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/update_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)

This is a Guideline Update of the 2000 Unstable Angina Guidelines. To highlight the changes, deleted text is indicated by strikeout, and revised text is presented in brown. A clean version of the document, with changes fully incorporated, is available for download and print.

V. Hospital Discharge and Post-Hospital Discharge Care

The acute phase of UA/NSTEMI is usually over within 2 months. The risk of progression to MI or the development of recurrent MI or death is highest during that period. At 1 to 3 months after the acute phase, most patients resume a clinical course similar to that in patients with chronic stable coronary disease (Figure 3).

The broad goals during the hospital discharge phase, as described in this section, are 2-fold: 1) to prepare the patient for normal activities to the extent possible and 2) to use the acute event as an opportunity to reevaluate long-term care, particularly lifestyle and risk factor modification. Aggressive risk factor modification is the mainstay of the long-term management of stable CAD. Patients who have undergone successful PCI with an uncomplicated course are usually discharged the next day, and patients who undergo uncomplicated CABG are generally discharged 4 to 7 days after CABG. Medical management of low-risk patients after noninvasive stress testing and coronary arteriography can typically be accomplished rapidly with discharge on the day of or the day after testing. Medical management of a high-risk group of patients who are unsuitable for or unwilling to undergo revascularization may require a prolonged hospitalization period to achieve the goals of adequate symptom control and minimization of the risk of subsequent cardiac events.

A. Medical Regimen

In most cases, the inpatient anti-ischemic medical regimen used in the nonintensive phase (other than intravenous NTG) should be continued after discharge and the antiplatelet/anticoagulant medications should be changed to an outpatient regimen. The goals for continued medical therapy after discharge relate to potential prognostic benefits (primarily shown for ASA, beta-blockers, cholesterol-lowering agents, and ACEIs, especially for EF less than 0.40), control of ischemic symptoms (nitrates, beta-blockers, and calcium antagonists), and treatment of major risk factors such as hypertension, smoking, hyperlipidemia, and diabetes mellitus (see later). Thus, the selection of a medical regimen is individualized to the specific needs of each patient based on the in-hospital findings and events, the risk factors for CAD, drug tolerability, or the type of recent procedure. The mnemonic ABCDE (Aspirin and antianginals; Beta-blockers and blood pressure; Cholesterol and cigarettes; Diet and diabetes; Education and exercise) has been found to be useful in guiding treatment ⁽²⁶⁾.

An effort by the entire staff (physicians, nurses, dietitians, pharmacists, rehabilitation specialists, and physical and occupational therapists) is often necessary to prepare the patient for discharge. Both the patient and family should receive instructions about what to do if symptoms occur in the future ^(333a). Direct patient instruction is important and should be reinforced and documented with written instruction sheets. Enrollment in a cardiac rehabilitation program after discharge may enhance patient education and enhance compliance with the medical regimen.

Recommendations

Class I

1. Drugs required in the hospital to control ischemia should be continued after hospital discharge in patients who do not undergo coronary revascularization, patients with unsuccessful revascularization, or patients with recurrent symptoms after revascularization. Upward or downward titration of the doses may be required. (Level of Evidence: C)
2. All patients should be given sublingual or spray NTG and instructed in its use. (Level of Evidence: C)
3. Before discharge, patients should be informed about symptoms of AMI and should be instructed in how to seek help if symptoms occur. (Level of Evidence: C)

1. Long-Term Medical Therapy
Many patients with UA/NSTEMI have chronic stable angina at hospital discharge. The management of the patient with stable CAD is detailed in the ACC/AHA/ACP-ASIM Guidelines for the Management of Patients With Chronic Stable Angina ⁽²⁶⁾. The following are recommendations for pharmacotherapy to prevent death and MI.

