Overview of the acute management of unstable angina and non-ST elevation myocardial infarction

Authors
Jeffrey A Breall, MD, PhD
Julian M Aroesty, MD
Michael Simons, MD
Section Editors
Christopher P Cannon, MD
James Hoekstra, MD
Donald Cutlip, MD
Deputy Editor
Gordon M Saperia, MD, FACC
Disclosures
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2013. | This topic last updated: Apr 11, 2012.
INTRODUCTION Unstable angina (UA), acute non-ST elevation myocardial infarction (NSTEMI), and
acute ST elevation myocardial infarction (STEMI) are the three presentations of acute coronary
syndromes (ACS). The first step in the management of patients ACS is prompt recognition, since the
beneficial effects of therapy are greatest when performed soon after hospital presentation. For patients
presenting to the emergency department with chest pain suspicious for an ACS, the diagnosis of
myocardial infarction can be confirmed by the ECG and serum cardiac biomarker elevation; the history is
relied upon heavily to make the diagnosis of unstable angina. (See"Criteria for the diagnosis of acute
myocardial infarction" and "Initial evaluation and management of suspected acute coronary syndrome in
the emergency department".)
Once the diagnosis of either UA or an acute NSTEMI is made, the acute management of the patient
involves the simultaneous achievement of several goals [1,2]:

Relief of ischemic pain. (See 'Initial medical therapy' below.)

Assessment of the patient's hemodynamic status and correction of abnormalities. Hypertension

and tachycardia, both of which will markedly increase myocardial oxygen consumption
requirements, may be managed with beta blockers and intravenous nitroglycerin.

Estimation of risk (see 'Early risk stratification' below).

Choice of a management strategy, ie, an early invasive strategy (with angiography and intent for
revascularization with PCI or CABG as defined by the anatomy) versus a conservative strategy
with medical therapy. (See 'Immediate angiography and revascularization' below.)

Initiation of antithrombotic therapy (including antiplatelet and anticoagulant therapies) to prevent

further thrombosis of or embolism from an ulcerated plaque.

Beta blocker therapy to prevent recurrent ischemia and life-threatening ventricular arrhythmias

The acute management goals should be followed by the administration of different drugs that may
improve the long-term prognosis [1]. Some of these therapies include:

Long-term antiplatelet therapy to reduce the risk of recurrent coronary artery thrombosis or, with
PCI, coronary artery stent thrombosis

Statins

Long-term oral anticoagulation in the presence of left ventricular thrombus or chronic atrial
fibrillation to prevent embolization

Possible use of an angiotensin converting enzyme (ACE) inhibitor in patients at increased risk

This topic will summarize emergent/early management issues for patients with UA or acute NSTEMI and
then direct the reader to a more detailed discussion in other topics. The management of the patient after a
revascularization strategy has been chosen and carried out is discussed separately. (See "Overview of
the non-acute management of unstable angina and non-ST elevation myocardial infarction".)
The management of the patient with ST elevation MI or with a complication of an acute MI (eg,
cardiogenic shock, mitral regurgitation, ventricular septal defect) is discussed separately. (See "Overview
of the acute management of ST elevation myocardial infarction" and "Prognosis and treatment of
cardiogenic shock complicating acute myocardial infarction" and "Mechanical complications of acute
myocardial infarction" and "Initial evaluation and management of suspected acute coronary syndrome in
the emergency department".)
GENERAL PRINCIPLES An increasing number of centers use structured algorithms, checklists, or
critical pathways to screen patients with a suspected ACS (algorithm 1) [3-8]. Many of these strategies
combine diagnostic evaluation, such as electrocardiography and serum biomarkers, with therapeutic
interventions, such as aspirin, beta blockers, antithrombotic agents, and, in most patients, early coronary
angiography and revascularization. (See "Initial evaluation and management of suspected acute coronary
syndrome in the emergency department".)
Definitions Among patients considered to have angina, there are three presentations of angina that
suggest an acute coronary syndrome (ACS) [1]:

Rest angina, which is usually more than 20 minutes in duration

New onset angina that markedly limits physical activity

Increasing angina that is more frequent, longer in duration, or occurs with less exertion than
previous angina

UA and NSTEMI differ primarily in whether the ischemia is severe enough to cause sufficient myocardial
damage to release detectable quantities of a marker of myocardial injury (troponins):

UA is considered to be present in patients with ischemic symptoms suggestive of an ACS and no

elevation in troponins, with or without ECG changes indicative of ischemia (eg, ST segment
depression or transient elevation or new T wave inversion).

