Non–ST Segment Elevation Acute Coronary Syndrome

Published on 23/05/2015 by admin

Filed under Internal Medicine

Last modified 22/04/2025

Print this page

This article have been viewed 1861 times

Chapter 17

Non–ST Segment Elevation Acute Coronary Syndrome

Paul A. Schurmann, MD and Glenn N. Levine, MD, FACC, FAHA

1. What is non–ST segment elevation acute coronary syndrome?

It is now recognized that unstable angina, non–Q wave myocardial infarction (MI), non–ST segment elevation MI, and ST segment elevation myocardial infarction (STEMI) are all part of a continuum of the pathophysiologic process in which a coronary plaque ruptures, thrombus formation occurs, and partial or complete, transient or more sustained vessel occlusion may occur (Fig. 17-1). This process is deemed acute coronary syndrome when it is clinically recognized and causes symptoms. Acute coronary syndromes can be subdivided for treatment purposes into non–ST segment elevation acute coronary syndrome (NSTE-ACS) and ST segment elevation acute coronary syndrome (STE-ACS).

Figure 17-1 Plaque rupture in the proximal left anterior descending (LAD) coronary artery has led to thrombus formation (arrow) and partial occlusion of the vessel. (Reproduced with permission from Cannon CP, Braunwald E: Unstable angina and non–ST elevation myocardial infarction. In Libby P, Bonow R, Mann D, et al, editors: Braunwald’s heart disease: a textbook of cardiovascular medicine, ed 8, Philadelphia, 2008, Saunders, p. 1179)

The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines have traditionally used the terms unstable angina/non–ST elevation MI (UA/NSTEMI) when referring to patients with NSTE-ACS, whereas the European Society of Cardiology (ESC) guidelines prefer the term acute coronary syndrome without ST elevation.

2. What is the current definition of a myocardial infarction?

According to the 2007 joint ESC/ACCF/AHA/World Heart Federation statement, the term myocardial infarction should be used “when there is evidence of myocardial necrosis in a clinical setting consistent with myocardial ischemia.” For patients with acute coronary syndromes, this includes detection of the rise or fall of cardiac biomarkers (preferably troponin) with at least one value above the ninety-ninth percentile of the upper reference limit, and evidence of myocardial ischemia with at least one of the following:

Symptoms of ischemia

Electrocardiogram (ECG) changes indicative of new ischemia (new ST-T changes or new left bundle branch block)

Development of pathologic Q waves in the ECG

Imaging evidence of new loss of viable myocardium or new regional wall motion abnormalities

Note that using this definition, patients admitted with anginal chest pains and troponin elevations of as little as 0.04 to 0.08 ng/mL may now be diagnosed as having myocardial infarction, depending on locally established ninety-ninth percentile ranges of troponin values.

3. What other conditions besides epicardial coronary artery disease and acute coronary syndrome can cause elevations in troponin?

Although troponins have extremely high myocardial tissue specificity and sensitivity with new assay, numerous conditions besides epicardial coronary artery disease and acute coronary syndromes may cause elevations of troponins. Such conditions include noncoronary cardiac disease (myocarditis, acute congestive heart failure [CHF] exacerbation, cardiac contusion, apical ballooning syndrome), acute vascular pathology (hypertensive crisis, aortic dissection, pulmonary embolus), infiltrative diseases (amyloidosis, sarcoidosis), and systemic illnesses (anemia, chromic kidney disease [CKD], hypothyroidism, hypoxemia). Conditions that have been associated with elevation of troponin levels are given in Table 17-1.

