Acute Coronary Syndromes—Tailoring Treatment Based on Risk Stratification

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Approximately five million people present to the emergency department (ED) each year with chest pain, and billions of dollars are spent on assessment and treatment. Many therapies are time-dependent, so rapid identification of patients with acute coronary syndrome (ACS) - unstable angina (UA) and acute myocardial infarction (MI) - at high risk for adverse outcomes is essential. Missed or inappropriately treated ACS carries important medicolegal consequences. This raises the issue of whether doctors should treat as many people as quickly as they can. As few as 10% to 30% of patients who present with symptoms of ACS subsequently prove to have ACS. As the proportion of patients with actual disease decreases, the benefits of the treatment decrease, while the number of adverse outcomes remains constant or potentially increases (if some patients have aortic dissection, for example).This article reviews the risk assessment and resultant management of patients with UA and non-ST-elevation MI (UA/NSTEMI). A treatment algorithm that evaluates the differences in UA/NSTEMI patients and those with STEMI will also be reviewed.

Risk Stratification

Acute MI is described as a rise and fall of serum cardiac markers, preferably troponin, and either ischemic symptoms, ischemic electrocardiogram (ECG) changes, or previous percutaneous coronary intervention (PCI). Angina is defined as discomfort that is induced by exercise and relieved by rest or nitroglycerine administration, and is classified according to severity, with class 3 angina occurring after walking one or two blocks or climbing one flight of steps. Unstable angina is defined as class 3 angina that is either new onset exertional angina, or increasing within the past two months, or occurring at rest for more than 20 minutes. As mentioned, the prevalence of actual ACS is much lower than the number of ED patients suspected of having ACS. The Multicenter Chest Pain Study showed that, between 1984 and 1986, 26% of patients admitted for possible ACS had acute MI and 28% had unstable angina. With greater recognition of missed disease by both the public and the medical community, however, these rates have declined. The same study found that, between 1990 and 1994, only 11% of these patients had acute MI and 33% had unstable angina. The American Heart Association (AHA)/American College of Cardiology (ACC) risk stratification guidelines are shown in Tables 1 and 2. Generally, they involve a determination of:

  • whether the signs and symptoms of ACS are due to coronary artery disease (CAD); and
  • the risk of adverse events.

History, examination, ECG, and cardiac markers are used to categorize the patient with definite ACS, possible ACS, chronic stable angina, or a non-cardiac process. However, this approach has many limitations, including the practicality of using the suggested 28 elements to determine whether ACS symptoms are due to CAD and the 24 parameters to determine the risk of adverse events in the presence of ACS. Application of this approach can also yield perplexing results. A 35-year-old male with burning epigastric pain radiating to the chest for 25 minutes that is improved but not resolved in the ED with an antacid and with normal ECG and cardiac markers would be classified according to the guidelines as having intermediate risk of ACS due to CAD and a high risk of adverse events due to prolonged duration of chest pain at rest. In addition, most of the AHA/ACC risk stratification criteria are based on chest pain, but up to half of all acute MIs present without chest pain.

The larger problem is that symptoms predicting risk in patients who actually have disease are different to those that predict risk among patients with suspected disease. For example, pain radiating to the neck, jaw, or left arm in a patient suspected of having cardiac ischemia does not predict risk of major adverse outcomes, but it does predict risk of acute MI. Similarly, T-wave inversions do not predict adverse outcomes in a patient with suspected ischemia but do predict adverse outcomes in patients with confirmed acute MI.

The use of decision rules in general have not been shown to improve admission or discharge decision-making. However, they may be helpful in improving decision-making in inexperienced physicians.

An Alternative Approach

A simpler approach may be to determine whether they have the disease or not. Definite ACS can be diagnosed when confirmatory signs are seen, such as ischemia on ECG or diagnostic cardiac markers. For example, even in a patient with an atypical story, the presence of planar ST depression would confirm ischemia. Probable ACS, or disease that is strongly suspected but not yet identified, can be considered when a patient has:

  • a concerning story;
  • abnormal but non-diagnostic ECG, such as ST segments or T-waves that are changed from a previous ECG; or
  • minimal but non-diagnostic elevation of cardiac markers (e.g.TnI=0.2 when 1.5 is diagnostic, or a 65-year-old male with chest pressure at rest radiating to the left arm and relieved with nitroglycerin, recent onset of exertional symptoms, and a non-specific ECG).

Patients who probably do not have ACS would include those atypical symptoms, an ECG lacking signs of ischemia or left bundle-branch block, and negative cardiac markers. This would apply to a 65-year-old man with previous coronary artery bypass graft (CABG), current sharp chest pains lasting seconds and not relieved with nitroglycerin, and an unchanged ECG.

ED physicians should also be aware of patient characteristics that increase risk such as advanced age, male sex, prior MI, known vascular disease, and diabetes. Ischemic ST-segment depression or elevation, or T-wave abnormalities, along with changes from previous ECGs, are important. Consideration of symptoms that increase the risk of ACS is important in decision-making and these include pain that is substernal, pressure-like, radiates, is similar to that experienced with a previous MI, worsens with exertion, and is not relieved by rest or nitrates. Other MI presentations such as syncope, shortness of breath (SOB), dizziness, and upper abdominal pain must also be considered.

Cardiac markers can be used to rule out acute MI when they are sampled over 18 hours. However, they can be used in an accelerated protocol to rule out acute MI in the low-risk patient. They cannot be used to rule out unstable angina. Elevations of cardiac markers above normal define acute MI. However, any patient with detectable troponin should be considered at increased risk. The American College of Emergency Physicians (ACEP's) policy for obtaining cardiac marker levels is to evaluate CK-MB mass and subforms at six to 10 hours from pain onset and cTnT and cTnI at eight to 12 hours. A baseline and second level of the markers is recommended.

Treatment and Risks

Selecting the appropriate treatment can be challenging when relying on clinical trial data, especially because the medications conferring the most benefit in the ACS patient population also have the potential for the most harm, primarily due to increased bleeding. Therefore, it is most prudent to consider each medication in terms of the number needed to treat (NNT) to prevent one mortality or morbidity case, versus the number needed to harm (NNH) - or the number of patients who will receive the medication before an adverse event is expected.

Uses, benefits, and risks of treatments for ACS associated with significant benefit as well as greater risk of bleeding are described below.


Heparin (intravenous (IV) unfractionated or low molecular weight heparin (LMWH)) is recommended for patients with suspected MI and UA with an NNT of 30 to 40 and an NNH of 70 to 90.However, these trials were performed in patients with positive cardiac markers or ischemic ECGs. It is not clear that these results can be extrapolated to patients without these findings of definite disease. LMWH appears to have slightly fewer adverse outcomes than IV unfractionated heparin. Dosing for IV unfractionated heparin is 60-70U/kg (maximum 5,000U) and 12-15U/kg/hour infusion (maximum 1,000U/hour). For LMWH, dosing for enoxaparin is 1mg/kg subcutaneous (SQ) twice-daily (bid) and for dalteparin, 120IU/kg SQ bid.

Glycoprotein 2b3a Inhibitors

Glycoprotein 2b3a inhibitors include abciximab for PCI only, and eptifibatide and tirofiban for both ACS and PCI. They are clearly beneficial in patients undergoing PCI, whether electively or for ACS with an NNT of 20 to 30. They are also suggested in patients with continuing ischemia, elevated troponin, and other high-risk features such as age over 75 years and accelerating symptoms. This is in spite of the fact that a meta-analysis of almost 20,000 patients with ACS who did not receive PCI showed no benefit from treatment with these agents.