NSTEMI is considered to be present in patients having the same manifestations as those in UA,
but in whom an elevation in troponins is present.

Since an elevation in troponins may not be detectable for hours after presentation, UA and NSTEMI are
frequently indistinguishable at initial evaluation. As a consequence, initial management is the same for

these two syndromes. For this reason, and because the pathogenetic mechanisms of the two conditions
are similar, they are often considered together. (See "Classification of unstable angina and non-ST
elevation myocardial infarction".)
Elderly patients It is estimated that 60 to 65 percent of MIs occur in patients 65 years of age and 33
percent occur in patients 75 years of age [9,10]. In addition, as many as 80 percent of all deaths related
to MI occur in persons 65 years of age.
Although patients age 75 and older have been underrepresented in clinical trials of ACS, the following
observations concerning acute MI in older adults compared to younger patients are generally accepted
[11]:

Elderly patients are more likely to have an NSTEMI rather than an STEMI.

Elderly patients more frequently have an atypical presentation, including silent or unrecognized
MI due to presenting symptoms of syncope, weakness, or confusion (delirium) [11,12]. Delays in
diagnosis have been well-documented and often lead to delays in therapy [11].

Patients 75 years of age have a higher in-hospital mortality (19 versus 5 percent in one series)
[13]. Both bleeding and recurrent MI are also more frequent [11]. (See'Importance of
dosing' below.)

Elderly patients are more likely to have heart failure associated with the MI (40 versus 14 percent
in one report), the risk for which increases progressively in each successive age group from 36
percent in those 65 to 69 years of age to 65 percent in those 85 years of age [14].

Some of the worse outcomes after acute MI probably result from comorbidities in elderly patients, but also
can be attributed in part to a lower likelihood of receiving potentially beneficial therapies due to concerns
about toxicity. Therapies such as beta blockers, percutaneous coronary intervention (PCI), or coronary
artery bypass grafting (CABG) are all utilized to a lesser degree in elderly patients [13-15].
A retrospective review of almost 57,000 patients with a non-ST elevation acute coronary syndrome found
that, after adjustment, patients (including those 75 years of age) who received more recommended
therapies had lower in-hospital mortality rates than those who did not [16]. Thus, although concern about
risks and side effects is appropriate and it is not clear that adjustment accounted for all risk factors, older
age alone should not be an indication to withhold recommended therapy.
The 2007 ACC/AHA guidelines recommended that elderly patients (defined as greater than 75 years of
age) with unstable angina pectoris and NSTEMI should receive the same treatment as younger patients
with the following cautions [1]:

The patient's general health, comorbidities, cognitive status, and life expectancy should be taken
into account.

Increased sensitivity to hypotension-inducing drugs and possible altered drug pharmacokinetics

should be considered. Calculation of the creatinine clearance is recommended for all patients 75
years of age at the time of initial care [11]. This calculation requires a stable serum creatinine
concentration. (See "Assessment of kidney function", section on 'Assessment of GFR'.)

Intensive medical and interventional management can be undertaken with close monitoring for
adverse effects.

Information of particular relevance to older adults will be mentioned throughout the remainder of this topic.
Cocaine associated myocardial infarction MI is a well-described complication among patients
presenting with cocaine-induced ischemic symptoms. (See "Evaluation and management of the
cardiovascular complications of cocaine abuse", section on 'Reperfusion and revascularization'.)
We agree with the 2008 American Heart Association scientific statement on the Management of cocaineassociated chest pain and myocardial infarction, which states that these patients should be managed in a
manner similar to other ACS patients [17].
The following two points were also made:

Benzodiazepines should be administered early

Beta blockers should not be used in the setting of acute cocaine intoxication with chest pain due
to the possibility of exacerbation of coronary artery vasoconstriction

