The goals of treatment in acute MI are stabilization of the patient and salvage of as much myocardium as possible. A number of general measures should be performed in all patients. In patients with ST elevation—who are at highest risk for complications and have ongoing cardiomyocyte necrosis—immediate reperfusion of the infarct artery should be attempted. The management of acute MI is summarized in Table 8–2.
Early recognition of symptoms of myocardial ischemia may lead to faster treatment and salvage of myocardium. Therefore, it is recommended that patients at risk for MI be educated about the symptoms suggestive of acute MI and call for emergency help immediately if they have these symptoms.
Aspirin, 162–325 mg, should be given immediately. Continuous cardiac monitoring, oxygen, and sublingual nitroglycerin should be administered to all patients with suspected acute MI. Communities usually have organized protocols for ambulance personnel regarding (1) whether or not they should obtain a 12-lead ECG, (2) whether there are designated hospitals that receive patients in whom an acute MI is suspected, or (3) whether the patient should be taken to the nearest emergency department. In some regions of the world, fibrinolytic treatment is initiated in the ambulance, based on a 12-lead ECG.
Emergency Department Therapy
On arrival, all patients with suspected acute MI should have a 12-lead ECG performed immediately. If aspirin has not been given, then 162–325 mg of aspirin should be administered immediately. All patients with suspected MI should have continuous cardiac ECG monitoring, and intravenous access (two separate intravenous lines) should be gained in all patients. Sublingual nitroglycerin and intravenous morphine should be administered if patients have active chest pain. Oxygen saturations should be monitored noninvasively, rather than by arterial blood gas measurement. Supplemental oxygen, 2–4 L/min, should be given to all patients, particularly if they are hypoxemic. A portable chest radiograph should be ordered but should not delay reperfusion, unless a diagnosis of aortic dissection is strongly considered. Echocardiography may be considered if the diagnosis of MI remains in doubt (eg, equivocal history, uninterpretable ECG). Oral β-blockers should be administered to all patients with acute MI, unless there is a contraindication, such as hypotension, bradycardia, or asthma. This has been shown to improve outcomes and limit the size of infarction. Intravenous β-blockers could be considered when there is hypertension or tachyarrhythmia, for example (Table 8–3). However, they should be avoided in patients with signs of heart failure, in those with contraindications to β-blockers, and in those at high risk for cardiogenic shock (age > 70 years, heart rate > 110/min or < 60/min, systolic blood pressure < 120 mm Hg, or prolonged time since the onset of symptoms).
Table 8–3. Standard Doses of Commonly Used Agents in Patients with Acute Myocardial Infarction ||Download (.pdf)
Table 8–3. Standard Doses of Commonly Used Agents in Patients with Acute Myocardial Infarction
Initial bolus of 1 mg/kg and 2 mg/min infusion; additional bolus doses to 3 mg/kg may be necessary
For symptomatic arrhythmias and sustained ventricular tachycardia and ventricular fibrillation, not arrest
20 mg/min–1 g, then 2–4 mg/min drip
May cause hypotension, QRS or QT lengthening, or toxicity
1–2 g over 1–2 min or infusion of 8 g over 24 h
Observe for changes in heart rate, blood pressure
15 mg/min × 10 min, then 1 mg/min × 6 h and 0.5 mg/min × 24 h
For refractory ventricular tachycardia, ventricular fibrillation and arrest
250 mcg/kg IV loading dose, then 25–50 mcg/kg/min to maximum dose of 300 mcg/kg/min
Very short half-life
5 mg every 5 min IV × 3 then 25–50 mg every 12 h orally
Long duration of action; may exacerbate heart failure
0.1 mg/kg over 5 min IV, followed by 20–40 mg every 6 h orally
Long duration of action; may exacerbate heart failure
Calcium channel blockers
20–25 mg IV test dose, then 10–15 mg/h as needed; 90–120 mg three times daily orally
May exacerbate heart failure
Inotropes and pressors
Initial bolus of 0.75 mg/kg, then 5–10 mg/kg/min
May exacerbate ischemia
Begin at 2.5 mcg/kg/min and titrate to effect
Increases in heart rate > 10% may exacerbate ischemia
Start at 2 mcg/kg/min, titrate to effect
May exacerbate pulmonary congestion and ischemia
Start at 2 mcg/min, titrate to effect
Temporizing treatment only
Begin at 10 mcg/min IV, titrate to effect
