An intravenous analgesic frequently administered to relieve chest pain associated with MI is

Pain can activate the sympathetic nervous system and cause diaphoresis, weakness, light-headedness, and palpitations in patients with myocardial infarction.

Myocardial infarction (MI) is a painful condition with tightness, pressure, or squeezing pain in the chest for approximately 75% of patients who experience it.

This pain often radiates to the arms, jaw, or back. Nitrates bring relief to many patients, but up to one-third of those who experience MI have nitrate-resistant chest pain and receive morphine instead.

Clinicians have used morphine for pain associated with MI since the early 1900s. The drug’s use through today is largely based on the “it’s always been done it this way” school of thought.

However, a 2005 observational study found that MI patients treated with morphine had inferior outcomes than those who didn’t receive morphine. More recently, researchers examined morphine’s use in MI in the June 2016 issue of American Heart Journal. In it, they acknowledged that the 2005 study was followed by a flurry of new questions and studies.

Although some concerns have been identified, few alternatives are available. Treating pain in MI patients is critical, as pain activates the sympathetic nervous system and causes or aggravates diaphoresis, weakness, light-headedness, and palpitations. This, in turn, increases cardiac work load.

As a potent opioid, morphine has seemed to be the ideal analgesic. It has innate hemodynamic effects that are beneficial during MI. It decreases heart rate, blood pressure, and venous return, and it may also stimulate local histamine-mediated processes. Theoretically, this reduces myocardial oxygen demand.

Meperidine causes similar hemodynamic effects, but possible central nervous system excitability or seizures have limited its use. Other opiates may also have harmful adverse effects in patients who have experienced MI. Meanwhile, morphine is associated with vomiting, hypotension, and respiratory depression.

The study authors also reported that morphine may inhibit and delay oral antiplatelet drug absorption. Rapid platelet inhibition is the cornerstone of treatment in acute coronary syndrome, and any slowing of antiplatelet effect may worsen outcomes.

Unfortunately, these adverse effects are unsubstantiated by prospective, randomized outcomes trials. Although further research is needed, study design will be difficult to structure because of ethical limitations associated with placebo-controlled randomization.

The study authors summarized alternatives to morphine, including acetaminophen for pain measuring less than 7 on a visual analogue scale; alfentanil, which has some limitations; and drugs in the naloxone, naloxagol, and methylnaltrexone family.

The researchers concluded that morphine remains a valuable agent when nitrates, beta-blockers, and expedited reperfusion fail to relieve pain.

Approach Considerations

Morbidity and mortality from myocardial infarction are significantly reduced if patients and bystanders recognize symptoms early, activate the emergency medical service (EMS) system, and thereby shorten the time to definitive treatment. Trained prehospital personnel can provide life-saving interventions if the patient develops cardiac arrest.

The key to improved survival is the availability of early defibrillation. Approximately 1 in every 300 patients with chest pain transported to the ED by private vehicle goes into cardiac arrest en route. Several studies have confirmed that patients with STEMI usually do not call 911; in one study, only 23% of patients with a confirmed coronary event used EMS.

The first goal for healthcare professionals is to diagnose in a very rapid manner whether the patient is having an STEMI or NSTEMI because therapy differs between the 2 types of myocardial infarction. Particular considerations and differences involve the urgency of therapy and degree of evidence regarding different pharmacological options.

As a general rule, initial therapy for acute myocardial infarction is directed toward restoration of perfusion as soon as possible to salvage as much of the jeopardized myocardium as possible. This may be accomplished through medical or mechanical means, such as PCI or CABG.

Further treatment is based on the following:

• Restoration of the balance between the oxygen supply and demand to prevent further ischemia

• Pain relief

• Prevention and treatment of any complications that may arise

Coronary collateral circulation

The coronary collateral circulation is an important factor in terms of the amount of damage to the myocardium that results from coronary occlusion. Well-developed collaterals may greatly limit or even completely eliminate myocardial infarction despite complete occlusion of a coronary artery.