INITIAL MEDICAL THERAPY Patients with UA or NSTEMI should be treated with an early medical
regimen similar to that used in a STEMI with one exception: there is no evidence of benefit (and possible
harm) from fibrinolysis. Initial therapy, which should be instituted within 20 minutes of presentation, is
discussed in detail separately. (See "Initial evaluation and management of suspected acute coronary
syndrome in the emergency department", section on 'Immediate ED interventions'.)
Drug metabolism is more likely to be reduced in elderly patients, particularly with regard to drugs that are
excreted by the kidney. Dose adjustment is necessary with GP IIb/IIIa inhibitors and unfractionated or low
molecular weight heparin, but not with aspirin and clopidogrel [11]. (See 'Elderly patients' above.)
Anti-ischemic and analgesic therapy
Oxygen We recommend supplemental oxygen for patients with an arterial saturation less than 90
percent, patients in respiratory distress, or those with other high risk features for hypoxemia [1].
The role of supplemental oxygen in patients without hypoxia has not been well-studied. A 2010 Cochrane
review evaluated three trials of 387 patients with presumed myocardial infarction (MI) who were randomly
assigned to supplemental oxygen or room air. Enrolled patients were either hypoxic and normoxic. The
study found no significant difference in mortality (pooled relative risk 2.88, [95% CI 0.88-9.39] in an
intention-to-treat analysis and 3.03, [95% CI 0.93-9.83] among those with confirmed MI). No subgroup
analysis was performed on those with normoxia [18].
The suggestion of harm with supplemental oxygen found in this Cochrane review is of concern,
particularly in patients with normoxia, as a pathophysiologic basis for such harm has been articulated [19].
Hyperoxia, which might occur with the administration of oxygen to normoxic individuals, has been shown
to have a direct vasoconstrictor effect on the coronary arteries [19].
Until better evidence to support the use of supplemental oxygen in normoxic patients with acute MI is
available, we suggest (a weak recommendation) its use.
Nitroglycerin Sublingual nitroglycerin is administered to patients presenting with ischemic type chest
pain, followed by intravenous nitroglycerin in patients with persistent pain after three sublingual

nitroglycerin tablets, hypertension, or heart failure. (See "Nitrates in the management of acute coronary
syndrome".)
Nitrates must be used with caution or avoided in settings in which hypotension is likely or could result in
serious hemodynamic decompensation, such as right ventricular infarction or severe aortic stenosis. In
addition, nitrates are contraindicated in patients who have taken a phosphodiesterase inhibitor for erectile
dysfunction within the previous 24 hours. (See "Sexual activity in patients with heart disease" and "Right
ventricular myocardial infarction", section on 'Optimization of right ventricular preload'.)
Morphine Intravenous morphine sulfate at an initial dose of 2 to 4 mg, with increments of 2 to 8 mg
repeated at 5 to 15 minute intervals, should be given for the relief of chest pain or anxiety.
Beta blockers Controlled trials have repeatedly documented the beneficial effects of beta blockers in
patients with acute myocardial infarction; however, there have been no randomized trials specifically
addressing the efficacy of these drugs in non-ST elevation ACS. (See "Beta blockers in the management
of acute coronary syndrome", section on 'Summary and recommendations'.)
Nevertheless, given the proven efficacy in unselected patients with an acute MI and the absence of harm
in NSTEMI or UA, the 2007 ACC/AHA guidelines recommended that beta blocker therapy should be
administered universally to all patients without contraindications [1]. Similar recommendations were made
by a 2004 task force of the European Society of Cardiology [20].
In our view, treatment should include early use of intravenous beta blockade in patients without
contraindications who have ongoing chest pain, hypertension, or tachycardia not caused by heart failure.
This approach is supported by the 2007 AHA scientific statement on hypertension [21]. A cardioselective
agent (metoprolol or atenolol) is preferred.
However, based upon the results of the COMMIT/CCS2 trial, the largest placebo-controlled trial ever
performed with beta blockers in acute MI, it seems reasonable to defer intravenous beta blockers in
patients who are hemodynamically compromised in whom mortality may actually be increased by such
therapy. Once the patient is stable, an oral beta blocker can be started with gradual uptitration to the
maintenance doses cited below. (See "Beta blockers in the management of acute coronary syndrome",
section on 'Early administration'.)
Statin therapy Statin therapy should be instituted prior to hospital discharge, with some data
supporting initiation at the time of diagnosis [1]. We recommend therapy with atorvastatin 80 mg/day,
which was used in the PROVE IT-TIMI 22 and MIRACL trials [22,23]. Among patients who were
previously treated with a different statin regimen, we suggest switching to atorvastatin 80 mg/day.
(See "Cholesterol lowering after an acute coronary syndrome", section on 'Continuation of prior statin
therapy'.)
Initial intensive statin therapy, rather than gradual dose titration upward, is recommended because of the
suggestion of benefit in the PROVE IT-TIMI 22 trial within 30 days [24], an interval before the first serum
cholesterol measurement on therapy would usually be obtained. (See "Cholesterol lowering after an acute
coronary syndrome".)
Based on these recommendations, most patients should have a lipid profile performed early in their
hospitalization, although some patients may have had recent outpatient testing. In the event that testing is
not performed early after an ACS, values obtained up to four days after the event may represent baseline
values. (See "Measurement of serum lipids and lipoproteins", section on 'After an ACS'.)