Avoid reducing blood pressure by > 10% if normotensive, > 30% if hypertensive
Begin at 0.1 mcg/kg/min, titrate to effect
Mean dose 50–80 mcg/kg/min
2 mcg/kg bolus followed by 0.01 mcg/kg/min infusion, can increase by 0.005 to maximum infusion 0.03 mcg/kg/min
Hold diuretics and other vasodilators. Keep systolic blood pressure > 100 mm Hg
5000-unit bolus followed by 1000 units/h adjusted by aPTT
Less efficacious than LMWH
1 mg/kg SQ every 12 h, can give immediate 30-mg bolus intravenously if necessary
Hard to reverse effects; avoid in patients with renal failure
120 international units/kg every 12 h
Avoid in patients with renal failure
0.25 mg/kg followed by 0.125 mcg/kg/min × 12 h, maximum time–24 h
Care necessary if renal failure; thrombocytopenia greater with repeated use
180 mcg/kg bolus × 2 (30 min later) followed by 2 mcg/kg/min for as long as 96 h for ACS, 24 h post PCI
Care necessary if renal failure
0.4 mcg/kg/min × 30 min followed by 0.1 mcg/kg/min for up to 108 h for ACS, 12–19 h for PCI
Care necessary if renal failure
600 mg loading dose, then 75 mg/day × at least 1 month, preferably for 12 months
60 mg loading dose, then 10 mg daily for 12 months
Contraindicated if prior stroke or TIA, weight < 60 kg, or age > 75 years
Ticagrelor 180-mg loading dose then 90 mg twice daily for 12 months
May cause bradycardia or shortness of breath
An anticoagulant should be administered to all patients with acute MI, unless a contraindication exists. In patients with ST elevation who receive fibrinolytics, 48 hours of anticoagulant should be administered. Acceptable choices for anticoagulants include unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and fondaparinux. For patients with ST elevation undergoing primary PCI, acceptable choices for anticoagulants include UFH, LMWH, and bivalirudin. UFH is preferred to LMWH in most institutions for primary PCI because it has a short half-life, it can be turned off rapidly if there is a complication during invasive therapy, and it can be monitored during procedures with a bedside activated clotting time test. In contrast, LMWHs have a long half-life, and there is no bedside test of their anticoagulant efficiency.
All patients with STEMI who seek medical care within the first 12 hours after symptom onset should be considered for urgent reperfusion of the infarct-related artery, but the earlier therapy is begun, the greater the benefit. In addition, those patients who seek medical care within 12–24 hours of symptom onset may be considered for reperfusion, particularly if chest pain is ongoing or heart failure or shock has developed, but the benefit of reperfusion therapies after more than 12 hours is less well established. The definitive therapies for reperfusion in STEMI are fibrinolysis or PCI. Both of these strategies improve patency of the infarct-related artery, reduce infarct size, and lower mortality rates. Therefore, one or the other method should be performed as quickly as possible. The goal of reperfusion therapies in the United States is a door-to-needle time of 30 minutes (for fibrinolysis) and a door-to-balloon inflation time of less than 90 minutes (for PCI). PCI has been shown to be superior to fibrinolysis when it is performed without significant delay by experienced clinicians in experienced centers (Figure 8–3). However, significant delays in performing PCI reduce its benefit over fibrinolytic therapy. There are special cases where primary PCI is always preferred over fibrinolysis: cardiogenic shock, severe CHF or pulmonary edema (Killip class III), or if there are contraindications to fibrinolysis (Table 8–4). These patients may require insertion of an IABP and may benefit from mechanical reperfusion with primary PCI. The different management of patients with these high-risk clinical features underscores the need for careful clinical examination of all patients with chest pain.
Percutaneous coronary intervention (PCI) versus fibrinolysis for ST elevation myocardial infarction (STEMI). Short-term (4–6 weeks; A) and long-term (B) outcomes for various end points shown are plotted for STEMI patients randomized to PCI or fibrinolysis for reperfusion in 23 trials (n = 7739). Primary angioplasty for acute STEMI improves both short- and long-term outcomes. CVA, cerebrovascular accident; Hem. stroke, hemorrhagic stroke; Rec. isch., recurrent ischemia; ReMI, recurrent myocardial infarction. (Modified, with permission, from Keeley EC, et al. The Lancet. 2003;361:13 and Antman EM, et al. J Am Coll Cardiol. 2004;44:671.)
