Unstable Angina

Most clinicians use the term “unstable angina” to denote an accelerating or “crescendo” pattern of pain in cases where previously stable angina occurs with less exertion or at rest, lasts longer, and is less responsive to medication. Coronary angioscopy has shown that a high proportion of patients with this pattern of symptoms have “complex” coronary stenoses characterized by plaque rupture, ulceration, or hemorrhage with subsequent thrombus formation. This inherently unstable situation may progress to complete occlusion and infarction or may heal, with reendothelialization and a return to a stable though possibly more severe pattern of ischemia. New-onset angina is sometimes considered unstable, but if it is exertional and responsive to rest and medication, it does not carry the same poor prognosis.

Most patients with unstable angina will exhibit electrocardiographic changes during pain - commonly ST segment depression or T wave flattening or inversion but sometimes, and more ominously, ST segment elevation. They may exhibit signs of left ventricular dysfunction during pain and for a time thereafter.

Chest pain is one of the most frequent reasons for emergency department visits, and the consequences of misdiagnosis are significant (clinically for false-negative diagnoses and economically for false-positives). Up to half of patients have noncardiac diagnoses, and even many of those with coronary disease are at low risk for early events (< 1% 30-day event rate). However, those with recent, prolonged, or recurrent episodes and accompanying electrocardiographic changes indicative of ischemia (ST segment depression > 1 mm, ischemic ST segment elevation, T wave inversions, or new LBBB) may have much higher event rates. Many hospitals have developed chest pain observation units to provide a longer period of observation and immediate testing in patients determined to be at low risk in order to improve the triage process. In many cases those who have not experienced new chest pain and have no electrocardiographic changes or cardiac enzyme elevations undergo treadmill exercise tests or imaging procedures to exclude ischemia at the end of a 6-24 hour period and are discharged directly from the emergency department if these tests are negative.


A. General Measures
Treatment of unstable angina should be multifaceted and vigorous. Patients should be hospitalized, maintained at bed rest or at very limited activity, monitored, and given supplemental oxygen. Sedation with a benzodiazepine agent may help if anxiety is present. The systolic blood pressure is usually maintained at 100-120 mm Hg, except in previously severe hypertensives, and the heart rate should be lowered to 60/min.

B. Anticoagulation, Antiplatelet, and Thrombolytic Therapy
Because intravascular thrombosis plays a prominent role in the pathophysiology of unstable angina and its progression to myocardial infarction, antithrombotic therapy is an important part of treatment for unstable angina. Most patients should receive a combination of two or more agents. Aspirin, 325 mg daily, should be commenced on admission, and intravenous heparin should be started if symptoms have been recent (past 24 hours) or if they recur. Heparin therapy, when necessary, should be continued for at least 2 days. Several trials have shown that low-molecular-weight heparin is marginally superior to unfractionated heparin in preventing recurrent ischemic events in the setting of acute coronary syndromes. Enoxaparin (1 mg/kg subcutaneously every 12 hours) is the best-studied member of this class of agents. The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial demonstrated a 20% reduction in the composite end point of cardiovascular death, myocardial infarction, and stroke with the addition of clopidogrel (300 mg loading dose, 75 mg daily for 12 months) in patients with non-ST segment elevation acute coronary syndromes.

The administration of drugs that block the platelet glycoprotein IIb/IIIa receptor is a useful adjunct in high-risk patients (usually defined by fluctuating ST segment depression or positive biomarkers) with unstable angina, particularly when they are undergoing PTCA or stenting. The short-acting small molecule inhibitors have been the best-studied agents in the nonintervention setting. Both tirofiban, 0.4 ug/kg/ min for 30 minutes followed by 0.1 ug/kg/min, and eptifibatide, 180 ug/kg bolus followed by a continuous infusion of 0.1 ug/kg/min, have been shown to be effective in unstable angina and non-Q wave myocardial infarction when added to heparin. Downward dose adjustments are required in patients with reduced renal function.

Since in unstable angina the vessel usually remains patent and the thrombi are undergoing continuous spontaneous formation and thrombolysis, thrombolytic therapy has not been effective in improving the outcome.

C. Nitroglycerin
The nitrates are first-line anti-ischemic therapy for unstable angina. Nonparenteral therapy with sublingual or oral agents or nitroglycerin ointment is usually sufficient. If pain persists or recurs, intravenous nitroglycerin should be started. The usual initial dosage is 10 ug/min. The dosage should be titrated to 1 ug/kg/min over 30-60 minutes and further increased as tolerated if pain recurs. Dosages up to 10 ug/kg/min or higher may be used. Tolerance to continuous nitrate infusion is common. Careful - usually continuous - blood pressure monitoring is required when intravenous nitroglycerin is used.

D. Beta-Blockers
These agents are also a part of the initial treatment of unstable angina unless otherwise contraindicated. If the patient has no physical findings of heart failure, these agents can usually be started without measurements of left ventricular function. Patients with evidence of large or multiple old infarctions are an exception. The pharmacology of these agents is discussed in here and summarized in Table 11-6. Use of agents with intrinsic sympathomimetic activity should be avoided in this setting. The goal of acute treatment is to reduce the heart rate below 60-70/min. Oral medication is adequate in most patients, but intravenous treatment with metoprolol, given as three 5- mg doses 5 minutes apart, achieves a more rapid effect. Oral therapy should be aggressively titrated upward as blood pressure permits.