Evaluation of the response to statin therapy after an acute coronary syndrome should be deferred for two
months, since acute phase responses and perhaps other factors can transiently lower LDL-cholesterol by
40 to 50 percent and thus, in some patients, cause spuriously normal-appearing levels following an acute
coronary syndrome. However, the magnitude of this effect, at least soon after hospitalization, appears to
be less with current therapies that limit the degree of myocardial injury, such as percutaneous coronary
intervention or fibrinolytic therapy [25]. (See "Measurement of serum lipids and lipoproteins", section on
'After an ACS' and "Cholesterol lowering after an acute coronary syndrome".)
The long-term LDL-cholesterol goal is discussed separately. (See "Intensity of lipid lowering therapy in
secondary prevention of coronary heart disease".)
Antithrombotic therapy
Antiplatelet therapy In the absence of an absolute contraindication, antiplatelet therapy
with aspirin and a platelet P2Y12 receptor blocker is indicated in all patients with a non-ST elevation
ACS [1,2]. (See "Antiplatelet agents in acute non-ST elevation acute coronary syndromes".)
Anticoagulation For all patients with non-ST elevation ACS, we recommend anticoagulant therapy as
soon as possible after the diagnosis. (See "Anticoagulant therapy in non-ST elevation acute coronary
syndromes".)
Importance of dosing Excessive dosing of antithrombotic and antiplatelet agents is common and
associated with an increase in bleeding risk. This issue is discussed separately. (See "Anticoagulant
therapy in non-ST elevation acute coronary syndromes", section on 'Anticoagulant regimens'.)
Potassium and magnesium Although there are no clinical trials documenting the benefits of
electrolyte replacement in acute MI, the ACC/AHA guidelines recommend maintaining the serum
potassium concentration above 4.0 meq/L and a serum magnesium concentration above 2.0 meq/L (2.4
mg/dL or 1 mmol/L) [26,27]. Much of the evidence for this recommendation was derived from studies
before the routine use of beta blocker and the use of reperfusion in many patients. (See "Clinical features
and treatment of ventricular arrhythmias during acute myocardial infarction", section on 'Ventricular
fibrillation'.)
A 2012 retrospective cohort study found that for patients with acute MI the lowest mortality was observed
in those with post-admission serum potassium values between 3.5 and <4.5 meq/L [28]. (See "Risk
stratification for cardiac events after acute ST elevation myocardial infarction", section on 'Serum
potassium'.)
We suggest that the serum potassium fall within the range of 3.5 to 4.5 meq/L. Some of our reviewers
prefer a tighter range of 4.0 to 4.5 meq/L. It may be difficult to lower the potassium below 4.5 meq/L in
some patients, such as those with chronic kidney disease.
Non-steroidal antiinflammatory drugs Nonsteroidal antiinflammatory drugs (except aspirin) should
be discontinued immediately due to an increased risk of cardiovascular events associated with their use.
(See "Nonselective NSAIDs: Adverse cardiovascular effects".)
Intravenous glucose-insulin-potassium We do not recommend the use of intravenous glucoseinsulin-potassium (GIK) to improve outcomes in patients with suspected or diagnosed acute MI. Much of
the available evidence comes from studies of patients with ST-elevation MI. The discussion of the
potential use of GIK in these patients is found elsewhere. (See "Overview of the acute management of ST
elevation myocardial infarction", section on 'Intravenous glucose-insulin-potassium'.)