TABLE 17-1

CONDITIONS OTHER THAN CORONARY ARTERY DISEASE ASSOCIATED WITH ELEVATION IN CARDIAC TROPONIN

System	Causes of Troponin Elevation
Cardiovascular	Acute aortic dissection Arrhythmia Medical ICU patients Hypotension Heart failure Apical ballooning syndrome Cardiac inflammation Endocarditis, myocarditis, pericarditis Hypertension Infiltrative disease Amyloidosis, sarcoidosis, hemochromatosis, scleroderma Left ventricular hypertrophy
Myocardial injury	Blunt chest trauma Cardiac surgeries Cardiac procedures Ablation, cardioversion, percutaneous intervention Chemotherapy Hypersensitivity drug reactions Envenomation
Respiratory	Acute PE ARDS
Infectious/Immune	Sepsis/SIRS Viral illness Thrombotic thrombocytopenic purpura
Gastrointestinal	Severe GI bleeding
Nervous system	Acute stroke Ischemic stroke Hemorrhagic stroke Head trauma
Renal	Chronic kidney disease
Endocrine	Diabetes Hypothyroidism
Musculoskeletal	Rhabdomyolysis
Integumentary	Extensive skin burns
Inherited	Neurofibromatosis Duchenne muscular dystrophy Klippel-Feil syndrome
Others	Endurance exercise Environmental exposure Carbon monoxide, hydrogen sulfide

ARDS, Acute respiratory distress syndrome; GI, gastrointestinal; ICU, intensive care unit; PE, pulmonary embolism; SIRS, systemic inflammatory response syndrome.

Reproduced with permission from Januzzi JL Jr: Causes of Non-ACS Related Troponin Elevations. Available at http://www.cardiosource.org. Accessed February 16, 2013.

4. What are the factors that make up the Thrombolysis in Myocardial Infarction (TIMI) Risk Score?

The seven factors that make up the TIMI Risk Score are shown in the list that follows. Each factor counts as 1 point. A total score of 0 to 2 is a low TIMI Risk Score and is associated with a 4.7% to 8.3% 2-week risk of adverse cardiac events; a total score of 3 to 5 is an intermediate TIMI Risk Score and is associated with a 13.2 to 26.2% 2-week risk of adverse cardiac events; and a total score of 6 to 7 is a high TIMI Risk Score and is associated with a 40.9% risk of adverse cardiac events.

Age greater than 65 years

Three or more risk factors for coronary artery disease (CAD)

Prior catheterization demonstrating CAD

ST segment deviation

Two or more anginal events within 24 hours

Acetylsalicylic acid (ASA) use within 7 days

Elevated cardiac markers

5. What are the components of the Global Registry of Acute Coronary Events (GRACE) ACS Risk Model (at the time of admission)?

The components of the GRACE ACS Risk Model at the time of admission consist of:

Age

Heart rate (HR)

Systolic blood pressure (SBP)

Creatinine

Congestive heart failure Killip class

Cardiac arrest at admission (yes/no)

ST segment deviation (yes/no)

Elevated cardiac enzymes/markers

Scores are calculated based on established criteria. Calculation algorithms are easily downloadable to computers and handheld devices. A low-risk score is considered 108 or less and is associated with a less than 1% risk of in-hospital death. An intermediate score is 109 to 140 and is associated with a 1% to 3% risk of in-hospital death. A high-risk score is greater than 140 and associated with a more than 3% risk of in-hospital death.

6. What other biomarkers and measured blood levels have been shown to correlate with increased risk of adverse cardiovascular outcome?

Multiple biomarkers can be measured in the blood, but it is important to understand what they represent. The most common are creatine kinase–MB (CK-MB) and troponin T and I levels, which are related to myocardial injury and are independent predictors of adverse cardiovascular outcomes.

Common inflammatory biomarkers like C-reactive protein (CRP), matrix metalloproteinase (MMP-9), myeloperoxidase (MPO), B-type natriuretic peptide (BNP), and ischemia modified albumin (IMA) have been shown to be independent predictors of adverse cardiovascular outcomes. How these findings should be used in clinical practice is subject to continued investigation and debate. Additional markers are expected to emerge over the next several years.

7. What are the differences between the oral antiplatelet agents?

The first thienopyridine was ticlopidine (Ticlid), which was used along with aspirin for the prevention of stent thrombosis. Ticlopidine was replaced in clinical practice by clopidogrel, which was a once-daily agent with similar efficacy to ticlopidine, but better tolerated.

