Acute coronary syndromes without ST segment elevation

How are acute coronary syndromes classified?

Until recently, the two typical clinical presentations were generally referred to as unstable angina and acute myocardial infarction. A diagnosis of acute myocardial infarction requires evidence of myocardial necrosis. Whether myocardial infarction (that is, necrosis of cardiac muscle) is present usually becomes clear at a later stage, on the basis of laboratory tests (elevation of markers such as creatine kinase MB or cardiac troponins) or on the electrocardiogram (loss of QRS voltage or development of pathological Q waves). Because of the therapeutic decisions that need to be made on admission of patients with acute chest pain, before myocardial necrosis may be detected, new terms for the admission diagnosis have been introduced. These are based primarily on the findings on the admission electrocardiogram (table⇓).

If ST segment elevation (suggestive of transmural ischaemia) is present, a diagnosis of ST segment elevation acute coronary syndrome is made. These patients have an indication for urgent reperfusion treatment, either by percutaneous coronary intervention or by administration of a thrombolytic agent. If no ST segment elevations are present (normal or depressed ST segments or T wave inversion), a diagnosis of non-ST segment elevation acute coronary syndrome is made. If myocardial necrosis is documented, as indicated above, a discharge diagnosis of ST segment elevation myocardial infarction or non-ST segment elevation myocardial infarction is made. According to current guidelines, any elevation of cardiac markers qualifies as a myocardial infarction.3 Depending on the development of the electrocardiogram after admission, myocardial infarction may be subclassified as Q wave or non-Q wave myocardial infarction. If no evidence of myocardial necrosis exists, a discharge diagnosis of acute coronary syndrome or unstable angina is generally used. In this review, we focus on non-ST segment elevation acute coronary syndrome.

Sources and selection criteria

Acute coronary syndromes represent one of the most intensively studied topics in clinical research. Current guidelines and practice are based on a very large body of evidence, a summary of which is beyond the scope of this review. Our information came from personal archives and searches of Medline with the key words “acute coronary syndrome” and “unstable angina”. We used current guidelines on the management of acute coronary syndromes and searched for relevant Cochrane reviews.

How is acute coronary syndrome diagnosed?

The main initial diagnostic challenge is to differentiate acute coronary syndromes from non-cardiac chest pain. The assessment requires a thorough history (including analysis of risk factors), a physical examination, and, often, an electrocardiogram and determination of serum cardiac “markers” (troponin T, troponin I, creatine kinase MB isoenzyme). The most important determinant is the patient's history.4 Symptoms of acute coronary syndrome include substernal chest pain, radiating to the arms, the jaw, the neck, the back, or even the abdomen, which may be accompanied by nausea, vomiting, dyspnoea, and diaphoresis. Some patients may present without chest pain, and dyspnoea may be the only complaint.5 Typical chest pain that occurs suddenly at rest, particularly in a young patient, may suggest acute coronary spasm, which is sometimes associated with the use of cocaine or methamphetamine. Abnormalities on physical examination are usually absent but may include signs of heart failure, such as rales or oedema, hypotension, excessive sweating, or new mitral regurgitation.

Patients suspected of having acute coronary syndrome should be referred to a hospital for observation, electrocardiography, and blood testing (cardiac markers). Importantly, a normal electrocardiogram does not rule out acute coronary syndrome (although it does make it less likely), particularly if documented after relief of symptoms. In addition, normal concentrations of cardiac markers do not rule out acute coronary syndrome, particularly if measured shortly after the onset of complaints. Elevation of these markers takes four to six hours after myocardial necrosis, and six to eight hours are needed before markers of necrosis appear in peripheral blood. If an initial blood test is normal, and the history is highly suggestive, most clinicians do a second test after eight to 12 hours. If this is also normal, and the electrocardiogram is normal or shows little acute evolution, then the patient is at very low risk and may be discharged. However, such patients should have an early stress test to document whether provoked ischaemia is present. If the cardiac biomarkers are raised or the electrocardiogram shows evolutionary changes, admission to hospital is indicated. Imaging techniques may support the diagnostic process by showing wall motion abnormalities (echocardiography, magnetic resonance imaging), ischaemia (nuclear perfusion scanning), or coronary pathology (multislice computed tomography scanning). However, their role has not been firmly established.

How can we stratify risk in patients with acute coronary syndrome?

