Acute Coronary Syndromes

Acute Coronary Syndromes

Jean Marie Blue Verrier

Michaelene Hargrove Deelstra

In 2005, there were an estimated 16 million people in the United States with coronary heart disease (CHD), translating to approximately 1 in every 15 Americans. Of these cases, 1.2 million were new or recurrent CHD. There were 451,300 CHD-related deaths in 2004.1

Acute coronary syndromes (ACS) have evolved over the last 10 years into an operational term referring to a constellation of clinical symptoms that equate to myocardial ischemia. Ischemic heart disease is one type of CHD. ACS encompasses ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA). Identification of ACS at the earliest point in the health care continuum allows paramedics to initiate immediate cardiac medications and route patients to the most appropriate facilities for care. The shortest time to reperfusion is the most desirable goal of treatment and management of the patient population with ACS.2,3

UA/NSTEMI constitutes a clinical syndrome that is a subset of ACS. UA/NSTEMI is usually, but not always, caused by atherosclerotic coronary artery disease (CAD, a type of CHD) and is associated with an increased risk of cardiac mortality.4 CAD is also associated with an increased incidence of myocardial infarction (MI). As a subset of ACS, UA/NSTEMI is defined by electrocardiographic ST-segment depression or prominent T-wave inversion. Biomarkers of myocardial necrosis, such as troponin, may or may not be present. No ST-segment elevation is present on electrocardiogram (ECG). The patient typically has chest discomfort or an anginal equivalent.4

Variant (Prinzmetal’s) angina is an unusual form of UA that occurs spontaneously and frequently is not related to exertion. The chest discomfort tends to be prolonged and severe. It is caused by spasm of the epicardial coronary artery/arteries and classically is characterized by transient ST-segment elevation that resolves with nitroglycerin (NTG) use.

Patients presenting with STEMI have a high likelihood of coronary thrombus causing a complete occlusion of the artery. Angiographic evidence of coronary thrombus formation is seen in more than 90% of patients with STEMI but in only 35% to 75% of patients presenting with UA/NSTEMI. There is ST-segment elevation evident on ECG. Biomarkers of myocardial necrosis such as troponin are typically elevated. The patient generally has chest discomfort or an anginal equivalent.2

In the last several years, there has been an unprecedented focus on quantifying and improving health care delivery. The American College of Cardiology (ACC) and the American Heart Association (AHA) jointly have developed a long-term strategy to improve clinical care. The initial phase created practice guidelines that synthesized available evidence to guide care. The second phase developed performance measures to assess and improve the quality of cardiovascular care. Table 22-1 presents the ACC/AHA STEMI/NSTEMI performance measurement set developed in January 2006.5 The measures include aspirin therapy at arrival and at discharge; β-blocker therapy at arrival and at discharge; low-density lipoprotein cholesterol (LDL-C) assessment; lipidlowering therapy at discharge; angiotensin-converting enzyme inhibitor (ACEI) and/or angiotensin II receptor blocker (ARB) therapy for left ventricular (LV) systolic dysfunction; time-to-fibrinolytic therapy; time-to-percutaneous coronary intervention (PCI); reperfusion therapy; and adult smoking cessation advice/counseling.5 Pathogenesis of ACS is presented in Chapter 5. PCI is presented in Chapter 23. ACS risk factors are presented in Chapter 32. For a complete presentation of the care of patients with STEMI and UA/NSTEMI, refer to the original sources for the ACC/AHA STEMI2,3 and NSTEMI Guidelines,4 which simply are abstracted here for purposes of this chapter.


Morbidity and mortality from ACS can be reduced significantly if symptoms are recognized early. The symptoms of UA/NSTEMI and STEMI include midsternal or substernal compression or crushing chest discomfort. The patient may describe it as a cramping, burning, or an aching sensation in the midsternal area. The discomfort may also be described as pressure, tightness, or heaviness in the chest. Unexplained indigestion or belching with or without epigastric pain is also a common subjective complaint. The pain may radiate to the neck, jaw, shoulders, back, or one or both arms. Commonly there is associated dyspnea, nausea and/or vomiting, and diaphoresis. Women more often than men present with atypical chest pain. Patients with diabetes also may present atypically due to diabetes-associated autonomic dysfunction.
Older adults can present with stroke, syncope, a change in mental status, and/or generalized weakness.


Performance Measure


Patient Education



Monitoring of Disease Status*


Aspirin at arrival


Aspirin prescribed at discharge


β-Blocker at arrival


β-Blocker prescribed at discharge


LDL-C assessment


Lipid-lowering therapy at discharge




Time to fibrinolytic therapy


Time to PCI


Reperfusion therapy


Adult smoking cessation advice/counseling

* Although no current measures exist for these dimensions of care for the inpatient setting, future measure development efforts will examine how to address this gap in the measurement set.