More recently, the thienopyridine prasugrel and the triazolopyrimidine ticagrelor have been approved for use. These two agents have been studied in patients with ACS undergoing stent implantation. Like clopidogrel, both are P2Y₁₂ blockers. Both these newer agents are more potent than clopidogrel, leading to greater and more reliable platelet inhibition than clopidogrel. They also both have a shorter onset of action than clopidogrel. Like clopidogrel, prasugrel irreversibly inhibits the platelet. Although ticagrelor does not irreversibly inhibit the platelet, there nevertheless is effective platelet inhibition for days following discontinuation of ticagrelor. The characteristics of these 3 agents are summarized in Table 17-2.

TABLE 17-2

CHARACTERISTICS OF THE THREE ORAL P2Y₁₂ INHIBITOR ANTIPLATELET AGENTS USED IN THE TREATMENT OF PATIENTS WITH NSTE-ACS

NSTE-ACS, Non–ST segment elevation acute coronary syndrome.

Reproduced with permission from Hamm CW, Bassand JP, Agewall S, et al: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32:2999-3054, 2011.

8. What antiplatelet agents are recommended in the ACCF/AHA and ESC guidelines?

Both organizations recommend that aspirin should be administered as soon as possible and that in patients with true aspirin allergies or aspirin contraindications, clopidogrel should be administered as a substitute for aspirin.

The ACCF/AHA guidelines recommend administration of either clopidogrel, ticagrelor, or a glycoprotein (GP) IIb/IIIa inhibitor (in addition to aspirin) in patients who are to be treated with an early invasive strategy. Administration of both an oral P2Y₁₂ inhibitor and an intravenous antiplatelet agent can be considered in certain circumstances in which a patient with high risk characteristics is to be treated with an early invasive strategy. Prasugrel can be considered as the P2Y₁₂ agent in patients who are undergoing PCI with coronary stent implantation. The ACCF/AHA guidelines recommend clopidogrel or ticagrelor (in addition to aspirin) in patients to be treated with an initial conservative strategy.

The ESC guidelines recommend that all patients receive a P2Y₁₂ inhibitor, with ticagrelor or prasugrel generally being preferred over clopidogrel. The additional use of GP IIb/IIIa inhibitors in high-risk patients is also recommended.

The antiplatelet recommendations of the ACCF/AHA and the ESC NSTE-ACS guidelines are summarized in Table 17-3.

TABLE 17-3

ACCF/AHA AND ESC GUIDELINES FOR ANTIPLATELET THERAPIES IN PATIENTS WITH NSTE-ACS

ACCF/AHA Guidelines

Class I

Aspirin

Clopidogrel if ASA allergic/intolerant

Clopidogrel or ticagrelor in addition to ASA if initial conservative strategy

Clopidogrel, ticagrelor, or GP IIb/IIIa (in addition to ASA) upstream if early invasive strategy

Prasugrel (in addition to ASA) at the time of the percutaneous coronary intervention

Clopidogrel, ticagrelor or prasugrel should be administered at least 12 months in patient who underwent percutaneous coronary intervention.

Class IIa

It is reasonable to omit GP IIb/IIIa if early invasive strategy and patient treated with bivalirudin and with clopidogrel (>6 hr).

For initial conservative strategy, if already on ASA and clopidogrel (or ticagrelor) and has recurrent ischemia, add GP IIb/IIIa inhibitors.

Class IIb

Clopidogrel and GP IIb/IIIa (in addition to ASA) upstream if early invasive strategy

Class III—No benefit

Abciximab should not be administered to patient in whom PCI is not planned.

Class III—Harm

Prasugrel use in patient with prior history of stroke or TIA for whom PCI is planned

ESC Guidelines

Class I

Aspirin should be given to all patients without contraindications.

P2Y₁₂ inhibitor (in addition to ASA) for all patients, except if they are high risk for bleeding.

Ticagrelor is recommended for all patients at mod-high ischemic events regardless of initial treatment strategy.

Prasugrel is recommended for P2Y₁₂ inhibitor naive patient with known coronary anatomy and planned for PCI without contraindications.

Clopidogrel is recommended for patients who cannot receive ticagrelor or prasugrel.

