Unstable Angina Treatment & Management

Patients with unstable angina require admission to the hospital for bed rest with continuous telemetry monitoring. Intravenous access should be obtained and supplemental oxygen started. Because the course of unstable angina is highly variable and potentially life threatening, the aggressiveness of approach needs to be established expeditiously.

The key in this decision-making is to select the initial management approach: invasive or conservative strategy. Algorithms are in the charts below.

An invasive strategy refers to the routine use of cardiac catheterization with possible revascularization, and a conservative strategy refers to initial medical management with the possible use of cardiac catheterization if indicated by failure of medical therapy or objective evidence of ischemia (dynamic electrocardiographic changes or abnormal noninvasive stress test results). Determination of the preferred strategy depends on the patient's clinical characteristics and clinical risk (see Table 5 below).

Specific therapy for primary causes of ischemia should be directed at each pathophysiologic origin of unstable angina: increased myocardial rate-pressure product, coronary vasoconstriction, platelet aggregation, and thrombosis.

Several guidelines and decision algorithms are available and are especially helpful in identifying patients at low risk in whom hospital admission can be avoided.

The level of care and expertise of the different units vary from hospital to hospital. For example, the intermediate care unit in certain tertiary cardiac centers may be equipped and appropriately staffed for treatment of asymptomatic patients, but high-risk patients with unstable angina would be more appropriately cared for in an ICU in a community hospital setting.

Indications for intensive care

Intensive care unit and/or emergency revascularization disposition is indicated by the following:

• TIMI Risk Score of 3-7
• New ECG changes in 2 or more leads
• ST elevation greater than 1 mm or Q waves 0.04 seconds or longer
• ST depression greater than 1 mm or T-wave inversion in the context of angina
• New left bundle branch block
• Signs and symptoms of incipient or florid heart failure
• Syncope or sudden death presentation
• Serious new arrhythmias, including second-degree or complete heart block and ventricular tachyarrhythmias
• Refractory angina
• Hypoxia
• Positive cardiac enzyme (CK or troponin)
• Myocardial infarction or coronary stenting within the last 2 weeks

Indications for immediate care

In intermediate care units, patients are admitted when asymptomatic but have any of the following conditions:

• Atrial arrhythmia, supraventricular tachycardia, or low-grade, second-degree atrioventricular block [second-degree atrioventricular block]
• Isolated basilar rales
• Borderline blood pressure
• Symptoms with minimal activity
• Presence of major comorbidity (eg, severe pulmonary, renal, or hepatic disease; bleeding history or dyscrasia)
• Very elderly or frail

Indications for observation

Patients who are otherwise healthy individuals without ischemic ECG changes but with either of the following should be admitted to observation units:

• New-onset symptoms at moderate levels of exertion
• Known coronary artery disease with a presentation that does not suggest true worsening but for which further observation is thought to be prudent

Medical management of adverse events

Medications that provide symptomatic relief but have not been found to have an effect on long-term major events include nitrates, diltiazem or verapamil, other medications used to treat unstable angina, and heparin. Medications that have compelling evidence for reducing short- or long-term adverse events are as follows:

• Aspirin
• Beta-adrenergic blocking agents
• Lipid-lowering agents (statins)
• Angiotensin-converting enzyme (ACE) inhibitors
• Clopidogrel
• Glycoprotein IIb/IIIa antagonists

Medications used in the initial management of unstable angina include the following:

• Aspirin
• Beta-adrenergic blocking agents
• Thienopyridines such as clopidogrel, plasugrel
• Glycoprotein IIb/IIIa antagonists
• Heparin
• Direct thrombin inhibitors
• Nitrates

Aspirin

Administer chewable aspirin 162-325 mg promptly to patients who are not at high risk for bleeding, who do not have ongoing bleeding, or who do not have true intolerance or allergy. Timeliness of administration is essential because platelet aggregation is central to acute coronary syndrome; the peak effect of aspirin can be observed within as short a time as 30 minutes.

Pooled data from more than 2,000 patients revealed a reduction of death or myocardial infarction from 11.8% to 6% with aspirin in cases of unstable angina.

Several studies have shown approximately 40-50% risk reductions for death or myocardial infarction with aspirin at 30-day follow-up and at up to 1-year follow-up in this patient population.