LVSD, left ventricular systolic dysfunction.

Anderson, J.L., Bennett, S. J., Brooks, N. H., et al. (2006). ACC/AHA clinical performance measures for adults with ST-elevation and non-ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association task force on performance measures. JACC, 47, 236-65.

There are three common principal presentations of UA.4 Resting angina pectoris, as the name implies, occurs during a period of nonexertion. Exertion in this setting can be physical exertion with routine activities, exercise, emotional exertion, and/or stress. The emotional exertion or stress can be related to any strong emotional reaction, such as excitation over a ball game or an event that provokes excitation, anxiety, or anger. The second principal presentation of UA is classified as new-onset angina that has its onset in less than 2 months. The third presentation is crescendo or increasing angina.6 The increase can reflect intensity, duration, and/or frequency of anginal symptoms. Compared with UA, NSTEMI generally presents as prolonged, more intense resting angina or an anginal equivalent, such as shortness of breath, or jaw or arm pain.

Variant angina usually does not progress to MI. Uncommonly, prolonged vasospasm can result in MI, atrioventricular block, ventricular tachycardia, or sudden death.4 Attacks can be precipitated by emotional stress, hyperventilation, exercise, or exposure to cold. The anginal attacks tend to occur more in the morning. Patients with variant angina tend to be younger with fewer coronary risk factors. This type of angina is usually responsive to NTG, long-acting nitrates, and calcium antagonists, all of which are first-line therapies.4 Smokers should stop smoking. Prognosis with medical therapy is usually good, particularly in the presence of a normal coronary angiogram. If CAD is present on angiogram, then the prognosis is not as good.

Refer to Chapter 10 for a complete discussion of the cardiovascular history and physical examination, and to Chapters 11 and 15 for details of cardiac biomarker and 12-lead ECG interpretation, respectively.


The ACC/AHA 2007 recommendations for initial evaluation and management follow.4 Table 22-2 illustrates the classification and certainty of treatment effect for these recommendations.

  • Patients with symptoms suggestive of ACS should be instructed to call 911 and should be transported to the emergency department by ambulance rather than by private transport. (Class I, level of evidence: B)

  • The prehospital emergency medical providers should administer at this time aspirin 162 to 325 mg to the patient suspected of ACS unless contraindicated or if already taken by the patient. More rapid buccal absorption occurs with non-enteric-coated formulations and is recommended. (Class I, level of evidence: C)

  • Health care providers performing initial assessment of a patient suspected of ACS that has had NTG prescribed should instruct the patient not to take more than one dose of NTG sublingually in response to chest discomfort. If chest discomfort is unimproved or is worsening 5 minutes after dosing, it is recommended that the patient or family member call 911 immediately to access emergency medical services (EMS). In patients with chronic stable angina whose symptoms have improved after one NTG, it is appropriate to instruct the patient to repeat NTG every 5 minutes for a maximum of three doses. If symptoms do not resolve completely after three doses, 911 should be called for evaluation and treatment of symptoms. (Class I, level of evidence: C)

  • Patients with suspected ACS who have chest discomfort or other ischemic symptoms at rest for greater than 20 minutes, hemodynamic instability, or recent presyncope/syncope should be referred immediately to an emergency department for further evaluation. Patients experiencing less severe symptoms and who have none of the high-risk features described in the next section can be seen initially in an outpatient facility able to provide an acute evaluation. This recommendation would include patients who responded to an NTG dose. (Class I, level of evidence: C)

  • If the EMS providers have the capability, a 12-lead ECG should be performed in the field and transmitted to an emergency physician. The ECG assists in triage decisions, allowing transport to the most appropriate emergency department. ECGs with validated computer-generated interpretation are recommended in this setting. (Class IIa, level of evidence: B)


Size of Treatment Effect



Class I
Benefit >>> Risk

Class IIa
Benefit >> Risk Additional studies with focused objectives needed

Class IIb
BenefitRisk Additional studies with broad objectives needed; Additional registry data would be helpful

Class III
RiskBenefit No additional studies needed

Procedure/Treatment SHOULD be performed/administered

IT IS REASONABLE to perform procedure/administer treatment

Procedure/Treatment MAY BE CONSIDERED

Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL, AND IT MAY BE HARMFUL

Level A

  • Recommendation that procedure or treatment is useful/effective

  • Sufficient evidence from multiple randomized trials or meta-analyses

  • Recommendation in favor of treatment or procedure being useful/effective

  • Some conflicting evidence from multiple randomized trials or meta-analyses

  • Recommendation’s usefulness/efficacy less well established

  • Greater conflicting evidence from multiple randomized trials or meta-analyses

  • Recommendation that procedure or treatment is not useful/effective and may be harmful

