephone calls describe situations that are not clearly urgent, and both the patient and the practitioner often have difficulty knowing which symptoms can be ignored or explored as a nonemergent problem and which should receive more immediate attention. Patients with known CAD-including those with a recent MI, CABG, or PTCA-who contact their physician because of exacerbation or recurrence of symptoms should, in most instances, be encouraged to seek direct medical care. Only those patients who have been recently evaluated and who are calling for advice regarding modification of medication as part of an ongoing treatment plan represent exceptions to this principle. Most telephone calls from patients without known CAD regarding chest discomfort of possible cardiac origin do not represent an emergent situation but simply reflect the desire of the patient for reassurance about the absence of disease or the safety of the symptoms described even if coronary disease might later be found to be present. Despite this fact, nonemergent patients seeking telephone advice for possible cardiac symptoms should be advised that recognition of CAD and evaluation of its severity generally cannot be adequately done by telephone because of the need for an ECG. The importance of an ECG in early evaluation of unstable angina was emphasized in a study of 90 patients with unstable angina that documented ST-segment deviation >1 mm in two or more leads on ECG to have a positive predictive value for adverse clinical events of 79 percent and a negative predictive value of 64 percent in early evaluation of unstable angina (Cohen, Hawkins, Greenberg et al., 1991). In a study by the Research Group on Instability in CAD in Southeast Sweden (RISC), an abnormal initial ECG was found to be present in 55 percent of 911 men at the time of ICU admission, and ST-segment abnormality was found to be predictive of 76 percent of subsequent death or MI events observed in the population after 90-day followup (Nyman, Areskog, Areskog et al., 1993). Patients must retain the ultimate responsibility of deciding whether they will seek medical attention and if so in what environment. A medical practitioner cannot be expected to assume responsibility for a patient with a potentially severe cardiac condition who does not present for direct evaluation. Practitioners should be cautious not to provide inappropriate reassurance to patients inclined not to seek further medical attention. However, medical practitioners may assist by providing information patients may use to decide the degree of urgency with which to seek care. The Patient and Family Guide, Managing Unstable Angina, is a good source of this information, and this companion booklet, which was developed in conjunction with this guideline, is available free of charge from the AHCPR. Outpatient Facility or Emergency Presentation. Recommendation: Patients with suspected unstable angina who have a symptom duration >20 minutes, hemodynamic instability, or recent loss of consciousness should generally be referred to an ED. Other patients with suspected unstable angina may be seen initially either in an ED or in an outpatient facility at the discretion of the attending physician (strength of evidence = C). The decision about where to perform the initial patient evaluation must be based on the individual patient's presenting complaint and circumstances, the options for transportation, and the local facilities available. In general, patients with unremitting symptoms >20 minutes in duration, with symptoms suggesting acute or worsening congestive heart failure (CHF), such as increasing dyspnea or orthopnea, and those with syncope or near-syncope, should be encouraged to go to (or be transported to) an ED. Transport of these patients by emergency medical transport teams is preferable when readily available. Transport as a passenger in a private vehicle is an acceptable alternative if waiting for an emergency vehicle would impose a long delay. All other patients may be seen initially in an outpatient facility mutually agreeable to the patient and physician. The first 10 to 20 minutes of the initial encounter with the patient should include a brief assessment of the urgency with which evaluation must be done and treatment started. The urgency of evaluation for patients with ongoing rest pain upon presentation is substantially greater than for patients whose symptoms have already resolved. If the patient is hemodynamically stable and does not appear in great distress, the initial evaluation can precede treatment decisions. Otherwise, both must be done simultaneously. Diagnosis of hemodynamic instability is based on the patient's systolic blood pressure (SBP) (i.e., <=90 mmHg), respiratory status (i.e., acutely dyspneic), mental state (i.e., confused or obtunded), and peripheral circulation (i.e., vasoconstricted, diaphoretic). No data are available prospectively comparing outcomes of patients treated in different initial care environments and grouped by the severity of presenting cardiac symptoms. Studies of disposition of patient groups after ED presentation for complaints of possible cardiac etiology suggest practitioners must identify the minority of patients with potentially severe disease from within the much larger group of patients who either have no CAD or at least no need for urgent care. In one study of more than 12,140 patients presenting to EDs of three university and four community hospitals for evaluation requiring consideration of acute IHD, noncardiac chest pain was diagnosed in about 65 percent (White, Lee, Cook et al., 1990). Even in the most urgent subgroup of patients presenting with acute-onset cardiac disorders, time is usually adequate to transport patients to an environment where they can undergo evaluation and treatment (Ghali, Cooper, Kowatly et al., 1993;Schroeder, Lamb, and Hu, 1977). A large study of consecutive patients transported to the ED by ambulance for chest pain suspected to be of cardiac etiology resulted in a final diagnosis of acute MI in about one-third, unstable angina in one-third, and noncardiac etiology in most of the remaining third of this population. Only 1.5 percent of these patients developed cardiopulmonary arrest in the prehospital or ED settings (Hargarten, Chapman, Stueven et al., 1990). These data suggest that patients with acute chest pain are better served by transport to an adequate ED than by compromising the quality of the care environment in an attempt to shorten the initial transport time. Stabilization and Initial Evaluation Initial Evaluation of Low- and Intermediate-Risk Patients. Intermediate- and low-risk patients (see Table 8) who arrive at a medical facility in a pain-free state, have unchanged or normal ECGs, and are hemodynamically stable represent more of a diagnostic than an urgent therapeutic challenge. Evaluation begins in these patients by obtaining information from history, physical examination, and ECG to be used to confirm the diagnosis of unstable angina as discussed in Chapter 1. After this initial evaluation, those patients assigned to the definitely not angina category are excluded from further management by this guideline. These excluded patients should be evaluated further for another cause of their symptoms or reassured that their symptoms are likely to be self-limited if a nonthreatening cause has been identified (e.g., anxiety, musculoskeletal pain). Reassurance should be balanced with instructions to return for further evaluation if symptoms worsen or fail to respond to symptomatic medical treatment. Patients meeting criteria for unstable angina should receive ASA therapy, 160 to 324 mg, as described below, unless contraindications are present. Patients without pain but with definite ischemic ECG changes should be treated during this initial phase as if they have ongoing pain. Patients without ongoing pain or ischemic ECG changes should be further risk-stratified. About one-half of these patients will be known to have CAD for which they have received prior treatment. Management decisions for these patients with known CAD are similar to those for patients without known CAD but with a high likelihood of having CAD. Details of past medical care most likely to impact on current management decisions include prior assessments of LV function and coronary anatomy, prior revascularization procedures, and recent medication history. The current historic information of greatest importance in these patients is their