In the event of PCI, aspirin 162-325 mg should be given for at least 1 month after bare metal stent implantation, 3 months after sirolimus-eluting stent implantation, or 6 months after paclitaxel-eluting stent implantation. Thereafter, aspirin 75-162 mg should be continued indefinitely.

Beta-blockers

Clinical trials of beta-blockers in cases of unstable angina have shown decreases in ischemic symptoms and in the occurrence of myocardial infarctions. These benefits have to be counterbalanced by the potential complications of heart failure or cardiogenic shock that have been demonstrated when beta-blockers are used in hemodynamically compromised patients.

Oral beta-blockers (eg, metoprolol) are preferred over intravenous therapy. Studies have associated intravenous beta-blocker therapy with an increased risk of cardiogenic shock in patients presenting with heart failure or high-risk features.

Intravenous beta-blockers may still be indicated in select patients with tachycardia or hypertension and ongoing chest pain.

In vitro studies have shown inhibition of platelet aggregation with beta-blockers.

Thienopyridines

Clopidogrel was the only US Food and Drug Administration (FDA) approved thienopyridine antiplatelet agent when the ACC/AHA 2007 guidelines for the management of patients with unstable angina/non ST-elevation myocardial infarction (UA/NSTEMI) were released. Since then, the FDA has approved a second thienopyridine, prasugrel. The 2011 ACC Foundation (ACCF)/AHA focused update of the 2007 guidelines includes recommendations for the use of prasugrel as well as clopidogrel.^[12]

The 2011 ACCF/AHA update to the guidelines recommends a loading dose of a thienopyridine for patients with UA/NSTEMI for whom PCI is planned. For patients with UA/NSTEMI who are undergoing PCI, a maintenance dose of a thienopyridine should be given for at least 12 months. Early discontinuation should be considered if the risk of bleeding outweighs the expected benefits of thienopyridine therapy. Dosage and timing for each thienopyridine are specified in the Class I recommendations.^[12]

Clopidogrel

Clopidogrel is recommended as the antiplatelet of choice in patients who are intolerant to aspirin, and it is also used as an adjunctive antiplatelet agent in addition to aspirin (dual antiplatelet therapy).^[13]

The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial showed that the addition of clopidogrel to aspirin therapy reduced the incidence of cardiovascular death, myocardial infarction, or stroke from 11.4% to 9.3% (at 1 y), with early benefit shown at 24 hours. However, the results from the clopidogrel/aspirin treatment came at the cost of increased major bleeding in comparison with that occurring in patients on aspirin therapy plus placebo (3.7% vs 2.7%, respectively).^[14]

The PCI-CURE and the Clopidogrel for the Reduction of Events During Observation (CREDO) trials showed significant benefit in the administration of clopidogrel to patients with unstable angina who undergo coronary intervention; pretreatment with clopidogrel 6 hours before intervention was associated with improved outcomes. A loading dose of 600 mg may offer more effective platelet inhibition than 300 mg; increasing the loading dose beyond 600 mg has not shown benefit.

Patients who later undergo CABG (eg, those with multivessel disease) while receiving clopidogrel have an increased risk of major bleeding and a greater frequency of surgery for bleeding. Clopidogrel is recommended to be withheld for at least 5 days prior to elective coronary artery bypass graft because of this increased risk of bleeding. Thus, many physicians choose to hold clopidogrel until the patient's coronary anatomy is defined during coronary angiography.

Even with the above discussion in mind, patients who are clinically unstable should receive clopidogrel or be taken immediately for coronary angiography.

Prasugrel

The 2011 ACCF/AHA focused update to the guidelines for UA/NSTEMI recommends prasugrel as an alternative thienopyridine to clopidogrel. Head-to-head comparison has shown that prasugrel is more effective at reducing clinical events than clopidogrel but the risk of bleeding was increased. Prasugrel is stated to be potentially harmful as part of a dual-platelet regimen in patients with a stroke history for whom PCI is planned. It should only be used sparingly in those 75 years or older, unless the risk of recurrent cardiac ischemia outweighs the elevated bleeding risk.^[12]

Glycoprotein IIb/IIIa antagonists

As previously mentioned, the inflection point for myocardial infarction or death starts at a TIMI Risk Score of 3. Therefore, patients with a score of 3-7 should be considered for use of intravenous glycoprotein IIb/IIIa agents, heparin (low molecular weight or unfractionated), and early cardiac catheterization.