  • Sufficient evidence from multiple randomized trials or meta-analyses

Multiple (3-5) population risk strata evaluated*

General consistency of direction and magnitude of effect

Level B

  • Recommendation that procedure or treatment is useful/effective

  • Limited evidence from single randomized trials or non-randomized studies

  • Recommendation in favor of treatment or procedure being useful/effective

  • Some conflicting evidence from single randomized trial or non-randomized studies

  • Recommendation’s usefulness/efficacy less well established

  • Greater conflicting evidence from single randomized trial or non-randomized studies

  • Recommendation that procedure or treatment is not useful/effective and may be harmful

  • Limited evidence from single randomized trial or non-randomized studies

Limited (2-3) population risk strata evaluated*

Level C

  • Recommendation that procedure or treatment is useful/effective

  • Only expert opinion, case studies, or standard-of-care

  • Recommendation in favor of treatment or procedure being useful/effective

  • Only diverging expert opinion, case studies, or standard-of-care

  • Recommendation’s usefulness/efficacy less well established

  • Only diverging expert opinion, case studies, or standard-of-care

  • Recommendation that procedure or treatment is not useful/effective and may be harmful

  • Only expert opinion, case studies, or standard-of-care

Very limited (1-2) population risk strata evaluated*

Suggested phrases for writing recommendations

Is recommended
Is indicated
Is useful/effective/beneficial

Is reasonable
Can be useful/effective/beneficial
Is probably recommended or indicated

May/might be considered
May/might be reasonable
Usefulness/effectiveness is unknown/unclear/uncertain or not well established

Is not recommended
Is not indicated
Should not
Is not useful/effective/beneficial
May be harmful

In 2003, the ACC/AHA Task Force on Practice Guidelines developed a list of suggested phrases to use when writing recommendations. All guideline recommendations have been written in full sentences that express a complete thought, such that a recommendation, even if separated and presented apart from the rest of the document (including headings above sets of recommendations), would still convey the full intent of the recommendation. It is hoped that this will increase readers’ comprehension of the guidelines and will allow queries at the individual recommendation level.

* Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be very clear clinical consensus that a particular test or therapy is useful or effective.

Anderson, L. J, Bennett, S. J., Brooks, N. H., et al. (2006). ACC/AHA clinical performance measures for adults with ST-elevation and non-ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association task force on performance measures. JACC, 47, 236-65.

Early Risk Stratification

An estimation of risk is useful in selection of the initial medical and interventional therapies. Generally, risk is highest at the time of presentation and declines subsequently but remains elevated even beyond the acute phase. In patients with symptoms suggestive of ACS, the initial medical history, physical examination, ECG, and assessment of renal function and cardiac biomarker can be integrated into an estimation of the risk of mortality or a nonfatal cardiac event.

The five most important factors on the initial history are the nature of the anginal symptoms, a prior history of CAD, sex, age, and the number of risk factors present. In patients without preexisting clinical CHD, older age is the most important factor.4

A history of MI increases the risk of obstructive and multivessel CAD. Traditional risk factors are only weakly predictive of the likelihood of acute ischemia, and they are less important than symptoms, ECG findings, and cardiac biomarkers.7 Diabetes mellitus and extracardiac disease are major risk factors for poor outcomes in patients with ACS.4 The ECG is central to the diagnostic and triage pathway for ACS. Figure 22-1 illustrates practice guidelines recommended for ACS and demonstrates the pivotal role the 12-lead ECG plays in treatment course selection. Transient ST-segment changes greater than or equal to 0.05 mV or 0.5 mm that develop during the time the patient is symptomatic at rest is strongly suggestive of myocardial ischemia due to severe CAD.

Patients who present with ST-segment depression could have either UA or NSTEMI. The distinction is made by the later detection of biomarkers of myocardial necrosis. Inverted T waves, particularly if greater than or equal to 2 mm, can also be indicative of UA/NSTEMI. Q waves are suggestive of prior MI and indicate high likelihood of CAD. A normal ECG does not completely exclude ACS; 1% to 6% of patients with documented NSTEMI and 4% of patients with documented UA will have a normal ECG. Serial ECGs increase diagnostic sensitivity and are recommended because ST-segment elevation on the 12-lead ECG is the principal criterion for reperfusion therapy. Figure 22-2 shows anterior ST-segment elevation indicative of acute anterior STEMI.