Reports vary as to the number of patients who have collaterals at the time of a myocardial infarction; many patients develop collaterals in the hours and days after an occlusion occurs. [46] When the patient is at rest, blood flow through collaterals is normal, a fact that accounts for the absence of resting ischemia. However, blood flow through collaterals does not increase with exercise; this inability accounts for the occurrence of ischemia during periods of stress. [47]

Prehospital Care

All patients being transported for chest pain should be managed as if the pain were ischemic in origin, unless clear evidence to the contrary is established. If available, an advanced life support (ALS) unit should transport patients with hemodynamic instability or respiratory difficulty.

Prehospital notification by Emergency Medical Services (EMS) personnel should alert ED staff to the possibility of a patient with myocardial infarction. EMS personnel should receive online medical advice for a patient with high-risk presentation.

The AHA protocol can be adopted for use by prehospital emergency personnel. This protocol recommends empiric treatment of patients with suspected STEMI with morphine, oxygen, nitroglycerin, and aspirin.

Specific prehospital care includes the following:

• Intravenous access, supplemental oxygen, pulse oximetry

• Immediate administration of aspirin en route

• Nitroglycerin for active chest pain, given sublingually or by spray

• Telemetry and prehospital ECG, if available

Most deaths caused by myocardial infarction occur early and are attributable to primary ventricular fibrillation (VF). Therefore, initial objectives are immediate electrocardiographic monitoring; electric cardioversion of VF, should it occur; and rapid transfer of the patient to facilitate prompt coronary recanalization. The effectiveness of rapid response by rescuers (eg, police and firefighters) trained in defibrillation have been conclusively documented in community-based systems in Belfast, Ireland; Columbus, Ohio; Los Angeles, California; and Seattle, Washington.

Approximately 65% of deaths caused by myocardial infarction occur in the first hour. More than 60% of these deaths (ie, 39% of patients who would otherwise die) may be prevented with defibrillation by a bystander or a first-responding rescuer.

Additional objectives of prehospital care by paramedical and emergency personnel include adequate analgesia (generally achieved with morphine); pharmacologic reduction of excessive sympathoadrenal and vagal stimulation; treatment of hemodynamically significant or symptomatic ventricular arrhythmias (generally with lidocaine); and support of cardiac output, systemic blood pressure, and respiration.

The AHA published a statement on integrating prehospital ECGs into care for patients with ACS (see AHA Publishes Statement on Integrating Prehospital ECGs Into Care for ACS Patients). Prehospital integration of ECG interpretation has been shown to decrease "door to balloon time," to allow paramedics to bypass non-PCI hospitals in favor of better-equipped facilities and to expedite care by allowing an emergency physician to activate the catheterization laboratory before patient arrival.

Prehospital administration of tissue-type plasminogen activator (t-PA), aspirin, and heparin may be given to patients with bona fide myocardial infarction by paramedics, as guided by electrocardiographic findings, within 90 minutes of the onset of symptoms. This treatment improves outcomes, as compared with thrombolysis begun after the patient arrives at the hospital.

Atropine, 0.5 mg given intravenously at 5-minute intervals to a maximum of 2-4 mg, is useful to counteract excessive vagal tone that often underlies bradyarrhythmias and hypotension. If bradycardia persists, transthoracic pacing may be life saving.

Timely reperfusion therapy has shown that the long-term mortality rate in patients with STEMI is 15.4% when the system delay (time from first contact with health care system to the initiation of reperfusion therapy) is 60 minutes or less. The long-term mortality doubles to a rate of 30.8% when the system delay is more than 180 minutes. [48]

In experimental models of MI, erythropoietin reduces infarct size and improves left ventricular (LV) function. However, the Reduction of Infarct Expansion and Ventricular Remodeling With Erythropoietin After Large Myocardial Infarction (REVEAL) trial evaluated the safety and efficacy of a single intravenous bolus of epoetin alfa in patients with STEMI who had successful reperfusion with primary or rescue PCI. [49] A single intravenous bolus of epoetin alfa within 4 hours of PCI did not reduce infarct size and was associated with higher rates of adverse cardiovascular events.