Tens of thousands of patients have been enrolled in randomized clinical trials evaluating glycoprotein IIb/IIIa antagonists in acute coronary syndrome. These trials have shown 30-day relative risk reductions of 22-56% in composite end points, with beneficial trends in each of the component outcomes, largely in association with PCI.

In patients who are undergoing PCI (ie, those with high-risk characteristics), therapy should be started with a small-molecule intravenous glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitor for medical stabilization.

If the patient can be catheterized within the first few hours of presentation and is pain free, an acceptable alternative is to simply commence glycoprotein IIb/IIIa inhibitor in the catheterization laboratory in conjunction with percutaneous revascularization.

All of the currently available glycoprotein IIb/IIIa inhibitors, namely abciximab, eptifibatide, and tirofiban, have been shown to increase the safety of acute PCI, with relative risk reductions in adverse events (including 30-d mortality and infarction) of approximately 30-50%.

The GUSTO-4 randomized clinical trial did not show any benefit for abciximab in medically treated patients who do not undergo PCI. In fact, longer duration of abciximab use was associated with a negative trend in event rates. On the other hand, in the context of PCI, it has been shown to be superior to tirofiban.

Kastrati et al compared the combination of glycoprotein IIb/IIIa inhibitors and heparin with bivalirudin, specifically among patients with NSTEMI undergoing PCI. In a double-blind manner, 1721 patients with acute NSTEMI were randomly assigned to receive abciximab plus unfractionated heparin (861 patients) or bivalirudin (860 patients). The study concluded that abciximab and unfractionated heparin, compared with bivalirudin, failed to reduce death, large recurrent myocardial infarction, urgent target-vessel revascularization, or major bleeding within 30 days. It also increased the risk of bleeding among patients with NSTEMI who were undergoing PCI.^[15]

Of the currently used GP IIb/IIIa inhibitors, only eptifibatide and tirofiban have been shown to be of benefit in high-risk patients treated with medical management alone. The relative reduction in adverse events observed in this setting is on the order of 5-7%. In addition, a meta-analysis of 6 randomized trials (with 31,400 patients) failed to show a mortality benefit in patients who did not undergo PCI. Judgment is required as to whether this small benefit offsets the risk of bleeding events.

Dual and Triple Antiplatelet Therapies

The ACCF/AHA 2011 update to the UA/NSTEMI guideline recommends dual-antiplatelet therapy (aspirin and a second antiplatelet agent) for medium-risk to high-risk patients with definite UA/NSTEMI for whom an initial invasive strategy is chosen. Before PCI, the second antiplatelet agent may be clopidogrel or an IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban preferred). At the time of PCI, the second antiplatelet agent may be clopidogrel, prasugrel, or an IV GP IIb/IIIa inhibitor.^[12]

Precatheterization triple-antiplatelet therapy (aspirin, a thienopyridine, and a GP IIb/IIIa inhibitor) is associated with increased bleeding risk and is recommended only for patients at high risk for ischemic events whose risk of bleeding is not elevated.^[12]

Heparin

The use of low–molecular-weight heparin (LMWH) and the use of intravenous unfractionated heparin (UH) are 2 comparable anticoagulation strategies in the treatment of unstable angina. The many potential benefits of using LMWH include lower rates of bleeding, cost savings, and reduced incidence of heparin-induced thrombocytopenia. However, many interventional cardiologists are uncomfortable using LMWH, because anticoagulation activity cannot be measured during PCI.

Investigators in the Efficacy and Safety of Subcutaneous Enoxaparin in Non–Q-wave Coronary Events (ESSENCE) study compared LMWH (enoxaparin) with unfractionated heparin. The revascularization rate in this study was intermediate at about 30%. The 30-day composite rates of death, myocardial infarction, or recurrent angina were significantly reduced for subjects taking LMWH (19.8% vs 23.3%). However, excess minor bleeding occurred in 11.9% of patients in the LMWH group, versus 7.2% of patients in the non-LMWH group, an important proportion of which were due only to injection site ecchymosis.