Figure 22-1 Acute Coronary Syndromes. The top half of the figure illustrates the chronology of the interface between the patient and the clinician through the progression of plaque formation, onset, and complications of UA/NSTEMI, along with relevant management considerations at each stage. The longitudinal section of an artery depicts the “timeline” of atherogenesis from (1) a normal artery to (2) lesion initiation and accumulation of extracellular lipid in the intima, to (3) the evolution to the fibrofatty stage, to (4) lesion progression with procoagulant expression and weakening of the fibrous cap. An ACS develops when the vulnerable or high-risk plaque undergoes disruption of the fibrous cap (5); disruption of the plaque is the stimulus for thrombogenesis. Thrombus resorption may be followed by collagen accumulation and smooth muscle cell growth (6). After disruption of a vulnerable or high-risk plaque, patients experience ischemic discomfort that results from a reduction of flow through the affected epicardial coronary artery. The flow reduction may be caused by a completely occlusive thrombus (bottom half, right side) or subtotally occlusive thrombus (bottom half, left side). Patients with ischemic discomfort may present with or without ST-segment elevation on the ECG. Among patients with ST-segment elevation, most (thick red arrow in bottom panel) ultimately develop a Q-wave MI (QwMI), although a few (thin red arrow) develop a non-Q-wave MI (NQMI). Patients who present without ST-segment elevation are suffering from either UA or a non-ST-segment elevation MI (NSTEMI) (thick white arrows), a distinction that is ultimately made on the basis of the presence or absence of a serum cardiac marker such as CK-MB or a cardiac troponin detected in the blood. Most patients presenting with NSTEMI ultimately develop an NQMI on the ECG; a few may develop a QwMI. The spectrum of clinical presentations ranging from UA through NSTEMI and STEMI is referred to as the ACSs. This UA/NSTEMI guideline, as diagrammed in the upper panel, includes sections on initial management before UA/NSTEMI, at the onset of UA/NSTEMI, and during the hospital phase. Secondary prevention and plans for long-term management begin early during the hospital phase of treatment. Dx, diagnosis; NQMI, non-Q-wave MI; QwMI, Q-wave MI. (From Anderson, J. L., Adams, C. D., Antman, E. M., et al. (2007). ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Journal of American College of Cardiology, 50(7), e1-e157.)

Figure 22-2 Chest leads from a patient with acute anterior wall infarction. (A) In the earliest phase of the infarction, tall, positive (hyperacute) T waves are seen in leads V2 to V5. (B) Several hours later, marked ST depression is seen in the same leads and abnormal Q waves are seen in leads V1 and V2. (From Goldberger, A. L. [1999]. Clinical electrocardiography: A simplified approach [6th ed.]. St. Louis, MO: C.V. Mosby.)

Potential precipitating factors of myocardial ischemia, such as uncontrolled hypertension, thyrotoxicosis, or gastrointestinal bleeding, are identified on physical examination. Identification of any comorbid conditions, such as pulmonary disease or malignancy, is critical because both therapeutic risk and clinical decision making could be altered. Immediate evaluation is important to rule out alternative diagnoses of noncardiac chest pain, including aortic dissection (suggestive with findings of unequal pulses or a loud new aortic murmur), acute pericarditis (presents with pleuritic chest pain and/or the presence of a friction rub), pulmonary embolism, tension pneumothorax, myocarditis, perforating peptic ulcer, and esophageal rupture.2 The physical examination will also give indications as to the hemodynamic effect of the myocardial ischemia, such as hypotension and organ hypoperfusion seen in cardiogenic shock—a medical emergency. Practice guidelines for patient management in the early risk stratification phase follow4:

  • A rapid clinical determination of risk for obstructive CAD that focuses on history, physical findings, ECG findings, and cardiac biomarker integration should be made in all patients experiencing chest discomfort suggestive of ACS. (Class I, level of evidence: C)

  • A 12-lead ECG should be performed and evaluated by an emergency department physician of any patient with chest discomfort or anginal equivalent within 10 minutes of arrival to the facility. (Class I, level of evidence: C)

  • If the initial ECG demonstrates no evidence of ischemia but the patient remains symptomatic, serial ECGs at 15- to 30-minute intervals should be performed to detect the development of ST-segment elevation or depression. (Class I, level of evidence: B)

  • Cardiac biomarkers should be measured in all patients who present with chest discomfort indicative of ACS. Cardiac-specific troponin is the preferred biomarker and should be measured in all patients presenting with chest discomfort suggestive of ACS. Patients with negative cardiac biomarkers within 6 hours from the onset of symptoms should have biomarkers remeasured in 8 to 12 hours after the onset of symptoms. (Class I, level of evidence: B)

  • For patients with suspected ACS, troponin-I is the laboratory marker of choice as it is found exclusively in the myocardium. Because of its specificity and sensitivity for detecting myocardial ischemia, troponin-I has become the preferred method of measurement. Other markers of pathophysiologic mechanisms implicated in ACS are under investigation, including markers of coagulation, platelet activation, inflammation, and heart failure. B-type natriuretic peptide, used to indicate the presence of heart failure, has been shown to provide incremental prognostic value in patient cohorts with STEMI and UA/NSTEMI.8, 9, 10

  • Various forms of imaging are often used to evaluate patients with symptoms that are suggestive of ACS. Bedside echocardiography is useful for diagnosis and risk stratification of patients with ACS in the emergency department.2 A portable chest radiograph is a Class I recommendation by the ACC guidelines in STEMI. It should not however delay reperfusion strategies.