The IMMEDIATE trial randomly assigned 871 patients with suspected acute coronary syndromes
(approximately 60 percent without ST-elevation on the presenting electrocardiogram) to intravenous GIK
or identical-appearing 5 percent glucose placebo, which was administered by paramedics in the out-ofhospital setting and continued for 12 hours [29]. There was no difference in the rate of progression to MI
(as measured by biomarkers and ECG evidence) at 24 hours or the rate of death at 30 days among
patients who received GIK compared to those who received placebo (48.7 versus 52.6 percent; odds ratio
0.88, 95% CI 0.66-1.13 and 4.4 versus 6.1 percent; odds ratio 0.72, 95% CI 0.40-1.29, respectively).
ARRHYTHMIA MANAGEMENT Both atrial and ventricular arrhythmias can be seen during and after
the acute phase of an NSTEMI. These include atrial fibrillation or flutter, which can cause symptomatic
hypoperfusion due to a rapid rate, and life-threatening ventricular tachycardia or ventricular fibrillation.
(See "Supraventricular arrhythmias after myocardial infarction" and "Clinical features and treatment of
ventricular arrhythmias during acute myocardial infarction".)
Prophylactic intravenous or intramuscular lidocaine to prevent VT/VF in the acute MI patient
is not recommended. Recommended prophylactic measures include early administration of a beta
blocker and treatment of hypokalemia and hypomagnesemia. Treatment of ventricular tachyarrhythmias in
the setting of acute MI is discussed separately. (See "Clinical features and treatment of ventricular
arrhythmias during acute myocardial infarction".)
EARLY RISK STRATIFICATION Early risk stratification in patients with ACS is essential to identify
those patients at highest risk for further cardiac events who may benefit from a more aggressive
therapeutic approach [1,30,31]. Clinical trials have identified a number of factors predicting high risk and a
benefit from an early invasive strategy [32-36]. These include the presence and extent of ST segment
depression, elevated cardiac biomarkers, evidence of hemodynamic instability, and persistent chest pain
despite appropriate medical therapy. These variables have been used to create risk scores such as TIMI,
GRACE, and PURSUIT. (See "Risk stratification after unstable angina or non-ST elevation myocardial
infarction" and "Trials of conservative versus early invasive therapy in unstable angina and non-ST
elevation myocardial infarction".)
It should be noted, however, that individual factors in the seven-point TIMI risk score may carry more risk
than others, or be more specific for acute coronary syndrome than others. As an example, serum troponin
elevation and ST segment depression individually are markers of high risk, regardless of the other TIMI
risk factors.
TIMI risk score Analysis of data from the TIMI 11B and ESSENCE trials found that seven variables at
presentation were independently predictive of outcome in patients with unstable angina or an NSTEMI; a
value of one was assigned when a factor was present and 0 when it was absent (calculator 1) [37]:

Age 65 years

Presence of at least three risk factors for CHD (hypertension, diabetes, dyslipidemia, smoking, or
positive family history of early MI)

Prior coronary stenosis of 50 percent

Presence of ST segment deviation on admission ECG

At least two anginal episodes in prior 24 hours

Elevated serum cardiac biomarkers

Use of aspirin in prior seven days (which is probably a marker for more severe coronary disease)
[38]