Enoxaparin was associated with more major bleeding episodes than was unfractionated heparin (9.1% vs 7.6%, respectively) in the Superior Yield of the New strategy of Enoxaparin Revascularization and Glycoprotein IIb/IIIa Inhibitors (SYNERGY) trial. In the study, high-risk patients with NSTEMI (including those with unstable angina) were randomized into groups that received either unfractionated heparin or enoxaparin. All enrolled patients were treated with an early invasive strategy. No difference in composite end point (death or myocardial infarction by 30 d) was detected. Although more major bleeding episodes occurred in the enoxaparin group, much of this effect was attributed to patients who crossed over to unfractionated heparin after receiving an initial dose of enoxaparin.

Compared with enoxaparin, fondaparinux was associated with a low, but increased, rate of guiding catheter thrombus in the Organization to Assess Strategies for Ischemic Syndromes-5 (OASIS-5) trial. The study compared fondaparinux and enoxaparin in the treatment of unstable angina and NSTEMI. The rate of major bleeding was lower in the fondaparinux group than in the enoxaparin group at 9 days, and fondaparinux treatment was associated with significant reductions in myocardial infarction, stroke, and mortality at 180 days. However, because of the increased rate of guiding catheter thrombus in the fondaparinux group, it is not recommended if urgent PCI is foreseen.

Enoxaparin, fondaparinux, and unfractionated heparin are safe alternative agents used in the treatment of unstable angina. Switching agents (ie, from LMWH to UH) has been associated with excess bleeding and reduced clinical benefit. In patients with an intended conservative strategy, treatment with LMWH may be preferred.

Reactivation of unstable angina after discontinuation of heparin has been documented among subjects not receiving concomitant aspirin therapy.^[16]

Direct thrombin inhibitors

Direct thrombin inhibitors, such as hirudin, lepirudin (recombinant hirudin), and bivalirudin, are potential alternatives to heparin. These agents are much more costly than conventional anticoagulation agents and may be associated with higher rates of bleeding.

In a large meta-analysis comparing direct thrombin inhibitors and heparin in the treatment of patients with acute coronary syndrome, there was a slightly greater reduction in myocardial infarction in the inhibitors group than in the heparin patients (2.8% vs 3.5%, respectively). Treatment with hirudin was associated with an increased risk of major bleeding compared with heparin, whereas treatment with bivalirudin was associated with a lower risk of major bleeding.

GUSTO IIB investigators compared recombinant hirudin with heparin in 12,142 patients, a third of who had STEMI. The hirudin group had a 9% relative risk reduction in 30-day death or myocardial infarction rates (8.9% vs 9.8%), but more moderate bleeding events occurred (8.8% vs 7.7%).^[7]

OASIS-2 was an international clinical trial that involved 10,141 patients. Patients were randomized between heparin (aPTT maintained between 60 and 100 seconds) and lepirudin (0.4 mg/kg bolus followed by 0.15 mg/kg/h 72-h IV infusion). Unlike for GP IIb/IIIa antagonists, no evidence indicates attenuation of myocardial necrosis (based on CK or troponin measurements). Lepirudin has been approved by the FDA for use in patients with heparin-induced thrombocytopenia and associated thrombotic disease. The goal is 1.5-2.5 times the control aPTT values. The dose needs to be adjusted for patients with renal impairment.

The benefits of bivalirudin in patients who undergo coronary stent implantation has been demonstrated in the Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events-2 (REPLACE-2) and Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trials. At present, however, there are insufficient data to support a recommendation of routine bivalirudin use in patients with unstable angina.

Although direct thrombin inhibitors should not be routinely used in the treatment of unstable angina, they may be of clinical benefit in special circumstances, such as heparin-induced thrombocytopenia.

Nitrates

Intravenous nitrate agents may be used in the treatment of ischemic chest pain, symptoms of heart failure, or hypertension but are not associated with appreciable long-term clinical benefit.

These agents are contraindicated for patients with right ventricular infarction, hypertrophic cardiomyopathy, and severe aortic stenosis.

Additional management of unstable angina includes the use of statins (lipid-lowering agents) and ACE inhibitors.

HMG coenzyme A reductase inhibitors (statins)

Multiple large, randomized, secondary prevention trials, including the Heart Protection Study, have demonstrated significant mortality benefit from statin therapy.