Immediate Patient Management

Following are the ACC/AHA guidelines for immediate patient management of patients with ACS.2,4 An in-depth discussion of the medications used in ACS is presented later in this chapter. Figure 22-3 illustrates the ACC/AHA algorithm for the management of ACS. Figure 22-4 illustrates AHA’s Advanced Cardiac Life Support algorithm for chest discomfort suggestive of ischemia.

  • The history, physical examination, 12-lead ECG, and initial cardiac biomarkers should be utilized to categorize the chest discomfort into one of four groups: noncardiac diagnosis, chronic stable angina, possible ACS, and definite ACS. (Class I, level of evidence: C)

  • Patients with possible ACS but whose initial 12-lead ECG and cardiac biomarker levels are normal should be observed with ongoing cardiac monitoring, serial ECGs, and repeat biomarker measurement. (Class I, level of evidence: B)

  • In patients with symptoms suggestive of ACS in whom ischemic heart disease is present or suspected, but the follow-up 12-lead ECG and cardiac biomarkers measurements are normal, a stress test (exercise or pharmacologic) to provoke ischemia should be performed in the emergency department within 72 hours of discharge. (Class I, level of evidence: C)

  • In the patient population recommended for outpatient stress testing, precautionary appropriate pharmacotherapy should be prescribed including aspirin, β-blockers, and/or sublingual NTG. If the patient is discharged from the emergency
    department for outpatient stress testing he/she should receive instruction on activity, medication, and follow-up care with an appropriate health care provider. Patients with definite ACS and ongoing ischemia, positive cardiac biomarkers, new ST-segment deviations, new deep T-wave inversions, hemodynamic abnormalities, or a positive stress test in the emergency department should be admitted to the hospital for further treatment and possible invasive management. Admission to the critical care unit is advised for those patients with active, ongoing ischemia and hemodynamic or electrical instability. (Class I, level of evidence: C)

  • Any patient presenting with STEMI, new or presumed new left bundle-branch block (LBBB) should be evaluated for immediate reperfusion therapy (Class I, level of evidence: A)

  • At this point, bed rest should be maintained to decrease activity and myocardial oxygen consumption. Supplemental oxygen should be administered to patients with ACS particularly if any degree of respiratory insufficiency or hypoxia is present. Oral or intravenous (IV) β-blocker therapy should be administered to those patients with STEMI without a contraindication, irrespective of concomitant fibrinolytic therapy or performance of primary PCI (Class I, level of evidence: A)

  • In the absence of contraindications, morphine sulfate is the analgesic of choice for the management of pain associated with STEMI (Class I, level of evidence: C). Analysis of retrospective data has raised a question as to the potentially adverse effects of morphine in patients with UA/NSTEMI.1 As a result morphine use in that patient population has been reduced to a Class IIa recommendation.

  • IV NTG is recommended for ongoing chest discomfort unrelieved by sublingual NTG dosing, control of hypertension, or management of pulmonary congestion (Class I, level of evidence: C)

Figure 22-3 Algorithm for the evaluation and management of patients suspected of having ACS. (Reproduced with permission of the American Heart Association, 2006.)


Coronary revascularization strategies include PCI, pharmacologic reperfusion, and coronary artery bypass graft (CABG) surgery. Coronary revascularization is performed to improve prognosis, relieve symptoms, prevent ischemic complications, and improve functional capacity. CABG is primarily indicated for patients with left main CAD, three-vessel disease with LV dysfunction, or for those patients for whom PCI is not optimal. Table 22-3 presents the ACC/AHA guidelines for selecting a reperfusion strategy. A full discussion of indications for PCI and CABG can be found in Chapters 23 and 25, respectively.

Figure 22-4 ACSs algorithm for chest discomfort suggestive of ischemia. (Reproduced with permission of the American Heart Association, 2006.)