Emergency Department Care

For purposes of determining appropriate emergency treatment, viewing myocardial infarction as part of a spectrum of coronary syndromes is helpful; this spectrum includes the following:

• STEMI

• NSTEMI

• Unstable angina

Treatment is aimed at the following:

• Restoration of the balance between the oxygen supply and demand to prevent further ischemia

• Pain relief

• Prevention and treatment of complications

Treatment in the ED begins with focused cardiovascular history–taking and physical examination, the establishment of intravenous (IV) access, the use of 12-lead ECG (see the image below), and continuous rhythm monitoring. All patients with suspected myocardial infarction should be given chewable aspirin, 160-325 mg, unless they have a documented allergy to aspirin.

Pulse oximetry should be performed, and appropriate supplemental oxygen should be given (maintain oxygen saturation >90%) to prevent hypoxemia. High concentrations may be counterproductive because of vasoconstriction and the lack of augmented myocardial oxygen delivery in normoxemic patients.

Note that supplemental oxygen may harm nonhypoxic patients with STEMI, increasing the risk of myocardial injury, recurrent myocardial infarction, and major cardiac arrhythmia, according to results of the randomized, controlled, multicenter Air Versus Oxygen in ST-Elevation Myocardial Infarction (AVOID) study. [50] The trial involved patients with STEMI who had normal oxygen levels (ie, oxygen saturation levels of more than 94%), with the patients randomized into two groups: those who received supplemental oxygen (218 patients) and those who were given no supplemental oxygen (223 patients) unless their oxygen saturation level fell below 94%. [50]

A 25% rise in creatine kinase, suggesting increased myocardial injury, was observed at the primary endpoint in the supplemental oxygen group. Primary endpoint results for troponin I, however, did not differ significantly between the two groups. It was also found that both groups had a similar mortality rate (although the study did not have enough power to examine major adverse cardiac events). However, the rates of MI recurrence and significant arrhythmia were significantly higher in the supplemental oxygen group, but these differences were no longer significant at 6 months. [50]

A chest radiograph should be obtained soon after arrival, to screen for alternative causes of chest pain and to identify possible contraindications to thrombolysis (eg, aortic dissection).

Initial stabilization of patients with suspected myocardial infarction and ongoing acute chest pain should include administration of sublingual nitroglycerin; if pain persists, 2 additional doses of nitroglycerin may be administered at 5-minute intervals. Patients should be free of contraindications, such as hypotension (systolic blood pressure < 90 mm Hg), bradycardia, tachycardia, or findings suggestive of right ventricle [RV] infarction.

Refractory or severe pain should be treated symptomatically with IV morphine, meperidine, or pentazocine. Doses of morphine, 4-8 mg IV, may be repeated every 5-15 minutes with relative impunity until the pain is relieved or toxicity is manifested by hypotension, vomiting, or depressed respiration. Should toxicity occur, a morphine antagonist, such as naloxone, may reverse it. The patient's blood pressure and pulse must be monitored; the systolic blood pressure must be maintained above 100 mm Hg and, optimally, below 140 mm Hg.

Relative hypotension may be treated by elevating the lower extremities or by giving fluids, except in patients with concomitant pulmonary congestion, in whom treatment for cardiogenic shock may be required. Atropine, in doses similar to those given in the prehospital phase, may increase blood pressure if hypotension reflects bradycardia or excess vagal tone.

Some EDs practice ambulance diversion, wherein the ED is temporarily closed to ambulance traffic. [51] This practice has been associated with increased 30-day, 90-day, 9-month, and 1-year mortality among patients using Medicare who experienced acute myocardial infarction. Although confined to California, this study by Shen et al shows the importance between ED care and the survival of patients experiencing acute myocardial infarction.