Table 8–4. Contraindications for Fibrinolysis Use in STEMI ||Download (.pdf)
Table 8–4. Contraindications for Fibrinolysis Use in STEMI
Any prior ICH
Known structural cerebral vascular lesion (eg, AVM)
Known malignant intracranial neoplasm (primary or metastatic)
Ischemic stroke within previous 3 months
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding menses)
Significant closed head or facial trauma within 3 months
Severe uncontrolled hypertension (SBP > 180 mm Hg and/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 (> 10 minutes) CPR or major surgery in previous 3 weeks
Recent internal bleeding (within 4 weeks)
Noncompressible vascular punctures
For streptokinase/anistreplase: prior exposure (> 5 days ago) or prior allergic reaction to these agents
Active peptic ulcer
Current use of anticoagulants: the higher the INR, the higher the risk of bleeding
Recent data suggest that all patients with STEMI, whether they undergo primary PCI or fibrinolytic therapy, benefit from early administration of a thienopyridine in addition to aspirin. Acceptable alternatives include clopidogrel, prasugrel (only if undergoing primary PCI), or ticagrelor. However, thienopyridines may cause an increase in bleeding complications if the patient undergoes CABG surgery.
These patients should not be treated with fibrinolytics. The definitive management of NSTEMI involves anticoagulation, platelet inhibition, and consideration for an early invasive strategy (ie, routine coronary angiography with or without PCI during the index hospitalization).
For detailed discussion of NSTEMI, see Chapter 7.
All patients with acute MI should be admitted for continuous cardiac monitoring. Patients should have bed rest for the first 12–24 hours following MI and reperfusion, but in the absence of ongoing ischemia, they should be mobilized after this time. All patients should receive the appropriate cardiac diet, adhering to the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATP III) dietary guidelines, as well as education regarding the necessary dietary changes they should make after discharge.
Within the first 24 hours of presentation, the long-term medical management of patients with both STEMI and NSTEMI should be commenced. Angiotensin-converting enzyme (ACE) inhibitors should be given on day 1, if the patient's blood pressure allows, particularly in those with anterior MI or impaired left ventricular function. ACE inhibitors reduce left ventricular remodeling and heart failure and should be continued long-term. β-Blockade should have already been started in the emergency department and should be continued orally in all patients, unless there are absolute contraindications, and should also be continued long-term. Aspirin, 162–325 mg daily, should be administered initially, then 81 mg daily for life. Thienopyridines (clopidogrel, prasugrel, or ticagrelor) should be continued for 12 months. Hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statin therapy) should be given soon after MI and should be continued at high dose long-term.
During hospitalization, all patients should be educated about adhering to therapeutic lifestyle changes, including dietary and lifestyle measures, smoking cessation, and medication compliance. Patients should be referred to a cardiac rehabilitation program to consolidate these messages and develop an appropriate exercise regimen. This has been shown to reduce mortality after MI.
Primary PCI versus Fibrinolysis
The goal of reperfusion is to rapidly restore blood flow to the myocardium to prevent ongoing ischemic cell death. Therefore, whichever means can achieve reperfusion most quickly should be used. Primary PCI results in improved patency rates of the infarct-related artery, as well as improved TIMI flow grade, compared with fibrinolysis. In general, the patency rate with primary PCI is 90% or higher, whereas with thrombolysis, the rate is about 65% and recurrent events are more common. With modern advances, coronary stenting has further improved long-term outcomes over balloon angioplasty alone. PCI has therefore been widely accepted as the treatment of choice for STEMI in centers that can perform primary PCI rapidly and effectively (Figure 8–4). However, very early after the onset of symptoms, when the thrombus in the infarct-related artery is still soft, fibrinolysis may recanalize the artery as quickly as, if not more so than, primary PCI. This is true in the first hour and possibly the first 3 hours after symptom onset. Therefore, fibrinolysis is an acceptable treatment in these early time points. However, after 3 hours, primary PCI has a clear benefit over fibrinolysis and should be considered the preferred therapy. It bears restating that primary PCI should only be performed in centers skilled in the treatment of STEMI that can achieve rapid reperfusion, with a goal door-to-balloon inflation time of 90 minutes.