Results from the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study and with the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE-IT) TIMI trials suggested that early initiation of antilipidemic agents (statins) in patients with acute coronary syndrome can decrease adverse events within a relatively short term.^{[17, 18]}

The MIRACL clinical trial randomized 3,086 patients with unstable angina to high-dose atorvastatin versus placebo. Therapy resulted in a reduction in the primary end point (ie, death, myocardial infarction, resuscitated cardiac arrest, severe recurrent symptomatic ischemia) from 17.4% to 14.8% within the relatively short period of 4 months. The benefit was mostly for recurrent symptomatic ischemia with objective evidence and requiring emergency rehospitalization (8.4% down to 6.2%).^[17]

The PROVE-IT TIMI 22 trial demonstrated a benefit from statin therapy even in patients with acute coronary syndrome presenting with relatively low serum LDL-C levels (LDL-C < 100 mg/dL, suggesting that the target LDL-C level should be less than 80 mg/dL in these patients.^[18]

Statin therapy should be initiated before hospital discharge to improve patient adherence. Additional clinical benefit may be gained by starting therapy within 24-96 hours of admission.

Angiotensin-converting enzyme inhibitors

ACE inhibitors are of particular benefit in patients with large anterior infarctions, especially with compromised left ventricular function (eg, from STEMI) but without hypotension. The benefit in patients with unstable angina is less clear.

Currently, ACE inhibitors are recommended in patients with left ventricular dysfunction or congestive heart failure, diabetes, and hypertension.

ACE inhibitor therapy may be started within 24 hours of admission and titrated for blood pressure effect.

Other medications

Calcium-channel antagonists, antibiotics against Chlamydia pneumoniae, and fibrinolytic agents currently have no established role in the setting of unstable angina.

Most of the clinical trials of fibrinolytic therapy have shown a tendency toward more nonfatal infarctions attributed to procoagulant effects in the context of a nonocclusive thrombus.

Although the available data suggest that the efficacy of ticlopidine is similar to that of aspirin, the use of ticlopidine in the United States was drastically reduced after reports appeared of associated fatal thrombotic thrombocytopenic purpura.

Patients with unstable angina and the following clinical characteristics should be referred for immediate cardiac catheterization:

• Cardiogenic shock
• Severe left ventricular dysfunction
• Angina refractory to medical therapy
• Acute mitral regurgitation
• New ventricular septal defect
• Unstable tachyarrhythmias

Invasive versus conservative therapy

It has been questioned whether patients with unstable angina, but without the clinical characteristics listed above, receive greater benefit from an invasive strategy than from conservative management.

Among patients presenting with unstable angina, approximately 15% have 1-vessel coronary artery disease, 35% have 2-vessel coronary artery disease, and 50% have 3-vessel coronary artery disease. The incidence of left main disease is roughly 5-10%. The rate of thrombus detected at coronary angiography ranges widely from less than 10% among those with chest pain in the previous month to more than 50% among those with rest angina in the preceding 24 hours. This high prevalence of significant disease has led some to advocate routine angiography, whereas the imperfect ability to predict who will develop long-term adverse events has encouraged a tendency toward permissive revascularization.

Older clinical trials, such as TIMI III-B, the Veterans Affairs Non–Q-wave Infarction Strategies In-Hospital (VANQWISH) study, and the Medicine Versus Angiography in Thrombolytic Exclusion (MATE) trial, did not show that routine catheterization was superior to the conservative approach of performing catheterization only in patients with recurrent ischemic symptoms or a significantly positive stress test result. Heightened rates of abrupt vessel closure, stent thrombosis, and myocardial infarction were early hazards observed with angioplasty performed in the acute setting of myocardial ischemia.^{[19, 20]}

The introduction of platelet GP IIb/IIIa inhibitors has neutralized most of the above-mentioned periprocedural complications, so that an early benefit is now observed with contemporary PCI.

The TACTICS/TIMI-18 study showed a very low 30-day and 6-month composite end point of death, myocardial infarction, or rehospitalization for the early invasive strategy. The study entailed the administration of intravenous GP IIb/IIIa (tirofiban), coupled with angiography within 48 hours. The benefit of early invasive strategy was more substantial in intermediate- and high-risk patients (ie, those with TIMI score 3).

