Acute coronary syndrome (defined here as unstable angina and non-ST elevation myocardial infarction [MI]) is characterized by episodes of chest pain at rest or with minimal exertion that are increasing in frequency or severity, often with dynamic electrocardiography (ECG) changes.

• Aspirin reduces the risk of death, MI, and stroke compared with placebo in persons with acute coronary syndrome at dosages up to 325 mg daily. Higher dosages of aspirin are no more effective and increase the risk of complications.

• Adding clopidogrel to aspirin may reduce the combined outcome of mortality and MI, but may increase the risk of bleeding.

• Intravenous glycoprotein IIb/IIIa platelet receptor inhibitors reduce the combined end point of death and MI at six months in persons with acute coronary syndrome, but increase the risk of bleeding.

• Unfractionated or low-molecular-weight heparin plus aspirin may reduce death or MI at one week, but longer-term benefits are unclear.

• Low-molecular-weight heparin may reduce MI compared with unfractionated heparin.

• Direct thrombin inhibitors (hirudin and bivalirudin) may reduce death or MI compared with unfractionated heparin.

• Warfarin has not been shown to be beneficial and increases the risk of major bleeding.

We do not know whether intravenous nitrates, beta blockers, or calcium channel blockers reduce the risk of MI or death, although they may reduce the frequency and severity of chest pain.

CAUTION: Short-acting dihydropyridine calcium channel blockers may increase mortality in persons with congenital heart disease.

Early, routine cardiac catheterization and revascularization may reduce death and nonfatal MI compared with conservative strategies (medical treatment with or without subsequent cardiac catheterization and revascularization).

Definition

Acute coronary syndrome encompasses unstable angina, non-ST elevation MI (new term for non-Q wave MI, often referred to as non-STEMI), and ST elevation MI (new term for Q wave MI, often referred to as STEMI). Unstable angina and non-STEMI are overlapping entities and will be discussed together in this review. STEMI is not discussed in this review.

Unstable angina with non-STEMI is a spectrum of disease that involves an imbalance of supply and demand of oxygen available to the myocardium. This causes symptoms such as new-onset exertional angina, preexisting angina that is refractory to nitroglycerin, or angina at rest. The pathophysiology governing anginal symptoms is usually caused by atherosclerotic plaque that nearly obstructs coronary vessels. The distinguishing feature between unstable angina and non-STEMI is the presence of elevated cardiac markers, such as troponin, which implies myocardial damage. Patient history alone is insufficient to make a diagnosis of acute coronary syndrome. The clinical dilemma of distinguishing between cardiac and noncardiac pain requires a combination of patient history, ECG, and biomarkers.

Overlapping clinical entities in the acute coronary syndrome spectrum of disease allow for similar treatment strategies, and many trials include persons with either unstable angina or non-STEMI. We have included systematic reviews and randomized controlled trials in a mixed population of persons with unstable angina, non-STEMI, or both, which we will refer to here as acute coronary syndrome.

Incidence

In the United States, acute coronary syndrome accounts for more than 1.4 million hospital admissions per year. In industrialized countries, the annual incidence of unstable angina is about six out of 10,000 persons in the general population.

Etiology and Risk Factors

Risk factors are the same as for other manifestations of ischemic heart disease—older age, previous atheromatous cardiovascular disease, diabetes, smoking, hypertension, hypercholesterolemia, male sex, and a family history of premature ischemic heart disease. It can also occur in association with other disorders of circulation, including valvular disease, arrhythmias, and cardiomyopathies.

Prognosis

Between 9 and 19 percent of persons with acute coronary syndrome die in the first six months after diagnosis, with about one half of these deaths occurring within 30 days of diagnosis. Several risk factors may indicate poor prognosis and include severity of presentation (e.g., duration of pain, speed of progression, evidence of heart failure); medical history (e.g., previous acute coronary syndrome, acute MI, left ventricular dysfunction), other clinical parameters (e.g., age, diabetes), ECG changes (e.g., severity of ST segment depression and deep T wave inversion), biomarkers (e.g., presence of troponin concentration elevation), and change in clinical status (e.g., recurrent chest pain, silent ischemia, hemodynamic instability).

However, several key prognostic indicators associated with adverse outcomes may be used to aid clinical decision making. Variables, including age 65 years or older, at least three risk factors for coronary artery disease, known significant coronary stenosis, degree of ST segment deviation, recurrent anginal symptoms in 24 hours, use of aspirin in past seven days, and elevated cardiac biomarkers, can be used to generate a scoring system to identify high-risk patients who may experience true ischemic cardiac events and death (thrombolysis in MI risk score). The more of these factors that are present, the greater the likelihood of adverse ischemic events. This helps stratify patients according to risk and identify high-risk patients.