Step 1: Assess time and risk

  • Time since onset of symptoms

  • Risk of STEMI

  • Risk of fibrinolysis

  • Time required for transport to a skilled PCI laboratory

Step 2: Determine if fibrinolysis or invasive strategy is preferred

If presentation is less than 3 hours and there is no delay to an invasive strategy, there is no preference for either strategy

Fibrinolysis is generally preferred if:

  • Early presentation (3 hours from symptom onset and delay to invasive strategy) (see below)

  • Invasive strategy is not an option
    Catheterization laboratory occupied/not available
    Vascular access difficulties
    Lack of access to a skilled PCI laboratory

  • Delay to invasive strategy
    Prolonged treatment

An invasive strategy is generally preferred if:

  • Skilled PCI laboratory available with surgical backup
    Medical contact-to-balloon or door-to-balloon time is <90 minutes
    (Door-to-balloon)-(door-to-needle) time is <1 hour

  • High risk from STEMI
    Cardiogenic shock
    Killip class is ≥ 3

  • Contraindications to fibrinolysis including increased risk of bleeding and intracranial hemorrhage

(Door-to-balloon)-(door-to-needle) is >1 hour
Medical contact-to-balloon or door-to-balloon is >90 minutes

  • Late presentation
    Symptom onset was >3 hours ago

  • Diagnosis of STEMI is in doubt

From Boden, W. E., Eagle, K., & Granger, C. B. (2007). Reperfusion strategies in acute ST-segment elevation myocardial infarction: A comprehensive review of contemporary management options. Journal of American College of Cardiology, 50(10), 917-929.

From Antman, J. L., Anbe, D. T., Armstrong, P. W., et al. (2004). ACC/AHA Guidelines for the Management of Patients with ST-elevation Myocardial Infarction: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). Journal of American College of Cardiology, 44, 671-719.

Optimizing Door-to-Balloon or Medical Contact-to-Needle Time

The current ACC/AHA STEMI Guidelines2 are based on clinical data that support the time-dependent nature of myocardial necrosis. A delay in time-to-treatment (PCI or fibrinolysis) translates directly to increased mortality.11 To improve the quality of STEMI care, there has been increased focus on strategies that both increase access to primary PCI and improve time-to-treatment with particular emphasis on door-to-balloon time. Strong clinical evidence supports the early-open-artery hypothesis12 of the important relation between achieving prompt antegrade blood flow of the infarct artery and improved clinical outcomes for both fibrinolysis13, 14, 15 and primary PCI.16, 17, 18, 19, 20 Door-to-balloon time is one of the performance measures regarding quality of care for STEMI.2,3 The goal of EMS is to facilitate rapid recognition and treatment of patients with STEMI and implement quickly the most appropriate reperfusion strategy. Thus, the ACC/AHA Guidelines2 recommend that all hospitals have established multidisciplinary teams to develop guideline-based, institution-specific written protocols for triaging and managing patients who present with symptoms suggestive of myocardial ischemia. Specific goals are to implement door-to-needle time (or medical contact-to-needle time) of 30 minutes for initiation of fibrinolytic therapy, or door-to-balloon time (or medical contact-to-balloon time) within 90 minutes for primary PCI. STEMI patients presenting to a facility without the capability for expert, prompt intervention with primary PCI within 90 minutes of first medical contact should undergo fibrinolysis within 30 minutes unless contraindicated. (Class I, level of evidence: B)3

The late-open-artery hypothesis proposed that late reestablishment of antegrade flow would improve LV function, enhance electrical stability, and encourage collateral vessel growth.3 However, in patients with persistent total occlusion of the infarct-related artery 3 to 28 days after the acute event, there was no delayed benefit of PCI over optimal medical therapy alone (aspirin, β-blockers, ACEI, and statins),21 and therefore no support for PCI outside the therapeutic window in an asymptomatic patient following STEMI.3,12

Pharmacological Reperfusion/Fibrinolytic Therapy

The development of pharmacological fibrinolytic agents to restore coronary blood flow was based on the science and clinical research that identified the pathogenesis of STEMI. DeWood et al. who performed coronary angiography in patients with STEMI found that 85% had thrombotic coronary artery occlusion in the early hours of transmural MI.22 Rentrop et al. demonstrated acute reperfusion of occluded infarct arteries with streptokinase.23 The Western Washington randomized trial of intracoronary streptokinase24 and the Netherlands Interuniversity Cardiology Institute trial25 stimulated the intense interest in fibrinolytic therapy. Fibrinolytic therapy has been developed over the last two decades and shown to restore infarct artery patency, reduce infarct size, preserve LV function, and decrease mortality in patients with STEMI.26 Patients with STEMI who receive fibrinolytic therapy have better short- and long-term survival when treatment is instituted rapidly, with early reestablishment of flow within 2 to 3 hours after onset of symptoms. Little benefit is seen with fibrinolytic therapy after 12 hours, which is theorized to be related to thrombus organization within the coronary artery over time and loss of an opportunity for restoration of blood flow and myocardial salvage.27