assessment of the severity and tempo of their symptoms in the context of their prior history. Patients who feel that their symptoms are similar to those experienced during a prior major cardiac event and patients who have undergone coronary angioplasty or a bypass operation within the past year and have intermediate- or high-risk features deserve hospital admission for more thorough evaluation in most cases. Patients with known LV dysfunction or CHF represent another group that should usually be admitted to the hospital. Patients who are at or near maximal medical treatment and who have been symptomatic over the preceding 24 hours deserve hospital admission. Others who should be admitted include patients with a symptom duration >=1 hour (even without ECG changes), patients with a history of rest pain lasting >20 minutes within the past week, or patients with a two-class worsening of angina (Goldman, Cook, Brand et al., 1988). All low-risk patients with known CAD usually can be managed as described in Chapter 3. Hospitalization may be reasonable in some low-risk patients with known CAD, such as those with other diseases that might confound outpatient management and patients who live in areas remote from an appropriate health care facility. Patients without known CAD and a high likelihood of CAD are managed initially as if they have high-risk unstable angina. For all other patients without known CAD, the pattern of recent symptoms defines the urgency with which further evaluation should proceed to determine the likelihood of CAD as a cause of symptoms. Patients with an intermediate likelihood of CAD for whom another cause of current symptoms cannot be determined who also appear to be at intermediate risk are usually best managed by hospitalization in a standard or intermediate care bed. Patients with an intermediate likelihood of CAD but low risk deserve further evaluation for the cause of their symptoms. In some cases, it will be logistically reasonable to proceed with a more definitive evaluation in the ED. Alternatively, patients who have been asymptomatic for >24 hours can reasonably be referred to an outpatient facility for definitive workup. However, in most situations, this evaluation should be completed within 72 hours, and patients should always be advised to return to the ED immediately for reevaluation if symptoms recur, worsen, or fail to respond to prescribed symptomatic therapy. A trial of sublingual NTG may provide useful diagnostic information in some of these patients. All patients should be instructed to observe and later report the influence of medication and activity on symptoms experienced during the interval prior to more definitive evaluation. Patients with a low likelihood of CAD, especially those with a history of intermediate-risk features who currently do not have ongoing pain, ECG change, or hemodynamic instability, should be evaluated carefully for other causes of the presentation including: musculoskeletal chest pain; gastrointestinal (GI) disorders, such as gastritis, peptic ulcer disease, or cholecystitis; intrathoracic disease, such as esophageal spasm, pneumonia, pleurisy, pneumothorax, or pericarditis; neuropsychiatric disease, such as hyperventilation; or panic disorder. Patients who are found to have evidence of one of these alternative diagnoses should be excluded from management by this guideline and referred appropriately for followup care. Stable angina may also be diagnosed in this setting, and patients with this diagnosis are excluded from further management by this guideline. Patients for whom a specific diagnosis cannot be made on the brief initial examination should undergo a more definitive evaluation. This evaluation may proceed in the ED or outpatient facility if time permits. Occasionally, admission to a standard hospital unit is required for definitive evaluation of patients with complex presentations. Definitive evaluation of patients with a low likelihood of CAD and low risk is less urgent than it is for patients at higher risk. If time is not adequate in the ED setting to evaluate these low-risk patients sufficiently to arrive at an alternate diagnosis or to differentiate unstable angina from stable angina, patients should be referred for outpatient evaluation, generally within 72 hours, as described in Chapter 3. Evaluation of Unstable Angina Patients for Precipitating Noncardiac Causes of Symptoms. Recommendation: The definitive initial evaluation of the unstable angina patient should include a systematic search for precipitating noncardiac causes that might explain the new development of unstable symptoms or the conversion from a stable to an unstable course. Thus, each patient's ECG should be evaluated for arrhythmias, and patients should have a measurement of body temperature and blood pressure, a hemoglobin or hematocrit determination, and a physical examination for evidence of other cardiac diseases (particularly aortic valve disease and hypertrophic cardiomyopathy) or hyperthyroidism (exophthalmos, resting tremor, thyroid exam). Review of the history may reveal additional potential exacerbating factors such as a recent increase in physical activity level especially in combination with environmental temperature extremes, noncompliance with medical therapy, or a recent increase in psychological stress levels (strength of evidence = C). Information from the initial history, physical examination, and ECG will enable the practitioner to recognize and exclude patients classified as "not angina." The remaining patients should undergo more complete evaluation for secondary causes of the presentation and for manifestations of coexisting diseases that might alter management. Cardiac disorders other than CAD that may present with acute ischemia, particularly in the setting of significant CAD, include aortic stenosis and hypertrophic cardiomyopathy. Factors that increase the oxygen demand or decrease myocardial oxygen delivery to the heart may provoke or exacerbate ischemia, particularly in the presence of significant CAD. Previously unrecognized gastrointestinal bleeding is one common secondary cause of exacerbated CAD symptoms due to anemia. Acute worsening of chronic obstructive lung disease (with or without superimposed infection) may lower oxygen saturation levels enough to worsen CAD symptoms. Evidence of increased cardiac oxygen demand over normal resting levels can be judged from the presence of a fever or findings of hyperthyroidism. Similarly, uncontrolled hypertension can increase oxygen demand by making the heart work harder to eject blood during each systole (increased afterload). Sustained supraventricular or ventricular tachycardias may also provoke acute ischemic symptoms. Initial Evaluation of High-Risk Patients. Recommendation: The initial assessment of the high-risk patient with possible unstable angina must start with a rapid evaluation of the probability of immediate adverse outcomes and the need for emergency diagnostic and therapeutic interventions. Patients with ongoing symptoms, hemodynamic instability, or recent loss of consciousness should have a directed history, physical examination, and 12-lead ECG completed within 20 minutes of arrival to a medical facility (strength of evidence = B). Specific diagnoses that must be explicitly considered are acute MI meeting criteria for reperfusion therapy, aortic dissection, leaking or ruptured thoracic aneurysm, pericarditis with tamponade, pneumothorax, and pulmonary embolism. Other noncardiovascular diagnoses may need to be considered as well, depending on initial findings (strength of evidence = B). Patients who have ongoing symptoms of unstable angina at rest when first seen deserve more urgent evaluation than patients with prior discomfort who are asymptomatic when first seen. Intensive medical treatment, as described in Chapter 4, should begin immediately in the ED in patients with ongoing rest pain or definite ECG ischemia and should continue as the patient is transported to the definitive care environment. Ongoing rest pain with treatment should drive initial evaluation at a more urgent pace and therapy to more aggressive regimens than is required for patients with pain that resolves rapidly as treatment is begun. Occasionally, patients with rest angina also have hemodynamic instability manifested by hypotension, dyspnea, and/or a sense of impending catastrophe. Patients who appear unstable should have simultaneous evaluation and treatment. IV access can