Recommendations

Class I

1. Aspirin 75 to 325 mg per d in the absence of contraindications. (Level of Evidence: A)
2. Clopidogrel 75 mg daily (in the absence of contraindications) for patients with a contraindication to ASA. when ASA is not tolerated because of hypersensitivity or gastrointestinal intolerance. (Level of Evidence: AB)
3. The combination of ASA and clopidogrel for 9 months after UA/NSTEMI. (Level of Evidence: B)
4. Beta-blockers in the absence of contraindications. (Level of Evidence: B)
5. Lipid-lowering agents and diet in post-ACS patients, including postrevascularization patients, with low-density lipoprotein (LDL) cholesterol of greater than 130 mg per dL. (Level of Evidence: A)
6. Lipid-lowering agents if LDL cholesterol level after diet is greater than 100 mg per dL. (Level of Evidence: B)
7. ACEIs for patients with CHF, LV dysfunction (EF less than 0.40), hypertension, or diabetes. (Level of Evidence: A)

A reduction in the rates of mortality and vascular events was reported in the Heart Outcomes Prevention Evaluation (HOPE) Study ⁽¹⁶³⁾ with the long-term use of an ACEI in moderate-risk patients with CAD, many of whom had preserved LV function, as well as patients at high risk of developing CAD. Other agents that may be used in patients with chronic CAD are listed in Table 21 and are discussed in detail in the ACC/AHA/ACP-ASIM Guidelines for the Management of Patients With Chronic Stable Angina ⁽²⁶⁾.

Although observational data suggest a protective effect of hormone replacement therapy (HRT) for coronary events, the only randomized trial of HRT for secondary prevention of death and MI that has been completed (Heart and Estrogen/progestin Replacement Study [HERS]) failed to demonstrate a beneficial effect ⁽³³⁴⁾. Disturbingly, there was an excess risk for death and MI early after HRT initiation. It is recommended that postmenopausal women who receive HRT may continue but that HRT should not be initiated for the secondary prevention of coronary events. There may, however, be other indications for HRT in postmenopausal women (e.g., prevention of flushing, osteoporosis).

B. Postdischarge Follow-Up

Recommendations

Class I

1. Discharge instructions should include a follow-up appointment. Low-risk medically treated patients and revascularized patients should return in 2 to 6 weeks, and higher-risk patients should return in 1 to 2 weeks. (Level of Evidence: C)
2. Patients managed initially with a conservative strategy who experience recurrent unstable angina or severe (CCS Class III) chronic stable angina despite medical management who are suitable for revascularization should undergo coronary arteriography. (Level of Evidence: B)
3. Patients who have tolerable stable angina or no anginal symptoms at follow-up visits should be managed with long-term medical therapy for stable CAD. (Level of Evidence: B)

The risk of death within 1 year can be predicted on the basis of clinical information and the ECG. For 515 survivors of hospitalization for NSTEMI, risk factors include persistent ST-segment depression, CHF, advanced age, and ST-segment elevation at discharge ⁽³³⁵⁾. Patients with all high-risk markers present had a 14-fold greater mortality rate than did patients with all markers absent. Elevated cardiac TnT levels have also been demonstrated to provide independent prognostic information for cardiac events at 1 to 2 years. For patients with all ACS in a GUSTO-IIa substudy, age, ST-segment elevation on admission, prior CABG, TnT, renal insufficiency, and severe COPD were independently associated with risk of death at 1 year ^(100,336). For UA/NSTEMI patients, prior MI, TnT positivity, accelerated angina before admission, and recurrent pain or ECG changes were independently associated with risk of death at 2 years. Patients managed with an initial conservative strategy (see Section III) should be reassessed at the time of return visits for the need for cardiac catheterization and revascularization. Specifically, the presence and severity of angina should be ascertained. Rates of revascularization during the first year have been reported to be high ⁽³³⁷⁾. Long-term (7 years) follow-up of 282 patients with UA demonstrated high event rates during the first year (MI 11%, death 6%, PTCA 30%, CABG 27%). However, after the first year, event rates were low ⁽³³⁷⁾. Independent risk factors for death/MI were age greater than 70 years, diabetes, and male sex. Mental depression has also been reported to be an independent risk factor for cardiac events after MI and occurs in up to 25% of such patients ⁽³³⁸⁾. Patients recognized to be at high risk for a cardiac event after discharge deserve earlier and more frequent follow-up than low-risk patients.