1.5 million units over 30 to 60 minutes

Up to 100 mg in 90 minutes (based on weight)*

10 U × 2 each over 2 minutes

30 to 50 mg based on weight

Bolus administration










Allergic reactions (hypotension most common)





Systemic fibrinogen depletion





90-minute patency rates, approximate %





TIMI grade 3 flow, %





Cost per dose (US$) in 2004




$2,833 for 50 mg

* Bolus 15 mg, infusion 0.75 mg/kg times 30 minutes (maximum 50 mg), then 0.5 mg/kg not to exceed 35 mg over the next 60 minutes to an overall maximum of 100 mg.

Thirty milligrams for weight less than 60 kg; 35 mg for 60 to 69 kg; 40 mg for 70 to 79 kg; 45 mg for 80 to 89 kg; 50 mg for 90 kg or more.

Antman, J.L., Anbe D.T., Armstrong P.W., et al. (2004). ACC/AHA Guidelines for the Management of Patients with ST-elevation Myocardial Infarction: A report of the American College of Cardiology/American Heart Association task force on Practice Guidelines (writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). JACC, e3-e170.

Indications for Fibrinolysis

In the absence of contraindications, fibrinolytic therapy should be administered to STEMI patients who have onset of symptoms within the previous 12 hours and (1) ST-segment elevation greater than 0.1 mV in at least two contiguous precordial leads or at least two adjacent limb leads or (2) new or presumably new LBBB (Class I, level of evidence: A).2 The failure of IV fibrinolytic therapy to improve clinical outcomes in the absence of STEMI or LBBB was demonstrated in the Thrombolysis in Myocardial Ischemia 111B (TIMI 111B),28 International Study of Infarct Survival 2 (ISIS-2),29 and Gruppo Italiano per lo Studio della Streptochinasi nell’Infarto Miocardico 1 (GISSI 1) trials.30 Fibrinolytic therapy has no significant benefit for management of patients with UA/NSTEMI without STEMI, true posterior MI, or a presumed new LBBB, and therefore is not recommended.28, 29, 30 Table 22-4 compares characteristics of the fibrinolytic agents. Contraindications and cautions of fibrinolytic agents are presented in Table 22-5.

Prehospital Fibrinolytics

Multiple trials31, 32, 33, 34 have demonstrated that prehospital fibrinolytic administration can significantly decrease time from symptom onset to treatment.12 Compared with historical control patients, patients who received prehospital fibrinolysis achieved more rapid resolution of ST-segment elevation.32 A meta-analysis31 of six randomized trials33, 34, 35, 36, 37, 38 demonstrated improved outcomes and lower mortality with prehospital fibrinolysis.

Prehospital fibrinolysis protocols are reasonable if physicians are present in the ambulance or if well-organized EMS systems are in place and meet the following criteria: (1) paramedics are full time employees, can transmit 12-lead ECGs, and have initial and ongoing training in ECG interpretation and STEMI treatment; (2) an online medical command and a medical director with training/experience in STEMI management are available; and (3) an ongoing continuous quality-improvement program has been implemented (Class IIa, level of evidence: B).2 If the EMS are capable of providing fibrinolysis, and if the patient qualifies for fibrinolytic therapy, fibrinolysis should begin within 30 minutes of EMS arrival on scene.3

Fibrinolytic Agents

There are two major categories of fibrinolytic agents: fibrin nonselective and fibrin selective. A summary of the most commonly used fibrinolytic agents is presented below. Also see Tables 22-4 and 22-5.


First-generation nonselective fibrinolytics include streptokinase and urokinase, which activate plasminogen systemically and are not fibrin specific. IV urokinase is not approved for STEMI. Tillet and Garner39 discovered in 1933 that several strains of Streptococcus hemolyticus could dissolve human
thrombus. Streptokinase is a single chain polypeptide protein derived from β-hemolytic streptococcus. It binds to plasminogen to form the streptokinase-plasminogen activator complex and then converts plasminogen to plasmin, which initiates fibrinolysis. As described by Bates,40 early studies of IV streptokinase showed inconsistent improvement in LV function and mortality, likely because doses were inconsistent and administered too late. With improvements in both time-to-administration and consistent dosing protocol (1.5 million units of streptokinase infused over 60 minutes), patency rates at 60 to 90 minutes and at 2 to 3 hours of approximately 50% and 70%, respectively, were attained.