be obtained while a brief cardiovascular history and physical examination are completed and an ECG is taken. When initial blood work is obtained, a sample should be sent for determination of creatinine kinase (CK). Medical personnel trained in cardiopulmonary resuscitation should remain in close attendance during the period of initial stabilization. Oxygen should be administered by mask or nasal cannula. A record review of 445 patients presenting to 10 metropolitan EDs for management of acute nontraumatic chest pain found 78 percent of patients underwent physician evaluation and 60 percent had an initial ECG within 20 minutes of arrival in the ED (Heston and Lewis, 1992). This unselected population included patients presenting with a spectrum of severity. It is, therefore, reasonable that all patients presenting with severe symptoms be evaluated for risk within 20 minutes of arrival at the ED. In ED environments without a physician continuously present, nurses or other medical providers should assess the patient, obtain an ECG, and begin treatment to support any patient with hemodynamic instability and involve the physician in important decisions using telecommunications as appropriate to the specific circumstances occurring before the arrival of the physician in the ED. As treatment is begun in patients with the presumptive diagnosis of high-risk unstable angina, further evaluation should continue to address other possible conditions as alternate diagnoses to unstable angina. Other severe conditions to be considered include acute MI, aortic dissection, leaking or ruptured thoracic aneurysm, acute pericarditis with tamponade, pulmonary embolism, pneumothorax, esophageal rupture, or rupture or ischemia of intra-abdominal organs. Chest or abdominal images (chest radiograph, transthoracic or transesophageal echocardiogram, computed tomogram, or magnetic resonance image) may be useful for differentiating these severe conditions from unstable angina at this early stage of evaluation. However, a history and physical examination directed by suspicion of one of these conditions remains the most important diagnostic tool. In one study of 918 consecutive patients evaluated for suspicion of unstable angina, common alternate final diagnoses included unspecified chest pain, pulmonary embolism, acute abdominal disease, and other miscellaneous diseases (Aase, Jonsbu, Liestol et al., 1993). Initial Treatment of Patients with Unstable Angina Initial General Care. Recommendation: Patients with unstable angina and ongoing rest pain should be placed at bed rest during the initial phase of medical stabilization (strength of evidence = C). Recommendation: Patients with obvious cyanosis, respiratory distress, or high-risk features (see Table 8) should receive supplemental oxygen. A finger pulse oximetry or arterial blood gas determination should be used to confirm adequate arterial oxygen saturation and continued need for supplemental oxygen (strength of evidence = C). Recommendation: As soon as the diagnosis of unstable angina is made, patients should be placed on continuous ECG monitoring for ischemia and arrhythmia detection (strength of evidence = C). The severity of symptoms of unstable angina will dictate some of the general patient care that should be employed during initial treatment of patients with a diagnosis of unstable angina. Patients should be placed on bed rest while ischemia is ongoing but can be mobilized to a chair and bedside commode once they become symptom-free. Subsequent activity restriction should be focused on preventing recurrent symptoms and may be liberalized as judged appropriate as patients respond to treatment. Patients with cyanosis, respiratory distress, or high-risk features (see Table 8) should receive supplemental oxygen, and adequate blood arterial saturation should be confirmed by direct measurement or pulse oximetry. No evidence is available to support the common medical practice of administering oxygen to all patients with acute chest pain syndromes in the absence of signs of respiratory distress. Although routine use of oxygen during initial evaluation would not appear to cause much harm, more selective use of oxygen for patients with questionable respiratory status or those with documented hypoxemia by finger pulse oximeter is a preferable strategy. All patients with unstable angina should undergo cardiac monitoring during their ED evaluation. Initial Pharmacologic Treatment. [1] Drugs to be considered for use at the time of initial evaluation and treatment of patients with symptoms suggestive of unstable angina include ASA, heparin, nitrates, and beta blockers. The certainty of diagnosis, severity of symptoms, hemodynamic state and medication history will determine the choice and timing of drugs used in individual patients. Treatment with an indicated drug should begin in the ED and not be delayed until hospital admission. The aggressiveness of drug dosage will depend on the severity of symptoms and, for many drugs, will require modification throughout the subsequent hospital course. Principles of drug use are not altered by the care environment in which the drug is administered. To avoid redundancy, a detailed description of the use of each drug will be presented only once in this guideline, although modifications of drug use required during other phases of care will be mentioned when appropriate. Because ASA and heparin are the drugs that should be considered early in the treatment of unstable angina, their use is described in this chapter. Nitrates, beta blockers and narcotics are often begun in the ED, but their use at maximum dosage and the importance of response to these agents for determining the need for alternate therapies in individual patients often occurs in the intensive care environment. For this reason the use of nitrates, beta blockers, and morphine is discussed in detail in Chapter 4. Table 9 summarizes indications, contraindications, and usual dosage of drugs commonly used in the ED to treat patients with unstable angina. Recommendation: IV thrombolytic therapy is not indicated in patients who do not have evidence of acute ST-segment elevation or left bundle branch block (LBBB) on their 12-lead ECG (strength of evidence = A). [1]Some of the recommendations in this guideline suggest the use of agents for purposes or in doses other than those specified by the Food and Drug Administration (FDA). Such recommendations are made after consideration of concerns regarding nonapproved indications. Where made, such recommendations are based on more recent clinical trials or expert consensus. The failure of IV thrombolytic therapy to improve clinical outcomes in the absence of acute MI with ST-segment elevation or LBBB has now been clearly demonstrated (TIMI IIIA, 1993;TIMI IIIB, in press). A meta-analysis by Duke University staff of recent studies of thrombolytic therapy in unstable angina patients shows no benefit of thrombolysis versus standard therapy for the reduction of acute MI. Thrombolytic agents had no significant effect and actually increased the risk of MI by 1.7 percent (95% confidence interval [CI] 2.4-5.8%) (Figure 4 ). Consequently, such therapy is not recommended for unstable angina patients managed according to this guideline. The distinction between unstable angina and acute MI often cannot be definitively made during the initial evaluation. Patients with ECG changes diagnostic of epicardial injury (i.e., >=1 mm ST-elevation in two or more contiguous leads, or ST-depression in V1-V3) or LBBB with a consistent history should be managed as if they have an acute MI, including prompt administration of ASA, beta blockers, and reperfusion therapy. In most large trials of reperfusion therapy, such patients have a >=95 percent prevalence of acute MI. In the Multicenter Chest Pain Study, however, only about 80 percent of patients meeting these criteria had acute MI (Lee, Weisberg, Brand et al., 1989). Recommendation: All patients with the diagnosis of unstable angina should receive regular ASA 160 to 324 mg as soon as possible after presentation unless a definite contraindication is present, such as evidence of ongoing major or life-threatening hemorrhage, a significant predisposition to such hemorrhage (e.g., recent bleeding peptic ulcer disease), or a clear history of severe hypersensitivity to ASA (strength of evidence = A). The recommendation for an initial ASA to be given in the ED is based on the efficacy of this therapy in independently