The overall long-term risk for death or MI 2 months after an episode of UA/NSTEMI is similar to that of other CAD patients with similar characteristics. van Domburg et al. ⁽³³⁷⁾ reported low rates of admission for recurrent chest pain (5%, 4%, 3%, and 2% at 1, 3, 5, and 7 years, respectively). When the patient has returned to the baseline level, typically 6 to 8 weeks after hospitalization, arrangements should be made for long-term regular follow-up visits, as for stable CAD. Cardiac catheterization with coronary angiography is recommended for any of the following situations: 1) significant increase in anginal symptoms, including recurrent UA; 2) high-risk pattern (e.g., greater than or equal to 2-mm ST-segment depression, systolic blood pressure decline of greater than or equal to 10 mm Hg) on exercise test; 3) CHF; 4) angina with mild exertion (inability to complete Stage 2 of the Bruce protocol for angina); and 5) survivors of sudden cardiac death. Revascularization is recommended based on the coronary anatomy and ventricular function (see Section IV and ACC/AHA/ACP-ASIM Guidelines for the Management of Patients With Chronic Stable Angina ^[26]).

C. Use of Medications

Recommendations

Class I

1. Before hospital discharge, patients and/or designated responsible caregivers should be provided with well-understood instructions with respect to medication type, purpose, dose, frequency, and pertinent side effects. (Level of Evidence: C)
2. Anginal discomfort lasting greater than 2 or 3 min should prompt the patient to discontinue the activity or remove himself or herself from the stressful event. If pain does not subside immediately, the patient should be instructed to take NTG. If the first tablet or spray does not provide relief within 5 min, then a second and third dose, at 5-min intervals, should be taken. Pain that lasts greater than 15 to 20 min or persistent pain despite 3 NTG doses should prompt the patient to seek immediate medical attention by calling 9-1-1 and going to the nearest hospital ED, preferably via ambulance or the quickest available alternative. (Level of Evidence: C)
3. If the pattern of anginal symptoms change (e.g., pain is more frequent or severe or is precipitated by less effort or now occurs at rest), the patient should contact his or her physician to determine the need for additional treatment or testing. (Level of Evidence: C)

Either formal or informal telephone follow-up can serve to reinforce in-hospital instruction, provide reassurance, and answer the patient's questions ⁽³³⁹⁾. If personnel and budget resources are available, the healthcare team may consider establishing a follow-up system in which nurses call patients on the telephone approximately once a week for the first 4 weeks after discharge. This structured program can gauge the progress of the patient's recovery, reinforce the CAD education taught in the hospital, address patient questions and concerns, and monitor progress in meeting risk factor modification goals.

D. Risk Factor Modification

Recommendations

Class I

1. Specific instructions should be given on the following:
   1. Smoking cessation and achievement or maintenance of optimal weight, daily exercise, and diet. (Level of Evidence: B)
   2. HMG-CoA reductase inhibitors for LDL cholesterol greater than 130 mg per dL. (Level of Evidence: A)
   3. Lipid-lowering agent if LDL cholesterol after diet is greater than 100 mg per dL. (Level of Evidence: B)
   4. A fibrate or niacin if high-density lipoprotein (HDL) cholesterol is less than 40 mg per dL, occurring as an isolated finding or in combination with other lipid abnormalities. (Level of Evidence: B)
   5. Hypertension control to a blood pressure of less than 130 per 85 mm Hg. (Level of Evidence: A)
   6. Tight control of hyperglycemia in diabetes. (Level of Evidence: B)
2. Consider the referral of patients who are smokers to a smoking cessation program or clinic and/or an outpatient cardiac rehabilitation program. (Level of Evidence: B)

Class IIa

1. HMG-CoA reductase inhibitors and diet for LDL cholesterol greater than 100 mg per dL begun 24 to 96 h after admission and continued at hospital discharge. (Level of Evidence: B)
2. Gemfibrozil or niacin for patients with HDL cholesterol of less than 40 mg per dL and triglycerides of greater than 200 mg per dL. (Level of Evidence: B)

The healthcare team should work with patients and their families to educate them regarding specific targets for LDL cholesterol, blood pressure, weight, and exercise. The family may be able to further support the patient by making changes in risk behavior (e.g., cooking low-fat meals for the entire family, exercising together). This is particularly important when a screening of the family members reveals common risk factors, such as hyperlipidemia, hypertension, and obesity.