In patients considered for invasive procedure/PCI, 600 mg loading dose of clopidogrel may be used.

GP IIb/IIIa (in addition to dual oral antiplatelet agents) in high-risk patients (elevated troponin, visible thrombus) is recommended if the risk of bleeding is low.

Class IIa

Eptifibatide and tirofiban added to aspirin should be considered prior to angiography in high-risk patients not preloaded with P2Y₁₂ inhibitors.

Class IIb

Platelets function analysis or genotyping might be considered in selected cases where result may alter the management.

Class III

NSAIDs (nonselective or COX-2 inhibitors) should not be administered during UA/NSTEMI, except aspirin.

Routine GP IIb/IIIa inhibitors with ASA and/or P2Y₁₂ inhibitor is not recommended, particularly in those undergoing medical management without PCI.

ACCF, American College of Cardiology Foundation; AHA, American Heart Association; ASA, acetylsalicylic acid; ESC, European Society of Cardiology; GP, glycoprotein; NSAID, nonsteroidal antiinflammatory drug; NSTE-ACS, non–ST segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; TIA, transient ischemic attack; UA/NSTEMI, unstable angina/non–ST segment elevation myocardial infarction.

Modified from Wright RS; Anderson JL, Adams CD, et al: 2011 ACCF/AHA Focused Update of the Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction (Updating the 2007 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 123:2022-2060, 2011; Jneid H, Anderson JL, Wright RS, et al: 2012 ACCF/AHA Focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update). J Am Coll Cardiol 2012:645-81; and Hamm CW, Bassand JP, Agewall S, et al: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32:2999-3054, 2011.

9. What are the differences between the intravenous antiplatelet agents?

Eptifibatide (Integrilin) and tirofiban (Aggrastat) are small-molecule GP IIb/IIIa inhibitors that are used both for “upfront” treatment of NSTE-ACS and during percutaneous coronary intervention (PCI). Abciximab (ReoPro) is an antibody fragment that is used predominantly at the time of PCI (although there is a very specific circumstance in which it can be considered in NSTE-ACS patients before PCI is performed). Eptifibatide and tirofiban lead to reversible platelet inhibition, whereas abciximab leads to irreversible platelet inhibition. All 3 agents lead to a high degree of platelet inhibition, are associated with a small but real increased risk of major bleeding, and are associated with a small (1% to 4%) incidence of thrombocytopenia. Thrombocytopenia can occur rapidly and be profound, and careful monitoring of platelet counts is warranted when these agents are begun. The characteristics of these 3 agents are summarized in Table 17-4.

TABLE 17-4

CHARACTERISTICS OF THE 3 INTRAVENOUS ANTIPLATELET AGENTS USED IN THE TREATMENT OF PATIENTS WITH NSTE-ACS

CABG, coronary artery bypass graft; GP, glycoprotein.

Modified with permission from Hamm CW, Bassand JP, Agewall S, et al: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32:2999-3054, 2011.

10. What anticoagulant agents are recommended by the ACCF/AHA and ESC guidelines?

The ACCF/AHA guidelines give a Class I recommendation to unfractionated heparin (UFH), enoxaparin, fondaparinux, and bivalirudin.

The ESC guidelines place a strong emphasis on the prevention of bleeding complications and preferentially recommend fondaparinux, with a single bolus of UFH (85 IU/kg or 60 IU/kg in the case of concomitant use of GP IIb/IIIa) at the time of the PCI. If fondaparinux is not available, enoxaparin (1 mg/kg twice daily) is recommended. If fondaparinux or enoxaparin are not available, UFH with a target aPTT of 50-70 sec (or other low molecular weight heparin) is recommended.

Bivalirudin plus provisional GP IIb/IIIa inhibitors are recommended as an alternative to UFH plus GP IIb/IIIa inhibitors, particularly in patients with a high risk of bleeding who are subject to invasive strategy. Anticoagulant agents recommendations are summarized in Table 17-5.