Primary percutaneous coronary intervention (PCI) for acute myocardial infarction (MI). A: Initial angiography of a patient presenting with acute anterior ST elevation myocardial infarction (STEMI) shows an occluded left anterior descending (LAD) coronary artery (arrow). B: Following angioplasty and stenting, patency of the LAD is restored.
In deciding whether elderly patients with acute STEMI should undergo PCI or fibrinolytic therapy, the risks and benefits must be weighed carefully. Elderly patients with STEMI are at high risk for increased morbidity and mortality with thrombolytic agents. Indeed, some studies suggest that these agents have no benefit in this group. On the other hand, PCI is clearly beneficial. However, if PCI cannot be accomplished, individual decisions concerning the risk (which is substantial, especially in regard to intracranial bleeding) and the potential benefits must be balanced. Given the high (20–30%) mortality rate from STEMI in the elderly, some increased risk may be reasonable.
There are a number of fibrinolytic agents that have been successfully used in acute MI. Table 8–5 shows the currently approved agents for use in the United States. A brief discussion of each is warranted before deciding on the most appropriate agent. Plasmin, the key ingredient in the fibrinolytic system, degrades fibrin, fibrinogen, prothrombin, and a variety of other factors in the clotting and complement systems. This effect inhibits clot formation and can lead to bleeding. Patients with acute MI and ST segment elevation have little evidence of spontaneous or intrinsic fibrinolysis, despite the intense thrombotic stimulus present. This may be due in part to increased levels of circulating plasminogen activator inhibitor (PAI-1) in plasma or PAI-1 that is elaborated locally from platelets. The pharmacologic administration of fibrinolytic agents (see Table 8–5) to such patients seems reasonable. Plasminogen activators can be administered intravenously or directly into the coronary artery. Although more rapid patency occurs with local administration and lower doses can be used, given the need for early treatment, plasminogen activators are generally administered intravenously.
Table 8–5. Fibrinolytic Agents ||Download (.pdf)
Table 8–5. Fibrinolytic Agents
1,500,000 units over 1 h
Aspirin, ± heparin
Tissue plasminogen activator
15 mg bolus, then 50 mg over 30 min and 35 mg over next 60 min
Aspirin, heparin essential
Patients weighing less than 65 kg
1.25 mg/kg over 3 h, 10% of dose as initial bolus
3,000,000 units over 1 h
Aspirin, ± heparin
10 mg initial bolus, second 10-mg bolus after 30 min
Aspirin, heparin essential
< 60 kg: 30-mg bolus
Aspirin, heparin essential
60−70 kg: 35-mg bolus
71−80 kg: 40-mg bolus
81−90 kg: 45-mg bolus
> 90 kg: 50-mg bolus
In addition to invoking fibrinolysis and inhibiting clotting by degrading clotting factors, all plasminogen activators enhance clot formation. These effects seem greater with nonspecific plasminogen activators such as streptokinase and urokinase and could partly explain why fibrin-specific activators such as t-PA open arteries more rapidly. The enhancement of coagulation by plasminogen activators suggests an important role for the concomitant use of antithrombotic agents.
All fibrinolytic agents increase the risk of bleeding, and therefore, patients at high risk for life-threatening bleeding should not be given fibrinolysis (see Table 8–4).
Streptokinase is derived from streptococcal bacteria and activates plasminogen indirectly, forming an activator complex with a slightly longer half-life than streptokinase alone (23 minutes versus 18 minutes after a bolus). Because it activates both circulating plasminogen and plasminogen bound to fibrin, both local and systemic effects occur; that is, circulating fibrinogen degrades substantially (fibrinogenolysis, as well as fibrinolysis, occurs).
Because antibodies to the streptococci exist in many patients, allergic reactions can occur; anaphylaxis is rare, however, and the use of corticosteroids to avoid allergic reactions is no longer recommended. When streptokinase is administered intravenously, a large dose is necessary to overcome antibody resistance. Because a dose of 250,000 units will suffice in 90% of patients, the recommended dose of 1.5 million units over a 1-hour period is generally more than adequate to overcome resistance. Patients who are known to have had a severe streptococcal infection or to have been treated with streptokinase within the preceding 5 or 6 months (or longer) should not receive the agent.