The Fragmin During Instability in Coronary Artery Disease II (FRISC-II) trial showed a significant reduction in death or myocardial infarction at 6 months in patients with unstable angina who underwent early catheterization and revascularization, compared with patients who were treated with a noninvasive strategy. This treatment difference was primarily driven by a lower rate of myocardial infarction in the invasive arm than in the noninvasive patient group (7.8% vs 10.1%, respectively). Patients in the invasive arm also had a significant reduction in angina and hospital readmission rates. The treatment benefits were more pronounced in patients with ST-segment depression and cardiac marker elevation.^[21]

Investigators in the RITA 3 study also reported a benefit with the invasive strategy over conservative management in intermediate- to high-risk patients with NSTEMI and ischemic changes on ECG or elevated troponin levels. The combined end point of death, myocardial infarction, and refractory angina at 4 months was significantly reduced in the invasive arm (9.6%) versus the conservative arm (7.6%). While the 2 groups showed no difference in the combined end point (death or nonfatal myocardial infarction) at 1 year, a 5-year follow-up analysis revealed that the invasive strategy was associated with significant reductions in death or nonfatal myocardial infarction.

In contrast to these trials, the Invasive vs Conservative Treatment in Unstable Coronary Syndromes (ICTUS) trial showed no advantage to the use of an early invasive strategy over a selective invasive 1 in 1200 patients with chest pain and elevated troponin who had either a history of coronary artery disease or the presence of ischemic ECG changes. However, the selective invasive group had a 40% rate of revascularization during initial hospital stay.

Timing of catheterization

With regard to the timing of catheterization, the Intracoronary Stenting Angiographic Results Cooling-Off (ISAR-COOL) trial suggested that earlier catheterization provides a significant benefit over later use of the procedure. Patients with NSTEMI who underwent coronary angiography within 6 hours had a lower rate of death or large myocardial infarction at 30 days than did patients who underwent the treatment at 3-5 days (5.9% vs 11.6%, respectively).

Two meta-analyses (one of which included the ICTUS trial) also supported the use of an early invasive strategy in the management of patients with NSTEMI with the most prominent benefit occurring in those patients with high-risk features.

Based on the weight of the current evidence, early invasive strategy benefits high-risk patients with acute coronary syndrome. In keeping with this determination, the AHA/ACC Guidelines recommend an invasive treatment strategy for patients with high-risk clinical predictors.^[22]

Table 5. AHA/ACC Recommendations for a Preferred Invasive Strategy (Open Table in a new window)

Patients at moderate to high risk for adverse events, such as persons with ST depression greater than 1 mm on ECG, troponin positivity or NQMI, or chest pain refractory to medical therapy, should be scheduled for cardiac catheterization with likely revascularization within the next 48 hours. The TACTICS/TIMI-18 trial showed that this early invasive strategy reduced 30-day rates of death, myocardial infarction, or rehospitalization for unstable angina from 19.4% to 15.9%.

FRISC II showed that even a delayed invasive strategy (mean time to revascularization 4 d, 71% revascularization rate vs 9% in the conservative arm) coupled with LMWH (dalteparin) therapy provides durable benefit for individual hard end points. At 1 year, the study’s invasive group had statistically significant reductions in myocardial infarction (8.6% vs 11.6%) and death (2.2% vs 3.9%), compared with the noninvasive group.^[21]

FRISC II (graphed below) has been the only randomized clinical trial able to show a mortality benefit. This was likely because of the very strict criteria for revascularization, which resulted in only 9% of the conservative arm receiving PCI or CABG. For example, in the TACTICS/TIMI-18 study and other North American trials, approximately 50% of the patients in the conservative arm had some form of revascularization, and not all patients in the invasive-strategy arm had indications for PCI or CABG. Therefore, the benefits of revascularization were less striking because of the narrower differences in rates of revascularization.

Of note, by 1 year, a catch-up phenomenon was observed in patients who had initial conservative management. By then, 52% had undergone angiography, and 43% required revascularization. See the image below.

Cost-to-benefit ratio of revascularization

The cost-to-benefit ratio of an initial invasive approach based on the FRISC II trial has been estimated. At the cost of 15 extra CABG and 21 PCI procedures, the benefit per 100 patients per year is as follows:

• 1.7 lives saved
• 2 myocardial infarctions prevented
• 20 readmissions prevented
• Earlier and better symptom relief

CABG is usually the preferred method for revascularization in patients with the following conditions:

• Left main trunk artery stenosis
• Poor left ventricular function
• Significant 3-vessel coronary artery disease or 2-vessel disease that involves the proximal left anterior descending artery
• Diabetes mellitus with focal stenosis in more than 1 vessel
• Concomitant severe valvular disease that requires open heart surgery

Patient monitoring

Continuous observation by Holter monitoring can provide helpful information. Depending on the criteria of ST-segment deviation, the timing of monitoring relative to disease instability, and the intervening medical therapy incidence of abnormal ST-segment shifts, has been reported at 11-66% in unstable angina. As many as 92% of these abnormal ST-segment shifts are asymptomatic, and more importantly, patients experiencing such episodes had an associated higher adverse event rate than those without (48% vs 20%, respectively).