reducing mortality in patients with acute MI enrolled in the second International Study of Infarct Survival (ISIS-2) trial (1988). Those data, combined with the recognition that a definitive distinction between acute MI and unstable angina is frequently not possible at the time of acute presentation, led to the recommendation to initiate ASA immediately in appropriate patients. No randomized trials or other studies compare immediate with a more delayed initiation of ASA in unstable angina. Some of the strongest evidence available about the long-term prognostic effects of medical therapy on coronary disease outcomes pertains to ASA. ASA inhibits the formation of thromboxane A2, thereby diminishing platelet aggregation promoted by some but not all physiologic stimuli. Since platelets are one of the main participants in the thrombotic consequences of disruption of a coronary plaque, platelet inhibition is a plausible mechanism for clinical benefit. In unstable angina, ASA has been shown to have significant benefit for stabilizing an acutely unstable coronary plaque, producing reductions in mortality and MI rates of 50 percent or more. Four randomized trials clearly demonstrated the benefit of ASA in the long-term treatment of unstable angina. The Veterans Administration (VA) Cooperative Study Group in 1983 compared the effects of 324 mg of ASA given once a day for 12 weeks with the effects of placebo in 1,266 male veterans admitted with unstable angina (Lewis, Davis, Archibald et al., 1983). At the conclusion of the 12-week study period, there was a 51 percent reduction in the rate of nonfatal acute MI in the ASA group (3.4% vs. 6.9%, p=0.005) and a 51 percent reduction in the rate of death or acute MI in the ASA group (5% vs. 10.1%, p=0.0005). Although the difference in the mortality rates of the ASA and placebo groups was not significant at 12 weeks, there was a significant 43 percent reduction in the mortality rate of the ASA-treated group at 1-year followup (5.5% vs. 9.6%, p=0.008). A group of Swedish investigators reported the effects of ASA (75 mg/day) compared with the effects of placebo in 796 men admitted with either unstable angina or non-Q-wave MI (Wallentin, 1991). Study treatment had been scheduled for 1 year, but the trial was stopped after publication of the ISIS-2 trial. All patients received at least 3 months of treatment. At 12-month followup, there was a significant 48 percent reduction in the combined rate of death and MI in the ASA group (11% vs. 21%, p=<0.0001). However, there was no significant difference in the risk of death alone (2.7% vs. 4.5%, p=NS). ASA also reduced the incidence of recurrent angina in this trial. A Canadian multicenter trial reported in 1985 tested the effects of 325 mg of ASA given every 6 hours with the effects of placebo in 555 patients admitted to the CCU with unstable angina (Cairns Gent, Singer et al., 1985). At an average followup point of 18 months, there was a significant 56 percent reduction in the risk of cardiac death (5% vs. 9.4%, p=0.009), although there was no difference in the followup rate of MI. A second Canadian study reported in 1988 examined the effects of 325 mg of ASA given twice per day versus those of placebo in 479 patients admitted to the CCU with unstable angina (Theroux, Ouimet, McCans et al., 1988). The researchers reported a 28 percent reduction in the rate of MI over the first week of therapy in the ASA group (3.3% vs. 11.9%, p=0.012). There were too few deaths to analyze the effects of the treatment on this endpoint. Meta-analysis of these four studies to assess outcomes measured at greater than 3 months suggests that ASA reduces the risk of MI by 48 percent and the risk of death by 51 percent. There was a 47 percent reduction in the combined risk of death and MI as illustrated in the likelihood function in Figure 5 . No data directly compare the efficacy of different doses of ASA in patients presenting with unstable angina. However, a broad review and meta-analysis of different doses of ASA in long-term treatment of patients with CAD suggest equal efficacy of daily doses of 75-324 mg per day (Antiplatelet Trialists' Collaboration, 1994). It appears reasonable to initiate ASA treatment in patients with unstable angina with a dose of at least 160 mg as used in the ISIS-2 (1988) trial. Thereafter, an ASA dose of 80-324 mg could be used for long-term therapy. Recommendation: IV heparin should be started as soon as a diagnosis of intermediate- or high-risk unstable angina is made (strength of evidence = A). The initial dose is 80 units/kg by IV bolus followed by a constant infusion of 18 units/kg/hr, maintaining the activated partial thromboplastin time (aPTT) at 1.5 to 2.5 times control. There is clear and compelling evidence that IV heparin started early in the course of unstable angina reduces the risk of subsequent MI and recurrent unstable angina. Heparin exerts its anticoagulant effect by markedly accelerating the action of circulating antithrombin III, a proteolytic enzyme that inhibits thrombin and several other activated factors in the clotting cascade. Thus, heparin acts to prevent thrombus propagation but does not lyse existing thrombi (Hirsh, 1991). Five randomized trials of heparin use in unstable angina have been reported. Two early trials showed a benefit but must be judged inconclusive due to methodologic defects (Telford and Wilson, 1981;Williams, Kirby, McPherson et al., 1986). A group of Swedish investigators performed a double-blind placebo-controlled trial with a 2x2 factorial design in 796 men with unstable angina or non-Q-wave infarction (RISC Group, 1990). The active drug regimens tested were ASA 75 mg daily for >=3 months and heparin 5,000 units IV bolus every 4 hours. Drug therapy was initiated 1 to 3 days after hospital admission. This investigation did not demonstrate any therapeutic benefit of heparin alone, although patients treated with heparin and ASA combined had significantly fewer (p=0.0007) deaths and MIs than those treated with heparin alone, and fewer, but not significantly fewer, cardiac events than ASA alone (RISC Group, 1990). Two placebo-controlled heparin and ASA trials were performed at the Montreal Heart Institute. A 479-patient study performed between 1986 and 1988 tested treatments consisting of 650 mg of ASA immediately followed by 324 mg twice per day and a 5,000-unit IV heparin bolus followed by 1,000 units per hour in a 2x2 factorial design (Theroux, Ouimet, McCans et al., 1988). Importantly, a double-blind placebo was used for both heparin and ASA ensuring truly unbiased assessment of efficacy. Although the study was too small to detect an effect on mortality, the risk of MI was reduced by 89 percent and the risk of recurrent refractory angina by 63 percent relative to placebo. In this study, ASA also reduced the rate of MI, but the two drugs given together were not superior to heparin alone (possibly due to the relatively small sample size and inadequate statistical power) and were associated with a slightly higher risk of serious bleeding. A more recent double-blind randomized trial from this group compared ASA (325 mg twice per day) and heparin (5,000 units IV bolus followed by a constant infusion titrated to an aPTT 1.5 to 2.5 3 control) in 484 unstable angina patients. MI (fatal or nonfatal) occurred in 0.8 percent of heparin patients and 3.7 percent of ASA patients (p=0.035). This trial was the first to clearly demonstrate the superiority of IV heparin over ASA in the acute phase of unstable angina (Theroux, Waters, Qiu et al, 1993). Taken together, these available trials indicate a substantial reduction in acute MI incidence from early heparin, with possible reduction of death and recurrent unstable angina. No direct data exist about the relative efficacy of bolus administration versus continuous infusion of heparin, but two randomized trials from another area of medicine suggest equivalent anticoagulant results and more bleeding complications with intermittent therapy. Thus, although continuous infusion is preferred in this guideline, centers not equipped to administer heparin by continuous infusion may substitute a regimen of 5,000 units IV bolus every 4 hours. The efficacy of ASA and heparin in combination is suggested, but this benefit has not been unequivocally demonstrated relative to monotherapy by their complementary mechanisms of action and demonstrated value in different phases of the disease. ASA has been shown to provide benefits with