Rapid administration of streptokinase, even at the recommended dose, can cause a substantial reduction in blood pressure. Although this might be considered a potential benefit of the agent, it may also be detrimental. The rate of the infusion should therefore be reduced in response to significant hypotension, and the blood pressure should be monitored closely. Because streptokinase is more procoagulant than other thrombolytic agents, it should not be surprising that patients benefit to a greater extent from the concomitant use of potent antithrombins such as hirudin. However, in combination with glycoprotein (GP) IIbIIIa inhibitors, streptokinase seems to be associated with markedly increased bleeding rates.
Urokinase is a direct activator of plasminogen. It has a shorter half-life than streptokinase (14 ± 6 minutes) and is not antigenic. Its effects on both circulating and bound-to-fibrin plasminogen are similar to those from streptokinase. It is therefore difficult to understand why intravenous doses of urokinase (2.0 million units as bolus or 3 million units over 90 minutes) seem to induce coronary artery patency more rapidly than does streptokinase. There is substantial synergism between urokinase and t-PA.
Tissue Plasminogen Activator
The initial human t-PA was made by recombinant DNA technology. The half-life in plasma was short (4 minutes) as a bolus but longer (46 minutes) with prolonged infusions. Despite the short half-life, lytic activity persisted for many hours after clearance of the activator. Although t-PAs are considered “fibrin-specific,” no activator is totally fibrin-specific, and fibrin specificity is lost at higher doses. At clinical doses, however, less fibrinogen degradation took place than with nonspecific activators. t-PA clearly opened coronary arteries more rapidly than nonspecific activators, and this is likely why its use improved mortality rates. Bleeding was not less, and there was a slight increase in the number of intracranial bleeds, which was in part due to the need for dosage adjustment for lighter-weight patients.
The original regimen for the use of t-PA was 100 mg over 3 hours: 10 mg as a bolus, followed by 50 mg over the first hour and 40 mg over the next 2 hours. Patients who weighed less than 65 kg received 1.25 mg/kg over 3 hours with 10% of the total dose given as a bolus. An alternative front-loaded regimen was found to be more effective and included an initial bolus of 15 mg, followed by 50 mg over 30 minutes and 35 mg over the next 60 minutes. Doses higher than 100 mg are associated with a higher incidence of intracranial bleeding.
Reteplase, a mutant form of t-PA, lacks several of the structural areas of the parent molecule (the finger domain, kringle 1, and the epidermal growth factor domain). It is less fibrin-specific (causes more systemic degradation of fibrinogen) than the parent molecule and has a longer half-life. Accordingly, it is used as a double bolus of 10 units initially followed by a second bolus 30 minutes later, and this requires no adjustment for patient weight. Although not shown to be superior to t-PA, many clinicians have elected to use reteplase because of the convenience of the double bolus administration.
Tenecteplase is also a mutant form of t-PA. It has substitutions in the kringle 1 and protease domains to increase its half-life, increase its fibrin specificity, and reduce its sensitivity to its native inhibitor (PAI-1). Although not shown to be superior to t-PA, tenecteplase is generally being used in preference to the parent molecule because of the convenience of a single bolus dose.
Regardless of the fibrinolytic agent used, all patients should receive aspirin and heparin (either UFH or LMWH) to counteract the procoagulant effect of the fibrinolytic agent.
Intravenous heparin, used with plasminogen activators, improves the rapidity with which patency is induced; it is essential for maintaining coronary patency, especially with t-PA–type agents. Its use is less necessary after treatment with streptokinase, probably because of the anticoagulant effects of fibrinogen depletion and degradation products.
The standard dose of UFH is usually a bolus of 5000 units, followed by a 1000-unit-per-hour infusion until the partial thromboplastin time can be used to titrate a dose between 1.5 and 2 times the normal range. It has become clear that optimal titration of UFH is problematic and that if the activated partial thromboplastin time is either too high or too low, some benefit is lost. For this reason, the use of LMWH has been recommended. With the exception of patients with renal failure, a dose of 1 mg/kg of enoxaparin and 120 unit/kg of dalteparin provide consistent reduction in anti-Xa levels and thus consistent anticoagulation. This is probably the reason that recent studies suggest LMWH is more effective for the treatment of patients with acute MI. In addition, because LMWH inhibits Xa activity predominantly, there is some suggestion that discontinuing it may be less problematic than is the case for UFH, which has fewer effects on Xa and more direct effects (when combined with antithrombin 3) on thrombin itself. The ability to use LMWH intravenously in the catheterization laboratory has not been a problem in regions where this strategy has been embraced.