TABLE 17-5

ACCF/AHA AND ESC GUIDELINES FOR ANTITHROMBIN THERAPIES IN PATIENTS WITH NSTE-ACS∗

ACCF/AHA Guidelines

Class I

UFH (early invasive or initial conservative strategies)

Enoxaparin (early invasive or initial conservative strategies)

Fondaparinux (early invasive or initial conservative strategies)

Bivalirudin (early invasive strategy only)

Fondaparinux preferred for conservative strategy in patients with increased risk of bleeding.

For initial conservative treatment, enoxaparin or fondaparinux preferred over UFH.

ESC Guidelines

Class I

Anticoagulation is recommended for all patients in addition to antiplatelet therapy.

Anticoagulant should be selected according to risk of both ischemic and bleeding events.

In conservative treatment, anticoagulation should be maintained up to hospital discharge.

Fondaparinux (2.5 mg SC daily) is recommended as having the best efficacy–safety profile.

If initial anticoagulant is fondaparinux, a single bolus of UFH 85 IU/kg or 60 IU/kg in the case of concomitant use of GP IIb/IIIa should be added at the time of PCI.

Enoxaparin (1 mg/kg twice daily) is recommended when fondaparinux is not available.

If fondaparinux or enoxaparin are not available, UFH with a target PTT of 1.5 to 2.5 times control is indicated.

Bivalirudin plus provisional GP IIb/IIIa are recommended as an alternative to UFH plus GP IIb/IIIa particularly in patients with a high risk of bleeding planned for urgent or early invasive strategy.

Class III

Crossover of heparins (UFH and LMWH) is not recommended.

ACCF, American College of Cardiology Foundation; AHA, American Heart Association; ESC, European Society of Cardiology; GP, glycoprotein; LMWH, low-molecular-weight heparin; NSTE-ACS, non–ST segment elevation acute coronary syndrome; PCI, percutaneous coronary intervention; PTT, partial thromboplastin time; SC, subcutaneous; UFH, unfractionated heparin.

Modified from Wright RS; Anderson JL, Adams CD, et al: 2011 ACCF/AHA Focused Update of the Guidelines for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction (Updating the 2007 Guideline): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation. 123:2022-2060, 2011; and Hamm CW, Bassand JP, Agewall S, et al: ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: The Task Force for the management of acute coronary syndromes (ACS) in patients presenting without persistent ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 32:2999-3054, 2011.

11. What is the recommended dosing of unfractionated heparin?

The dosing recommendations vary slightly between ACCF/AHA and ESC, as well as with the American College of Chest Physicians (ACCP).

ACCF/AHA: 60 U/kg bolus (max. 4000 U), then initial infusion of 12 U/kg (max. initial infusion 1000 U/hr). Target anti-Xa is 0.3 to 0.7; target activated partial thromboplastin time (aPTT) is 1.5 to 2.5 times control (60 to 80 seconds per ACCP guidelines).

ESC: 60 to 70 U/kg bolus (max. 5000 U), then initial infusion of 12 to 15 U/kg (initial max. 1000 U/hr). Target aPTT is 50 to 75 seconds (1.5 to 2.5 times control).

12. Which patients with NSTE-ACS should be treated with a strategy of early catheterization and revascularization?

Studies performed in the 1980s comparing a strategy of early catheterization and revascularization with a strategy of initial medical therapy failed to show benefits of early catheterization and revascularization. More recent studies have demonstrated benefits of early catheterization and revascularization in appropriately selected patients with high-risk features.

An early invasive strategy is considered to be the performance of catheterization (and PCI if appropriate) within 2 to 48 hours of admission. Patients who should be treated with early invasive strategy are those without clear contraindications to catheterization, revascularization, and elevated risk for clinical events.

The ACCF/AHA criteria for elevated risk for clinical events (Fig. 17-2) include recurrent angina/ischemia, elevated troponin, new ST depression, CHF exacerbation, reduced left ventricular (LV) function, high-risk findings on noninvasive testing, hemodynamic instability, sustained ventricular tachycardia (VT), PCI within 6 months, prior coronary artery bypass graft (CABG), and high risk score (TIMI ≥ 6, GRACE > 140).