Other studies have documented unfavorable outcomes at up to 6 months with the presence of at least 1 hour of silent ischemia during initial admission.

Follow-up

The ACC/AHA 2007 UA/NSTEMI guideline recommends that aspirin (75-162 mg/d) be continued indefinitely for patients with UA/NSTEMI who tolerate it.^[22]

For patients with UA/NSTEMI who are treated medically without stenting, clopidogrel (75 mg/d) should be prescribed for at least 1 month and ideally for up to 1 year.^[22]

The 2011 update to the ACCF/AHA guideline for UA/NSTEMI states that for patients treated with PCI, clopidogrel or prasugrel (10 mg/d) should be given for at least 12 months. For post-PCI patients with a drug-eluting stent, clinicians may consider continuation of clopidogrel or prasugrel beyond 15 months.^[12]

Unstable angina may require patients to take nothing orally if stress testing or an invasive procedure is anticipated. Otherwise, a diet low in cholesterol and saturated fat is recommended. Sodium restriction should be instituted for patients with heart failure or hypertension.

One to 3 months after the acute phase of unstable angina, the risk of major adverse events typically declines to that for patients with chronic stable angina. The goal is to prepare patients for resumption of their normal activities as safely as possible, to preserve left ventricular function, and to prevent future events.

Although secondary prevention is the responsibility of the primary care provider and the cardiologist, some centers have specialized teams (eg, cardiac rehabilitation, preventive services) that offer more intensive, and perhaps more effective, counseling and follow-up.

Smoking cessation

Aggressive attempts should be made to convince the patient and the rest of his/her household to cease smoking. The target is complete abstinence by patient and cohabitants from all tobacco products for 12 months or more. If the patient has expressed a decision to quit, he/she should be supported with counseling, follow-up, and pharmacotherapy, acupuncture, or hypnosis (if necessary). Patients should avoid secondhand smoke.

Lipid lowering

The target is LDL-C of 70 mg/dL or less, HDL-C of over 35 mg/dL, and triglycerides below 200 mg/dL. Diet modification, exercise, and drug therapy are indicated as per National Cholesterol Education Program (NCEP) guidelines.

Control of hypertension

The target is below 140/90 mm Hg or below 130/80 mm Hg if the patient has diabetes mellitus or chronic kidney disease. Diet modification, moderation of sodium and alcohol intake, exercise, smoking cessation, and pharmacotherapy are indicated.

Diabetes mellitus management

The ACCF/AHA 2011 update to the UA/NSTEMI guideline states that it is reasonable to achieve and maintain glucose levels less than 180 mg/dL for hospitalized patients, avoiding hypoglycemia. Thereafter, the guideline defers to the 2010 American Diabetes Association standard of care guideline.^{[12, 23]} Diet modification, exercise, pharmacotherapy (including ACE-inhibitor administration), preventive counseling regarding foot care, and ophthalmic examinations are indicated.

Weight management and nutritional counseling

The target is a body mass index (BMI) below 25 kg/m², as well as a waist circumference of less than 40 inches in men and of less than 35 inches in women. Diet modification and adequate intake of fruits and vegetables, exercise, and behavioral modification and counseling are indicated.

Psychosocial management

The target is lifestyle modification, recognition and treatment of substance abuse (alcohol or psychotropics) and depression or hostile attitude, and compliance with health maintenance. Education, counseling, support groups, and social or religious resources are indicated.

Activity management

Patients at risk for myocardial infarction should avoid sudden strenuous activities, especially in cold weather (eg, shoveling snow).

Consultation with a cardiologist is indicated to assist in risk stratification and decision making, to expedite further cardiac testing (eg, echocardiography, stress testing, angiography), and to treat unstable patients. A critical care or telemetry unit specialist is helpful for acute care and monitoring. A cardiothoracic surgeon is indicated when CABG is necessary.