Absolute Contraindications

  • Any prior intracranial hemorrhage

  • Known structural cerebral vascular lesion (e.g., AVM)

  • Known malignant intracranial neoplasm (primary or metastatic)

  • Ischemic stroke within 3 months EXCEPT acute ischemic stroke within 3 hours

  • Suspected aortic dissection

  • Active bleeding or bleeding diathesis (excluding menses)

  • Significant closed head or facial trauma within 3 months

Relative Contraindications

  • History of chronic severe, poorly controlled hypertension

  • Severe uncontrolled hypertension on presentation (SBP >180 mm Hg or DBP >110 mm Hg)

  • History of prior ischemic stroke greater than 3 months, dementia, or known intracranial pathology not covered in contraindications

  • Traumatic or prolonged (greater than 10 minutes) CPR or major surgery (less than 3 weeks)

  • Recent (within 2 to 4 weeks) internal bleeding

  • Noncompressible vascular punctures

  • For streptokinase/anistreplase: prior exposure (more than 5 days ago) or prior allergic reaction to these agents

  • Pregnancy

  • Active peptic ulcer

  • Current use of anticoagulants: the higher the INR, the higher the risk of bleeding

*Viewed as advisory for clinical decision making and may not be all-inclusive or definitive.

Could be an absolute contraindication in low-risk patients with STEMI.

AVM, arteriovenous malformation; SBP, systolic BP; DBP, diastolic BP; CPR, cardiopulmonary resuscitation; INR, international normalized ratio.

Antman, JL., Anbe, DT., Armstrong, PW., et al. (2004). ACC/AHA Guidelines for the Management of Patients with ST-elevation Myocardial Infarction: A report of the American College of Cardiology/American Heart Association task force on Practice Guidelines (writing Committee to Revise the 1999 Guidelines for the Management of Patients with Acute Myocardial Infarction). JACC, e3-e170.

Streptokinase is antigenic and can cause immunologic sensitization with repeat administration. Major reactions of anaphylaxis are rare and occur in <0.5% of cases. Less severe symptoms with administration include shivering, pyrexia, rash, or hypotension that may occur in 10% of patients.41 Bleeding is the most common complication, with minor bleeding at puncture sites occurring in 3% to 4% of patients; major bleeding and stroke occurs in <1% and 1.6%, respectively, in patients older than 70 years.42

Tissue Plasminogen Activator (t-PA) and Recombinant t-PA (rt-PA; Alteplase).

The second-generation fibrinolytics are fibrin selective and have demonstrated improved patency rates for reperfusion in STEMI. The fibrinolytic t-PA occurs as a serine protease that is secreted naturally by vascular endothelium. rt-PA is known as alteplase. Both native t-PA and rt-PA (alteplase) preferentially activate plasminogen at the fibrin clot and cause lysis of thrombus, although systemic plasminogen activation occurs at clinical doses.41

Accelerated or front-loaded alteplase, weight adjusted and administered with heparin for 24 to 48 hours, has proven to be the best fibrinolytic strategy of the second-generation agents with 90-minute patency rates of approximately 82%.41 Alteplase has a short half-life (3 to 4 minutes), requiring heparin infusion for at least 24 hours after administration. Alteplase has not been associated with allergic reactions or hypotensive reactions.

Reteplase (r-PA), Tenecteplase (TNK-t-PA), and Lanoteplase (n-PA).

The third-generation fibrinolytics include reteplase, tenecteplase, and lanoteplase. STEMI treatment advancement with these third-generation agents has been in the finetuning of protocols and administration of adjunctive treatments rather than in the synthesis of new compounds.43 Reteplase, a nonglycosylated deletion mutant of wild-type t-PA,43,44 has preferential activation of fibrin-bound plasminogen, a longer half-life, enhanced fibrinolytic potency, and lower affinity for endothelial cells than does t-PA.43 Tenecteplase is a genetically engineered, multiple point mutant of t-PA that has a longer plasma half-life, allowing single IV bolus injection and more fibrin specificity than standard t-PA. Clinical trials involving reteplase and tenecteplase have found similar efficacy and safety results as with alteplase, but these agents are easier and more convenient to use because of bolus administration rather than infusion.44,45

Ancillary Anticoagulation to Support Reperfusion Therapy

To prevent reocclusion of the infarct vessel, the ACC/AHA STEMI fibrinolysis guidelines recommend ancillary anticoagulant therapy for a minimum of 48 hours (level of evidence: C) but optimally for the duration of hospitalization. Unfractionated heparin (UFH) is recommended only for the first 48 hours because of the risk of heparin-induced thrombocytopenia with prolonged UFH exposure (level of evidence: A)3 unless there are ongoing indications for anticoagulation.2,46,47 The 2004 ACC/AHA STEMI ancillary anticoagulation recommendations are2:

Jan 10, 2021 | Posted by in NURSING | Comments Off on Acute Coronary Syndromes
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