There is a wealth of evidence that cholesterol-lowering therapy for patients with CAD and hypercholesterolemia ⁽³⁴⁰⁾ and for patients with mild cholesterol elevation (mean 209 to 218 mg per dL) after MI and UA reduces vascular events and death ^(341,342). Patients should be educated regarding cholesterol reduction and their current and target cholesterol levels. Patients who have undergone PTCA or CABG derive benefit from cholesterol lowering ⁽³⁴³⁾ and deserve special counseling lest they mistakenly believe that revascularization obviates the need for change. The National Cholesterol Education Program 2 recommends a target LDL cholesterol level less than 100 mg per dL, a low-saturated-fat diet for persons with an LDL cholesterol level greater than 100 mg per dL, and the addition of medication for persons with an LDL cholesterol level greater than 130 mg per dL ^(343a,343b). The treatment of hypertriglyceridemia and low HDL cholesterol (less than 35 mg per dL) with gemfibrozil has resulted in reduced cardiovascular events in men with coronary heart disease ⁽²¹⁷⁾. Either niacin or gemfibrozil may be added to the diet when fasting triglycerides are greater than 200 mg per dL ⁽⁵⁾.

The National Cholesterol Education Program III has raised the target for HDL cholesterol to 40 mg per dL ⁽⁵⁴⁵⁾. In the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study, 3,086 patients were randomized to treatment with an aggressive lipid-lowering regimen of atorvastatin 80 mg per d or placebo 24 to 96 h after an ACS ⁽⁵⁴⁶⁾. At 16 weeks of follow-up, the primary end point of death, nonfatal MI, resuscitated cardiac arrest, or recurrent severe myocardial ischemia was reduced from 17.4% in the placebo group to 14.8% in the atorvastatin group (p = 0.048). There were no significant differences in the risk of death, nonfatal MI, cardiac arrest, or worsening heart failure in the 2 groups, but there were fewer strokes and a lower risk of severe recurrent ischemia. The Lipid-Coronary Artery Disease (L-CAD) study was a small trial that randomized 126 patients with an ACS to early treatment with pravastatin, alone or in combination with cholestyramine or niacin, or to usual care. At 24 months, the patients who received early aggressive treatment had a lower incidence of clinical events (23%) than the usual-care group (52%; p = 0.005) ⁽⁵⁴⁷⁾.

Although the evidence from clinical trials that predischarge initiation of lipid-lowering therapy [the MIRACL ⁽⁵⁴⁶⁾ and L-CAD studies ⁽⁵⁴⁷⁾] is not yet robust or definitive, observational studies support this policy. In the Swedish Registry of Cardiac Intensive Care of almost 20,000 patients, the adjusted relative risk of mortality was 25% lower in patients in whom statin therapy was initiated before hospital discharge ⁽⁵⁴⁸⁾.

Patients in whom lipid-lowering therapy was begun in the hospital were much more likely to be on such therapy at a later time. In one demonstration project, the Cardiovascular Hospitalization Atherosclerosis Management Program (CHAMP), the inhospital initiation of lipid-lowering therapy increased the percentage of patients treated with statins 1 year later from 10% to 91% and of those with an LDL cholesterol less than 100 mg per dL from 6% to 58% ⁽⁵⁴⁹⁾.

Although additional trials are ongoing, there appear to be no adverse effects and substantial advantages to the initiation of lipid-lowering therapy before hospital discharge ^(550,551). Such early initiation of therapy has also been recommended in the third report of the National Cholesterol Education Program (NCEP) ⁽⁵⁴⁵⁾.