an initial ED dose in patients who are later confirmed to have the diagnosis of acute MI. ASA may also prevent reactivation of acute IHD when heparin therapy is discontinued later in the hospital course. Finally, ASA has demonstrated efficacy in long-term secondary prevention. Heparin, on the other hand, is the most efficacious agent available to reduce early in-hospital ischemic events. Thus, the combination of the two agents for initial therapy in unstable angina is strongly recommended. Treatment and Assessment of Relief of Symptomatic Ischemia Treatment of Symptomatic Ischemia. Recommendation: Anti-ischemia medication should be begun and titrated to dosages that are adequate to relieve symptomatic ischemia without excessive bradycardia or hypotension. Patients should be encouraged to participate in monitoring the success of medication in relieving their pain. Use of a 10-point numerical pain rating scale, visual analog scale, or adjective rating scale is suggested to help them describe the intensity of pain (strength of evidence = C). Relief of symptoms of unstable angina is attempted in the ED with beta blockers and nitrates. If oral and sublingual administration of these agents does not relieve ischemia, IV use is indicated. Morphine sulfate is used when these measures are ineffective and can also be helpful during the initial stages of therapy while these other agents are being titrated up to target doses. After initial symptom control is achieved, any recurrent ischemic symptoms should prompt performance of an urgent ECG with the goal of obtaining a recording during symptoms. Calcium channel blockers are reserved for patients requiring an additional agent beyond nitrates and beta blockers and for patients with variant angina. The detailed rationale and mode of use for each of these agents are presented in Chapter 4. Patients who are counseled on the goal of relief of ischemic symptoms can assist greatly in monitoring effectiveness of therapy by accurately reporting changes in pain intensity. Patients with well-developed coping skills may underreport their pain. In addition, some patients believe that because they are ill, they should expect to feel some pain. These patients often receive less medication than they need to control their anginal symptoms. Use of an objective scale aids in assessment of efficiency of treatment to relieve pain and ischemia. The 10-point individual patient-based intensity score grades pain in severity ranging from 1 being barely perceptible to 10 being the most severe pain ever experienced (Scott and Huskisson, 1976;Sriwatanakul, Kelvie, Lasagna et al., 1983). Assessment of the Relief of Ischemia. A vast majority of patients who present with signs of ischemia at rest stabilize rapidly and have decreasing or absent chest pain after 30 minutes of aggressive medical management. These patients should be admitted to an ICU or intermediate care unit. Failure to respond to initial therapy should prompt reconsideration of other possible catastrophic causes of chest pain including ongoing acute MI, aortic dissection, pulmonary embolism, pneumothorax, esophageal rupture, or rupture or ischemia of intra-abdominal organs. Patients considered to have unstable angina after further evaluation who fail to respond within 30 minutes to initial treatment are at increased risk for MI or cardiac death (Gibson, Young, Boden et al., 1987;Larsson, Jonasson, Ringqvist et al., 1992; Silva, Galli, and Campolo, 1993). These patients are best served by care in the ICU of an institution with capabilities to perform intra-aortic balloon pump (IABP) placement, cardiac catheterization, PTCA, and CABG. Transfer may be considered to another institution when ED care has begun in an institution without access to these invasive technologies. The benefits of transfer to a facility providing these options of care must be weighed against the risks. In some cases, such as extremely elderly patients or elderly patients with advanced comorbidity, transfer may be inappropriate and/or not in accordance with the wishes of the patient and his or her family. However, in most situations, prompt transfer of severely ill patients with unstable angina to an institution offering definitive care is the most judicious choice. Where long distances are involved, helicopter transport staffed by cardiovascular specialists may benefit deteriorating patients with unstable angina, but ambulance transport is usually adequate in the absence of signs of hemodynamic instability. In remote regions of the country where transfer is not feasible, care should continue in the most satisfactory environment available. Aggressive pharmacologic treatment should continue during the time interval between the decision for transfer, and the time transfer could occur with the option to abort the transfer if the patient improves sufficiently. Patient Counseling Recommendation: As permitted by the level of urgency, the health care team should inform the patient and the patient's family or advocate of the probable diagnosis, most reasonable treatment strategies, and most likely outcomes at appropriate intervals during initial evaluation and treatment. At the conclusion of this phase, questions and plans for the next phase of care should be addressed (strength of evidence = C). The symptoms of unstable angina often develop abruptly, evoking anxiety and fear in patients. Moreover, the prevalence of cardiac death in our society leads many patients to overestimate the potential threat of their cardiac symptoms, and this fear is reinforced by the obvious concern of health care providers. Many patients will be treated by health care providers they do not know, and others lack knowledge of the health care system and its procedures. Good communication between the patient and health care providers is often hindered by these factors and further reduced by the immediate need of the health care team to diagnose and stabilize the patient. Health care providers must overcome communication barriers and provide the patients timely reassurance and information relating to appropriate management of their condition. Management of patients with unstable angina often requires a decision on the use of alternative tests and procedures with major risks and benefits to patients, and the clinical situation often imposes urgency on reaching these decisions. Obtaining appropriate informed consent is necessary medical practice and is not reiterated at every decision point in this guideline. Patients may be assisted in the difficult task of assimilating and responding appropriately to this information during periods of stress by reiteration of information. The patient may wish to designate a family member or other friend to serve as an advocate for the patient to ensure that the patient understands the information presented by the health care team and to assist in articulating the preferences of the patient. The role of the advocate should not be considered adversarial but should facilitate better communication between care providers and the patient. Communication efforts from health care providers promote a sense of teamwork with the patient and will be rewarded by less anxiety and increased compliance for the patient. Conclusion of Initial Evaluation and Treatment Phase At the conclusion of the initial evaluation and treatment phase, the patient presenting with symptoms suggestive of unstable angina should be assigned to one of four diagnostic categories: 1. Alternate diagnosis, not IHD. 2. Stable angina. 