E. Calcium Channel Blockers
Calcium channel blockers have not been shown to favorably affect outcome in unstable angina, and they should be used primarily as third-line therapy in patients with continuing symptoms on nitrates and beta-blockers or those who are not candidates for these drugs. In the presence of nitrates and without accompanying beta-blockers, diltiazem or verapamil is preferred, since nifedipine and the other dihydropyridines are more likely to cause reflex tachycardia or hypotension. The initial dosage should be low, but upward titration should proceed rapidly.

F. Intra-aortic Balloon Counterpulsation (IABC)
IABC can both reduce myocardial energy requirements (systolic unloading) and improve diastolic coronary blood flow. This approach is sometimes employed to stabilize patients prior to angiography or revascularization, but with modern techniques it is rarely necessary.

Prognosis & Indications for Revascularization

Over 90% of patients can be rendered pain-free with these measures. Patients who do not become ischemia-free on medical therapy should have early coronary arteriography and revascularization. Controlled trials have reported mixed results as to whether a strategy of routine coronary angiography and revascularization is superior to aggressive medical therapy and selective revascularization in patients with recurrent ischemia or very positive stress tests. Recent trials that have employed both platelet glycoprotein IIb/IIIa antagonists and stents in the majority of patients have favored an early but not necessarily immediate invasive strategy (eg, within several days and prior to discharge). Depending on the stringency of the definition of unstable angina, 10-30% of patients will have an early infarction, and the 1-year mortality rate is 10-20%. Elevated troponin I or T concentrations and “silent” ST segment shifts have both identified patients at higher risk for subsequent myocardial infarction or recurrence of severe ischemia. These markers identify a subset of patients who benefit from the early use of glycoprotein IIb/IIIa receptor antagonists and, most likely, early revascularization.

Because recurrent episodes, infarction, and sudden death may occur following relief of unstable angina, additional evaluations should be performed in patients who have been stabilized, consisting of either (1) early exercise or pharmacologic stress testing to identify high-risk subsets for further invasive evaluation, or (2) coronary arteriography. The choice of approach should be individualized based on the patient’s age and general health as well as the severity of symptoms and signs of ischemia. The artery responsible for the ischemia can usually be determined from electrocardiographic or scintigraphic changes during pain, and the lesion is often amenable to PTCA. If revascularization is not performed, long-term management is the same as that outlined for stable angina pectoris.

ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-summary article. J Am Coll Cardiol 2002;40:1366.

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Boden WE et al: Optimizing management of non-ST segment elevation acute coronary syndromes. J Am Coll Cardiol 2003;41(Suppl):1S.

Boersma E et al: Platelet glycoprotein IIb/IIIa inhibitors in acute coronary syndromes: a meta-analysis of all major randomised clinical trials. Lancet 2002;359:189.

Cannon CP et al: Comparison of early invasive and conservative strategies in patients with unstable coronary syndromes treated with the glycoprotein IIb/IIIa inhibitor tirofiban. N Engl J Med 2001;344:1879.

de Feyter PJ et al: Bypass surgery versus stenting for the treatment of multivessel disease in patients with unstable angina compared with stable angina. Circulation 2002;105:2367.

Fox KA et al: Interventional versus conservative treatment for patients with unstable angina or non-ST-elevation myocardial infarction: the British Heart Foundation RITA 3 randomised trial. Lancet 2002;360:743.

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Levine GN et al: Antithrombotic therapy in patients with acute coronary syndromes. Arch Intern Med 2001;161:937.

Mahoney EM et al: Cost and cost-effectiveness of an early invasive vs conservative strategy for the treatment of unstable angina and non-ST-segment elevation myocardial infarction. JAMA 2002;288:1851.

Udelson JE et al: Myocardial perfusion imaging for evaluation and triage of patients with suspected acute cardiac ischemia: a randomized controlled trial. JAMA 2002;288:2693.

Wong GC et al: Use of low-molecular-weight heparins in the management of acute coronary artery syndromes and percutaneous coronary intervention. JAMA 2003;289:331.

Yusuf S et al: Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494.

Acute Myocardial Infarction

Essentials of Diagnosis
General Considerations
Clinical Findings

  A. Symptoms
  B. Signs
  C. Laboratory Findings
  D. Electrocardiography
  E. Chest X-Ray
  F. Echocardiography
  G. Scintigraphic Studies
  H. Hemodynamic Measurements


  A. Aspirin
  B. Thrombolytic Therapy
  C. Acute PTCA and Stenting for ST Segment Elevation Myocardial Infarction
  D. Initial Management of Non-ST-Segment Elevation Myocardial Infarction
  E. General Measures
  F. Analgesia
  G. Beta-Adrenergic Blocking Agents
  H. Nitrates
  I. Angiotensin-Converting Enzyme (ACE) Inhibitors
  J. Antiarrhythmic Prophylaxis
  K. Calcium Channel Blockers
  L. Anticoagulation


  A. Postinfarction Ischemia
  B. Arrhythmias
  C. Myocardial Dysfunction
  D. Right Ventricular Infarction
  E. Mechanical Defects
  F. Myocardial Rupture
  G. Left Ventricular Aneurysm
  H. Pericarditis
  I. Mural Thrombus

Postinfarction Management

  A. Risk Stratification
  B. Secondary Prevention
  C. ACE Inhibitors in Patients With Left Ventricular Dysfunction
  D. Revascularization

Provided by ArmMed Media
Revision date: June 22, 2011
Last revised: by Sebastian Scheller, MD, ScD