The in-hospital management of patients with chest pain is determined by the risk of complications and death. Indicators of high risk include typical complaints, documented coronary artery disease, and advanced age. On physical examination, new mitral regurgitation, hypotension, excessive sweating, pulmonary oedema, and rales are all associated with high risk.6 On the electrocardiogram, new Q waves, new ST segment deviation, or new T wave inversion with symptoms indicate high risk. Raised cardiac troponin T, troponin I, or creatine kinase MB in the serum indicates myocardial necrosis and a high risk of an adverse outcome. In addition, markers of congestive heart failure, particularly plasma B-type natriuretic peptide, have been shown to be independent predictors of death in patients with non-ST segment elevation acute coronary syndrome. For patients admitted with this diagnosis, several risk scores have been developed from clinical trials and registries.7 8 9 10 These can help to identify patients who are most likely to benefit from “invasive” treatment (coronary angiography and revascularisation). As patients included in trials represent a selected group of patients, risk models derived from unselected registries are probably more reliable in clinical practice (box).

How are patients managed in hospital?

The treatment of patients with non-ST segment elevation acute coronary syndrome, according to current guidelines, consists of two components: to alleviate the patient's complaints of pain and anxiety and to prevent recurrences of ischaemia and progression to (or to limit) myocardial infarction.11 12 This requires intensive antithrombotic treatment, and often an invasive strategy with coronary angiography followed by revascularisation if appropriate.

Drug treatment routinely includes β blockers, which reduce myocardial oxygen demand by reducing heart rate and blood pressure and reduce the risk of arrhythmias and recurrent ischaemia. Sedatives and analgesics may be used with the same goals, by reducing anxiety and pain. Vasodilators, such as nitrates and calcium channel blockers, are used to reduce the dynamic (spastic) component of coronary obstruction, and to lower blood pressure, but none of these drugs has been shown to reduce the risk of myocardial infarction or death.

Antithrombotic treatment

Revascularisation

Debate is ongoing as to whether all patients with non-ST segment elevation acute coronary syndrome should have coronary angiography followed by revascularisation (if indicated and if possible) or whether this should be done selectively in patients at high risk or in those who are refractory to medical treatment. Another question that remains unanswered is whether an initial period of stabilisation (“cooling down”) before proceeding to the catheterisation laboratory is beneficial or whether invasive treatment should be done as soon as possible. Although this question has not been studied in randomised trials, several studies have compared an invasive approach to a more “conservative” approach. In a meta-analysis published in 2005, including seven trials and 9212 patients, a routine invasive strategy exceeded a selective invasive strategy in reducing myocardial infarction, severe angina, and readmission to hospital over a mean follow-up of 17 months.20 Routine intervention was associated with a higher early mortality hazard and a trend towards a reduction in mortality during longer term follow-up. However, a subsequent randomised study in 1200 high risk patients with non-ST segment elevation acute coronary syndrome who received optimal medical treatment according to current guidelines found no significant difference in the combined endpoint of death, myocardial infarction, or readmission to hospital at one year follow-up.21 This suggests that if medical treatment is optimised, a routine invasive approach may not be necessary. A recent Cochrane review, including all trials published to date, concluded that an invasive strategy in unstable angina/non-ST segment elevation myocardial infarction results in a significant 33% relative risk reduction for both the end points of refractory angina and readmission to hospital at six to 12 months.22 However, this analysis includes the older trials in which medical treatment was probably less effective.

Current guidelines do recommend an invasive strategy in patients at high risk.11 12 If initially a conservative approach is selected—for example, in patients at lower risk—the patient should be closely monitored for recurrent chest pain or signs of ischaemia, using repeat electrocardiograms, monitoring of the ST segment, and serial measurements of the cardiac markers (creatine kinase MB, troponin). Even in the absence of such signs, the patient may have significant coronary artery disease. Predischarge stress testing is therefore generally done to determine if the patient is stable and whether significant coronary obstructions remain. Alternatively, high risk patients should be considered for angiography and appropriate revascularisation during the initial admission.

What is appropriate long term treatment?

After discharge, management of patients with acute coronary syndromes consists of two main components. Firstly, prevention of recurrent ischaemia and death requires continued treatment with aspirin (indefinitely), clopidogrel (at least 9-12 months),14 and β blockers. Secondly, the underlying atherosclerotic process should be treated by tackling all modifiable risk factors.23 24 These include the routine use of a statin to lower plasma low density lipoprotein cholesterol concentrations, use of angiotensin converting enzyme inhibitors,25 strict treatment of hypertension and diabetes, cessation of smoking, achieving an optimal body weight, regular physical exercise, and healthy food choices.