3. Reperfusion-eligible acute MI. 4. Unstable angina. In assigning patients to these groups, the general approach should be to assume that the patient's symptoms are due to CAD until proven otherwise. Patients with a diagnosis other than unstable angina and patients with known CAD who are felt to have symptoms attributable to another cause are managed as indicated by their presumptive diagnoses. Patients with suspected unstable angina, but with symptoms that are not sufficiently severe to meet definitional criteria for unstable angina, are categorized and managed as stable angina. Patients with prolonged (i.e., >20 minutes) chest discomfort and ECG evidence of epicardial injury (ST-segment elevation or ST-segment depression consistent with posterior wall injury) or LBBB are diagnosed and managed as reperfusion-eligible acute MI. All other patients (i.e., those with both unstable angina and acute non-ST-segment elevation MI) should be diagnosed as unstable angina and managed as described in Chapters 3, 4, and 5 of this guideline. Recommendation: High-risk unstable angina patients should be admitted initially to an ICU bed whenever possible (strength of evidence = B). Intermediate-risk unstable angina patients should be admitted to an ICU or monitored cardiac bed (strength of evidence = C). Low-risk unstable angina patients may be managed as outpatients with planned early followup evaluations (strength of evidence = C). Selection of the appropriate environment for further care of patients diagnosed as having unstable angina is determined primarily by assessment of the short-term risk of untoward events. This benefit must be balanced against the extra monetary cost and possibility of complications from needlessly intensive care (Wears, Li, Hernandez et al., 1989). High-risk patients should be admitted to an ICU environment and ideally should be kept there until they have been stabilized and are symptom-free for at least 24 hours or additional prognostic information is obtained (e.g., resting measure of LV function, acute coronary angiography) that indicates they are not as high risk as initially believed. Patients judged intermediate risk may occasionally be managed by careful, intense outpatient care, but more commonly will be admitted to an ICU, intermediate care unit, or monitored hospital bed (Fineberg, Scadden, and Goldman, 1984). At this transition point, intermediate- and high-risk patients should have a basic understanding of what will happen in the next 3 to 6 hours, including knowledge of the identity of the physicians and nurses with primary care responsibility. Low-risk patients who retain the working, but not definite, diagnosis of unstable angina after initial evaluation should undergo additional evaluation as soon as can be arranged but generally no later than 72 hours after initial presentation. Medical Record Information to be entered in the medical record summarizing initial evaluation and management for each patient includes: * Age and sex. * Duration and nature of symptoms prior to presentation. * Previous history of CAD; if yes, prior noninvasive test result, prior cardiac catheterization result, prior myocardial revascularization procedure (bypass or angioplasty). * Medication and drug use. * Risk factors (diabetes, smoking, hypercholesterolemia, hypertension). * Systemic causes for precipitating or exacerbating ischemia. * ECG interpretation. * Initial and final assignment of likelihood of CAD (high, intermediate, low) and basis. * Initial and final risk assignment (high, intermediate, low) and basis. * Summary of other pertinent positive and negative findings. * Major or minor complications of diagnosis or treatment. * Patient counseling, including assessment of patient response. * Disposition for further care. * Deaths classified as noncardiac or cardiac. * Cardiac deaths classified as precipitated by arrhythmia, progressive ischemia, or progressive cardiac failure. Duration of Initial Evaluation and Treatment Phase The initial assessment of whether a patient has unstable angina and which triage option is most suitable generally should be made within the first hour after the patient's arrival at a medical facility. Lack of appropriate hospital beds or transport facilities to move the patient to another medical facility may prevent expedient implementation of the triage decision. In such cases, stabilization and management of ischemic symptoms should continue as if the patient were admitted to the hospital. Patients judged to be low risk at initial evaluation may have completion of their definitive evaluation deferred for up to 72 hours as long as the severity and frequency of symptoms do not worsen. 3 Guideline: Outpatient Care Introduction Patients with unstable angina who are judged in the initial evaluation and treatment phase to be at low risk for adverse outcomes can, in many cases, be safely evaluated further as outpatients. Typically, these are patients who have experienced new onset or worsening symptoms that may be due to ischemia, but they have not had severe, prolonged, or rest episodes in the preceding 2 weeks. Their followup evaluation should have been scheduled as soon as possible, generally 72 hours after the initial presentation. In addition, patients with symptoms suggestive of unstable angina whose presentations are not considered sufficiently urgent to require ED evaluation may be seen first in an outpatient facility. This chapter addresses care of patients presenting for initial evaluation as well as those patients who had initial evaluation in an ED (usually within the past 72 hours) and now present for more definitive evaluation of possible unstable angina (see Figure 6 ). Objectives of Care In patients without known CAD, the three goals of outpatient care are to assess further the cause of the patient's symptoms, evaluate the risk of future adverse cardiac events, and provide adequate symptom relief. In patients with known CAD, the primary concern is whether to intensify medical therapy or consider PTCA or CABG. Approach to Care Objectives Diagnostic Assessment All patients should have a history, physical examination, and ECG. Initial evaluation for patients without prior ED evaluation should proceed as described for low-risk patients in Chapter 2. For patients returning for followup examination of a recent ED visit, the circumstances surrounding the initial presentation and any interval symptoms since the initial examination represent the important features of the history. Evidence of a worsening symptom pattern may necessitate hospital admission for control and further diagnostic workup. This repeat evaluation should also include a further search for factors that might precipitate or exacerbate unstable angina, such as fever, tachyarrhythmias, hyperthyroidism, severe anemia, cocaine use, noncompliance with medical therapy, environmental temperature extremes, severe psychosocial stress, and changes in the level of physical exertion or lifestyle. Patients who develop pain during the clinic visit should have a careful cardiac examination during the episode (looking for a new S 4 or S 3 , new or worsening MR murmur, rales) and an immediate ECG (looking for transient changes in the ST-segment or T-wave). A therapeutic trial with sublingual NTG can be attempted after these steps if the discomfort is still present. Repeat examination and an ECG should be performed once symptoms are completely resolved. Risk Stratification and Further Management Recommendation: Exercise or pharmacologic stress testing generally should be part of the detailed outpatient workup. However, patients found to have high-risk features (see Table 8), such as evidence of significant LV dysfunction, or an interval acceleration or worsening of symptoms while on appropriate levels of medical therapy, should be considered for direct referral to cardiac catheterization. In addition, patients who have symptoms felt very unlikely to be due to CAD or who are felt to be at very low risk for cardiac events can be managed conservatively, with stress testing reserved for recurrent or worsening symptoms (strength of evidence = C). After detailed clinical assessment, the clinician will have formed an estimate of the likelihood of CAD (see Table 7) and will have made a clinical judgment of the risk of short-term adverse events (see Table 8). Patients found to have high-risk features, especially those with evidence of LV dysfunction or CHF, should be considered for prompt ICU admission for intensive medical care (see Chapter 4). Patients who have a low likelihood of CAD and are at low risk may benefit by further evaluation that may include a trial of nitrates and beta blockers. Use of noninvasive testing in this population should be delayed until the clinical presentation is more clear to avoid the anxiety and cost associated with the false-positive test common in this low-risk population. In general, all intermediate-risk patients and low-risk patients with an intermediate or high likelihood of CAD benefit from noninvasive testing. A more complete discussion of noninvasive testing in this patient group is included in Chapter 6. Outpatient Treatment of Symptoms Recommendation: Patients should be instructed in the proper use of sublingual NTG tablets (strength of evidence = C). Recommendation: Medical therapy for presumed CAD usually begins with sublingual NTG, followed by oral beta blockers. Long-acting topical or oral nitrates