Adverse Effects of Fibrinolytic Therapy
The most serious complication of treatment with thrombolytic agents is bleeding, particularly intracranial hemorrhage; however, catheter-based interventions substantially reduce this complication. The mechanism of bleeding with thrombolytic agents is unclear but has been related to the efficacy of the agent; the concomitant use of antithrombotic agents, such as heparin and aspirin; and the degree of hemostatic perturbation induced by the plasminogen activators. In most studies, the incidence of stroke and intracranial bleeding has been slightly higher with t-PA–type activators. This may be in keeping with the greater efficacy and rapidity of their effects. Although most bleeding occurs early during treatment, bleeding can occur 24–48 hours later, and vigilance even after the first few hours is important.
Intracranial bleeding is by far the most dangerous bleeding complication because it is often fatal. For most plasminogen activators, the incidence of intracranial hemorrhage is less than 1%, but it may be as high as 2–3% in elderly patients. Risk factors for intracranial bleeding include a history of cerebrovascular disease, hypertension, and age. These factors must be taken into account when determining whether a thrombolytic agent has an appropriate benefit-to-risk relationship. Changes in mental status require an immediate evaluation—clinical and computed tomography or magnetic resonance imaging. If bleeding is strongly suspected, heparin should be discontinued or neutralized with protamine.
There also is a substantial incidence of nonhemorrhagic, probably thrombotic, stroke that may be partly due to dissolution of thrombus within the heart, followed by migration. The exact mechanisms of this phenomenon are unclear. In some studies, the excess of strokes with t-PA has been found to be related to this phenomenon, and in other studies, it has been due to an apparent increase in intracranial bleeding.
Bleeding outside the brain can occur in any organ bed and should be prevented whenever possible. The puncture of noncompressible arterial or venous vessels is relatively contraindicated in all cardiovascular patients: those with unstable angina one day may be candidates for thrombolytic treatment on the next. Blood gas determinations should therefore be avoided if possible and oximeters used instead in cardiovascular patients. It should be understood that central lines placed in cardiovascular patients pose a substantial risk should there be a subsequent need for a lytic agent. Foley catheters and endotracheal (especially nasotracheal) intubation can also predispose to significant hemorrhage. Bleeding should be watched for assiduously. If severe bleeding occurs while heparin is in use, it should be antagonized with protamine. In general, this and supportive measures are all that can be done. In some studies, there appears to be a slightly higher incidence of extracranial bleeding with nonspecific activators than with t-PA; this finding has not been consistent. In an occasional patient, who begins to bleed shortly after receiving the plasminogen activator, aminocaproic acid, which changes the activation of plasminogen, may be useful. Otherwise, discontinuation of the drug and conservative local measures are all that can be done. If volume repletion is necessary, red blood cells are preferred to whole blood, and cryoprecipitate is preferred to fresh frozen plasma because it does not replenish plasminogen.
Allergic reactions related to the use of streptokinase are unusual but should be identified when they occur. Mild reactions, such as urticaria, can be treated with antihistamines; more severe reactions, such as bronchospasm, may require corticosteroids or epinephrine.
Bleeding after primary PCI can also be substantial, particularly if GP IIbIIIa agents are administered. The use of newer closure devices are touted by some clinicians, but close observation is the key to minimizing bleeding from the catheter site. On occasion, platelet transfusions may be necessary.
Antman EM, et al. 2007 Focused update of the ACC/AHA 2004 guidelines for the management of patients with ST-elevation myocardial infarction. J Am Coll Cardiol.
Jneid H, 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): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol.
Kushner FG, et al. 2009 Focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol
Sabatine MS, et al; CLARITY-TIMI 28 Investigators. Addition of clopidogrel
and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med.
Yusuf S, et al; Clopidogrel
in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel
in addition to aspirin
in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med.