Despite the overwhelming evidence for the benefits of statin therapy in patients with elevated LDL cholesterol levels, almost no data exist about the timing of the initiation of therapy in ACS. Fewer than 300 patients have been entered into the currently completed trials within 4 months of ACS. These trials excluded ACS patients in the acute phase because of several concerns. In the acute setting, the LDL cholesterol level drops, so the implications of further acute depression of levels are unclear. A theoretical argument can be made that the inhibition of vascular smooth muscle cell proliferation with statins could prevent plaque stabilization, and the beneficial effects of statin therapy have not been observed in the first several months of therapy in long-term trials. These theoretical concerns must be weighed against substantial evidence that if lipid-lowering therapy is not instituted in the acute setting, it often is forgotten. Another potential benefit of early treatment with statins is the rapid improvement in endothelial function they induce. Before pharmacological LDL-lowering therapy is begun, a baseline of 2 or 3 fasting lipoprotein measurements should be obtained; metabolic stability should be attained before such therapy is begun (343c).

Blood pressure control is an important goal, and hypertensive patients should be educated regarding this goal ⁽³⁴⁴⁾. Systolic and diastolic blood pressures should be in the normal range (systolic less than 135 mm Hg, diastolic less than 85 mm Hg). Particular attention should be paid to smoking cessation. Daly et al. ⁽³⁴⁵⁾ quantified the long-term effects of smoking on patients with ACS. Men less than 60 years old who continued to smoke had a risk of death from all causes 5.4 times that of men who stopped smoking (p less than 0.05). Referral to a smoking cessation program and the use of nicotine patches or gum are recommended ⁽³⁴⁶⁾. Bupropion, an anxiolytic agent and weak inhibitor of neuronal uptake of neurotransmitters, has been effective when added to brief regular counseling sessions in helping patients to quit smoking. The treatment of 615 study subjects for 7 weeks resulted in smoking cessation rates of 28.8% for the 100 mg per d dosage and 44.2% for 300 mg per d dosage compared with 19.6% for placebo-assigned patients (p less than 0.001) The abstinence rate at 1 year was 23.0% for those treated with 300 mg per d bupropion vs. 12.4% for those receiving placebo ⁽³⁴⁶⁾. Family members who live in the same household should also be encouraged to quit smoking to help reinforce the patient's effort and to decrease the risk of second-hand smoke for everyone.

Tight glucose control in diabetics during and after MI (DIGAMI study) has been shown to lower acute and 1-year mortality rates in ACS ⁽³⁴⁷⁾. Tight glucose control (HbA1c less than 7.0%) reduces microvascular disease ^(348,349) and is strongly recommended. The recently published UK Prospective Diabetes Study (UKPDS) ^(349-351) demonstrated that the control of glycemia reduced diabetes-related events, including MI (16% reduction, p = 0.052), for newly detected type 2 diabetics aged 25 to 65 years without symptomatic macrovascular disease.

Overweight patients should be instructed in a weight loss regimen, with emphasis on the importance of regular exercise and a life-long prudent diet to maintain ideal weight.

Although there is an association of elevated homocysteine blood levels and CAD, a reduction in homocysteine levels with folate has not yet been demonstrated to reduce the risk of CAD events ^(352,353).

Very often, patients will not ask their physicians or other healthcare providers about the resumption of sexual activity after hospital discharge. When appropriate, patients need to be reassured that sexual activity is still possible. The resumption of sexual activity can typically occur within 7 to 10 days in stable patients. Nitrates and sildenafil should not be used together within 24 h of each other.

Recommendation

Class I

Beyond the instructions for daily exercise, patients require specific instruction on activities (e.g., heavy lifting, climbing stairs, yard work, household activities) that are permissible and those that should be avoided. Specific mention should be made regarding resumption of driving and return to work. (Level of Evidence: C)

Daily walking can be encouraged immediately after discharge. Driving regulations vary among states. Typically, patients may begin driving 1 week after discharge, but they must comply with all state department of motor vehicle restrictions, which may include the need to be accompanied and to avoid stressful circumstances such as rush hours, inclement weather, night driving, heavy traffic, and high speeds. Commercial air travel may be undertaken by stable patients (without fear of flying) within the first 2 weeks of discharge if they travel with a companion, carry sublingual NTG, and request airport transportation to avoid rushing.

E. 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. After resolution of the acute phase of UA/NSTEMI, the medical record should summarize cardiac events, current symptoms, and medication changes since hospital discharge or the last outpatient visit and should document the plan for future care.