may be added, but care should be taken to use regimens that reduce the likelihood of tolerance. In general, for low-risk outpatients, therapy with ASA and one antianginal medication is sufficient initial treatment unless patients have additional indications for multiagent therapy (e.g., hypertension, supraventricular arrhythmia) (strength of evidence = C). Long-acting forms of antianginal drugs are preferable to enhance patient compliance (strength of evidence = C). Recommendation: Patients with established CAD who are already on medical therapy should have their medical regimen reviewed and dosages increased as appropriate and as tolerated (strength of evidence = C). Recommendation: Patients with established CAD or who are judged to be intermediate or high likelihood for CAD should be maintained on ASA at 160 to 324 mg per day unless contraindications are present (strength of evidence = A, evidence cited in Chapter 2). Patients unable to take ASA because of a history of true hypersensitivity or recent significant GI bleeding may be started on ticlopidine 250 mg twice per day as a substitute (strength of evidence = B, evidence cited in Chapter 4). The symptomatic therapy of patients with low-risk unstable angina not requiring hospitalization involves the use of sublingual NTG for treatment of individual anginal episodes and prophylactic therapy with an agent from one of the three major classes of antianginal drugs (nitrates, beta blockers, calcium antagonists). In general, it is reasonable to start therapy with one major antianginal, preferably in a long-acting preparation, and proceed to a second agent only if there are recurrent symptoms on optimal doses of the first agent. In addition, ASA should be a standard part of each regimen. The details of these therapies and the evidence for their use are described in Chapter 4. Recommendation: Patients who continue to report symptoms they consider to reflect cardiac disease and are not reassured that they do not have CAD by appropriate noninvasive tests, counseling, and rehabilitation may be candidates for cardiac catheterization to confirm the absence of CAD (strength of evidence = C). Some patients who present with symptoms suggestive of unstable angina and are initially categorized as having low likelihood of CAD will continue to report symptoms suggestive of angina despite an antianginal regimen that appears appropriate. The medical provider should first review all diagnoses and management decisions and, if appropriate, obtain or repeat other noninvasive exercise or pharmacologic stress tests. Fear of heart disease or other psychological problems commonly underlies complaints of cardiovascular symptoms which are out of proportion to objective evidence of ischemia. Some patients benefit from more complete and frequent counseling and reassurance. This group of patients will often respond to cardiac rehabilitation in a structured environment with supervised exercise. A trial of simple measures is reasonable in this group of patients, but failure to respond may necessitate the decision to perform a cardiac catheterization with the intention of confirming the absence of coronary artery disease. If this is to be undertaken, patients must be informed of the reason for the procedure when they provide informed consent. Some patients find sufficient reassurance with angiographic documentation of normal coronary arteries that their symptoms gradually dissipate. Patients who continue to have symptoms they consider to be angina despite normal coronary angiograms may have small-vessel or vasospastic coronary artery disease requiring further evaluation that is not covered by this guideline. Other patients with continued symptoms but no objective evidence of ischemia or CAD may benefit from evaluation and counseling by medical practitioners other than cardiovascular specialists. Patient Counseling Patients and their families and advocates should understand the most likely diagnosis at the conclusion of the outpatient evaluation. Discussion should deal directly with clinical and test results that predict risk and possible outcomes. Further evaluation and treatment options should be discussed. Patients should receive a clear explanation of the rationale for use of medicines and suggested dosages, as well as possible side effects from the doctor, nurse, or pharmacist. On return visits, patients should be asked about their reaction and compliance as well as perceived effectiveness of the treatment plan outlined on the prior visit. All patients should be counseled on risk-factor modification. Medical Record Information that should be updated or added to the medical record at the conclusion of outpatient management includes: * Age and sex. * Duration and nature of symptoms prior to presentation. * Previous history of CAD; if yes, prior noninvasive test result, cardiac catheterization result, and/or myocardial revascularization procedure (bypass or angioplasty). * Medication and drug use. * Risk factors (diabetes, smoking, hypercholesterolemia, hypertension). * Systemic causes for precipitating or exacerbating ischemia. * ECG interpretation. * Initial and final assignment of likelihood of CAD (high, intermediate, low) and basis. * Initial and final risk assignment (high, intermediate, low) and basis. * Summary of other pertinent positive and negative findings. * Patient counseling, including assessment of patient response. * Disposition for further care. * Results of ancillary clinical studies. * Final diagnosis. * Final disposition. * Effectiveness of antianginal medication used. Duration of Outpatient Phase Typically, the interval between initial presentation and initiation of comprehensive outpatient evaluation should be no more than 72 hours. Generally, one clinic visit should be sufficient to establish a working diagnosis, assess risk, and develop a management plan. Serial outpatient evaluation and noninvasive testing may be required depending on the patient's specific findings and response to treatment. Patients with specific indications may be referred for outpatient or inpatient cardiac catheterization. 8 Guideline: Hospital Discharge and Postdischarge Care Background The natural history of unstable angina is typically characterized by either progression to nonfatal MI or death on the one hand, or resumption of the more quiescent clinical course of chronic stable angina on the other. The acute phase of unstable angina is usually over within 8 weeks. The need for continued hospitalization of the unstable angina patient is determined by whether the inpatient objectives of that hospital admission have been achieved. Patients who have undergone successful revascularization will usually have the remainder of their hospitalization defined by the standard protocol for the given procedure (e.g., 1 to 2 days for PTCA, 5 to 7 days for CABG surgery). Patients electing medical treatment after a cardiac catheterization or functional study include both a low-risk group that can be rapidly discharged (e.g., 1 to 2 days after testing) and a high-risk group unsuitable for or unwilling to have coronary revascularization. These latter patients may require a prolonged hospitalization to ensure adequate (or as adequate as possible) symptom control and that risk of cardiac events in the next 4 to 6 weeks has fallen to an acceptably low level. Management of all these patient groups prior to hospital discharge is described in the preceding chapters. Details and objectives of care from the time of hospital discharge until the final clinic visit for the unstable angina episode are described in this chapter (Figure 13 ). Objectives of Care The goal during the hospital discharge phase is to prepare the patient for normal activities to the extent possible. The goal of postdischarge outpatient care is to make adjustments in the discharge regimen that appear most appropriate after an initial period away from direct patient care. The long-term management of the unstable angina event ends as the patient reenters the stable phase of CAD. Approach to Care Objectives Discharge Medical Regimen Recommendation: Patients should continue on ASA, 80 mg to 324 mg per day, indefinitely after discharge (strength of evidence = B, evidence cited in Chapter 3). Recommendation: In general, those classes of medications necessary to achieve adequate symptom control should be continued after discharge. Patients with successful revascularization without recurrent ischemia do not require postdischarge