Patients are considered to be at low risk with a score of 0 to 2; intermediate risk with a score of 3 to 4;
and high risk with a score of 5 to 7 (figure 1).
EARLY REPERFUSION AND REVASCULARIZATION
Avoidance of fibrinolysis Prospective trials have demonstrated that fibrinolytic therapy is not
beneficial in patients with a non-ST elevation ACS [1,32,39]. The ACC/AHA and ACCP
recommend against the routine use of fibrinolytic agents in patients with a non-ST elevation ACS [40,41].
(See "Fibrinolytic (thrombolytic) agents in unstable angina and acute non-ST elevation myocardial
infarction".)
Immediate angiography and revascularization Patients who have a non-ST elevation ACS and one
or more of the following characteristics are at extremely high risk of an adverse cardiovascular event in
the short term:

Hemodynamic instability or cardiogenic shock

Severe left ventricular dysfunction or heart failure

Recurrent or persistent rest angina despite intensive medical therapy

New or worsening mitral regurgitation or new ventricular septal defect

Sustained ventricular arrhythmias

We recommend that patients with any of these five characteristics be referred for immediate coronary
arteriography and revascularization.
For those without one of the above extremely high risk characteristics, randomized trials have shown
benefit of an early invasive approach in high-risk ACS. While the optimal timing is uncertain, the majority
of patients undergo coronary revascularization early (ie, within 24 hours). This early timing was shown to
be of clear benefit in high-risk patients in the TIMACS trial and subgroup analyses of major trials support
this approach in elderly patients as well as younger patients [11]. (See "Coronary arteriography and
revascularization for unstable angina or non-ST elevation acute myocardial infarction", section on 'Timing
of early intervention'.)
A widely used predictive model used to guide invasive versus conservative strategy is the TIMI risk
score, which is based upon seven variables available at presentation [37]. Patients with high-risk TIMI
scores of five to seven, as well as intermediate-risk TIMI scores of three to four, benefited from early
invasive strategy in the TACTICS-TIMI 18 trial. (See 'Early risk stratification' above and "Coronary
arteriography and revascularization for unstable angina or non-ST elevation acute myocardial infarction",
section on 'TIMI risk score'.)
High risk criteria have also been defined by the 2007 ACC/AHA guidelines on unstable angina and nonST elevation MI and the 2005 European Society of Cardiology guidelines as cardiac biomarker elevations,

ST segment depression, recurrent angina, hemodynamic instability, sustained VT/VF, prior PCI within the
prior six months or CABG, and diabetes [1,42]. (See "Coronary arteriography and revascularization for
unstable angina or non-ST elevation acute myocardial infarction".)
The choice of revascularization procedure after angiography depends upon the location and extent of
disease. Among patients with an appropriate lesion, PCI is most often performed, but coronary artery
bypass grafting (CABG) is usually preferred for the treatment of patients with left main or left main
equivalent disease, or three or two vessel disease involving the left anterior descending artery with left
ventricular dysfunction or treated diabetes [43]. (See "Coronary arteriography and revascularization for
unstable angina or non-ST elevation acute myocardial infarction", section on 'PCI versus CABG'.)
MI with normal coronary arteries In clinical trials, 9 to 14 percent of patients with a non-ST elevation
ACS who undergo early angiography have no significant coronary stenosis [33,34,44-46]. Possible
mechanisms include rapid clot lysis, vasospasm, myocarditis, and coronary microvascular disease. Such
patients have a much better short-term prognosis than those with a culprit lesion [45,46].
(See "Classification of unstable angina and non-ST elevation myocardial infarction", section on 'Absence
of significant coronary disease' and "Variant angina" and "Evaluation and management of the
cardiovascular complications of cocaine abuse" and "Cardiac syndrome X: Angina pectoris with normal
coronary arteries", section on 'Acute coronary syndrome' and "Clinical manifestations and diagnosis of
myocarditis in adults", section on 'Electrocardiogram'.)
SUMMARY Unstable angina and acute non-ST elevation myocardial infarction (NSTEMI) are medical
emergencies requiring the simultaneous application of multiple therapies. After the emergent period, other
therapies may need to be started. (See "Overview of the non-acute management of unstable angina and
non-ST elevation myocardial infarction".)
Women and men should be managed similarly. Other patients, such as the elderly and those with either
cocaine associated MI, are managed somewhat differently. (See'General principles' above.)
The initial assessment and therapy of unstable angina and NSTEMI is summarized in table form (table 1)