antianginal therapy. Patients with unsuccessful revascularization or with recurrent symptoms following revascularization should be continued on the regimen required in hospital to control their symptoms (strength of evidence = C). Recommendation: All patients with signs and symptoms suggesting ongoing ischemia should be given sublingual NTG and instructed in its use (strength of evidence = C). Recommendation: Antihypertensive and antihyperlipidemic workups and therapies started prior to admission or initiated in the hospital should be continued in the postdischarge phase (strength of evidence = C). The use of and rationale for different medical agents have been described earlier in this guideline. In most cases, the inpatient medical regimen used in the nonintensive phase will be continued postdischarge. The need for continued medical therapy after discharge relates to potential prognostic benefits (primarily shown for ASA and beta blockers), control of symptoms (nitrates and calcium antagonists), and treatment of major risk factors, such as hypertension, hyperlipidemia, and diabetes mellitus. Thus, selection of a medical regimen will be individualized to the specific needs of each patient and the events that have occurred in hospital. Discharge of a patient from the hospital often requires a team effort from the medical staff (physicians, nurses, dietitians, pharmacists, rehabilitation specialists, physical and occupational therapists). Use of instruction sheets can help to document and reinforce the instructions given but should not be used in lieu of in-person instruction. Postdischarge Followup Recommendation: The plan for followup medical care should be set, whenever possible, at the time of discharge (strength of evidence = C). In general, low-risk patients and patients with successful CABG or PTCA should be seen in an outpatient facility at 2 to 6 weeks, and higher risk patients should return in 1 to 2 weeks (strength of evidence = C). Clinical information available at discharge has been shown by Cox analysis to predict death within 1 year in 515 survivors of hospitalization for non-Q-wave MI, including persistent ST-segment depression, CHF, advanced age, and ST-segment elevation (Schechtman, Capone, Kleiger et al., 1989). Patients with all high-risk markers present had a 14-fold increase in mortality compared with patients with all markers absent. Patients recognized to be at high risk for a cardiac event after discharge deserve earlier and more frequent followup than low-risk patients. Recommendation: Patients with recurrent unstable angina should be managed as specified in an earlier chapter of this guideline corresponding to the clinical situation (strength of evidence = B, evidence cited in Chapter 6). Recommendation: Patients who have stable or no anginal symptoms at this followup visit should be managed further for stable CAD (strength of evidence = C). It is presently unclear whether patients who come through an episode of unstable angina without complications are at increased risk for future episodes of unstable angina, but their overall risk for death or MI is similar to that of other CAD patients with their characteristics who have not had unstable angina. The last element in the management of unstable angina, therefore, is a followup clinic visit at the point when the patient's disease activity has returned to the baseline level. Patient Counseling Use of Medications Recommendation: The patient and his or her family members or advocate should be instructed in the purpose, dose and major side effects of each medicine prescribed using language the patient can understand (strength of evidence = C). Recommendation: Specific instructions for the proper use of sublingual NTG are especially important, since response of chest pain to this specific regimen is useful in assessing the nature of recurrent symptoms (strength of evidence = C). Monitoring Symptoms Recommendation: Because the hospital stay for unstable angina patients is often very short, it has been found that one way to increase patient compliance to the treatment regimen and risk-factor modification program is to provide telephone followup (strength of evidence = B). Either formal or informal telephone followup can serve to reinforce in-hospital learning, provide reassurance, and answer the patient's questions. Beckie (1989) found that bypass patients in a telephone followup program telephoned their physicians less frequently and had fewer readmissions, lower anxiety, and higher CAD knowledge scores compared with the control group. Where personnel and budget resources allow, the health care team may consider establishing such a followup system in which nurses telephone patients approximately once a week for the first 4 weeks after discharge. This structured program would gauge the progress of the patient's recovery, reinforce the CAD education taught in hospital, address patient questions and concerns, and monitor progress in meeting risk behavior modification goals. Recommendation: Recurrent symptoms lasting more than 1 to 2 minutes should prompt the patient to stop his or her activities, sit down, and place an NTG tablet under the tongue. This may be repeated twice at 5-minute intervals for two additional tablets. If symptoms persist after three NTG tablets, the patient should promptly seek medical attention (strength of evidence = C). Recommendation: If symptoms change in pattern (e.g., asymptomatic to symptomatic, more frequent or more severe symptoms), the patient should contact his or her primary care physician and discuss whether changes in the management plan are warranted. However, if the patient cannot reach a physician and chest pain persists for more than 20 minutes or despite three NTG tablets, he or she should seek transportation to the nearest hospital ED either by ambulance or the fastest available alternative (strength of evidence = C). Activity Level and Lifestyle Changes Recommendation: Specific instructions should be given on smoking cessation, daily exercise, and diet (strength of evidence = B). Where possible and appropriate, consideration should be given to referral to a smoking-cessation program or clinic and/or an outpatient cardiac rehabilitation program (strength of evidence = C). The health care team should work with patients and their families to set specific goals for risk-factor reduction. In some cases, the family may be able and willing to support the patient further by also making changes in risk behaviors (e.g., cooking low-fat meals for the entire family, exercising together). Particular attention should be paid to smoking cessation. Daly, Mulcahy, Graham, and colleagues (1983) measured the long-term effects of smoking on patients with unstable angina. For men under 60 years of age, those who continued to smoke had a risk of death from all causes 5.4 times that of men who stopped smoking (p <0.05). More specific recommendations on risk-factor modification and cardiac rehabilitation are beyond the scope of this guideline. Recommendation: Health care providers should initiate a conversation with the patient to discuss the safety and timing of the resumption of sexual activity (e.g. 2 weeks for low-risk patients to 4 weeks for post-CABG surgery patients) (strength of evidence = C). Very often patients will not ask their physicians or other health care providers about resuming sexual activity after their hospitalization. When appropriate, patients need to be reassured that sexual activity is still possible, and it is not likely to result in death or recurrent symptoms. Recommendation: Beyond the instructions for daily exercise, patients require specific instruction on activities that are permissible and those that should be avoided (e.g., heavy lifting, climbing stairs, yard work, household activities). Specific mention should be made of resumption of driving and return to work (strength of evidence = C). Medical Record The patient's medical record from the time of hospital discharge should indicate the discharge medical regimen, the major instructions about postdischarge activities and rehabilitation, and the patient's understanding and plan for adherence to the recommendations. The medical record of the final outpatient visit after full resolution of the episode of unstable angina should summarize cardiac events, current symptoms, medication changes since hospital discharge or last outpatient visit, and document the plan for future care as a patient with stable CAD.