Treatment of patients with STEMI

The initial focus in the ED should be on identifying patients with STEMI. An ECG should be performed and shown to an experienced emergency medicine physician within 10 minutes of ED arrival. The 2013 guidelines from the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) for the management of patients with STEMI recommend ECGs be done in the field by ambulance personnel to facilitate more rapid triage and quicker treatment. [52, 53]

If STEMI is present, the decision as to whether the patient will be treated with thrombolysis or primary PCI should be made within the next 10 minutes. Treatment options include the immediate start of IV thrombolysis in the ED or the immediate transfer of the patient to the cardiac catheterization laboratory for primary percutaneous transluminal coronary angioplasty (PTCA). [2, 3] The goal for patients with STEMI should be to achieve a door-to-drug time of within 30 minutes and a door-to-balloon time of within 90 minutes.

In patients with STEMI who are to be treated with primary PCI, delays in administering the procedure are associated with higher mortality in these patients, according to a study by Rathore et al. [54] In a prospective cohort study of 43,801 patients enrolled in the American College of Cardiology National Cardiovascular Data Registry, 2005-2006, longer door-to-balloon times were associated with a higher adjusted risk of in-hospital mortality, in a continuous, nonlinear fashion (30 min = 3%, 60 min = 3.5%, 90 min = 4.3%, 120 min = 5.6%, 150 min = 7%, 180 min = 8.4%). A reduction in door-to-balloon time from 90 minutes to 60 minutes was associated with 0.8% lower mortality, and a reduction from 60 minutes to 30 minutes was associated with a 0.5% lower mortality.

Delays in the administration of thrombolysis often occur because of the following factors:

• Delay in obtaining an ECG

• Interpretation

• Lack of immediate availability of thrombolytic agents

• Outdated protocols requiring cardiology consultation before thrombolytic treatment

The AHA recommends the initiation of beta-blockers to all patients with STEMI (unless beta-blockers are contraindicated). Sinert et al reviewed records from 1966 to August 2009 to determine the efficacy of treating STEMI patients with beta-blockers within the first 24 hours. They found a single randomized trial that met inclusion criteria. This trial demonstrated that beta-blocker treatment within 24 hours in patients presenting with STEMI followed by standardized care on day 2 or 3 did not reduce mortality or reinfarction when compared with placebo or no immediate treatment followed by standardized care. [55]

A separate study by Brinkman et al also suggests that although a rationale for the use of beta-blockers prior to surgery has been reported, the use of these drugs should be considered on an individual basis. Because no differences in mortality or morbidity were found, the findings did not support preoperative beta-blockade as a useful quality indicator for coronary artery bypass graft surgery. [56]

In a placebo-controlled, multicenter trial of 240 STEMI (ST-segment elevation myocardial infarction) patients treated with percutaneous coronary intervention (PCI) and thrombus aspiration, the additional intracoronary administration of adenosine, but not nitroprusside, significantly improved microvascular obstruction (MVO). ST-segment resolution >70% on surface electrocardiogram at 90 minutes after PCI occurred in 71% of patients treated with adenosine, 54% of those treated with nitroprusside, and 51% of those who received saline. Angiographic MVO occurred in 18% of the adenosine group, 24% of the nitroprusside group, and 30% of the placebo group. Major adverse cardiac events were observed in 10%, 14%, and 20% of these groups, respectively. [57]

Treatment of patients with NSTEMI

If STEMI is not present, then the workup should proceed looking for unstable angina or NSTEMI and for alternative diagnoses. Confirmation of the diagnosis of NSTEMI requires waiting for the results of cardiac markers.

Point-of-care (POC) assays are common in the ED setting but have lower negative predictive values compared with laboratory assays. The current POC cardiac troponin I (cTnI) assays are less sensitive for outcome prediction among patients with myocardial injury. [58] Clinical judgment and decision-making for the patient with suspected acute coronary syndrome (ACS) should not rely solely on POC assay results. If a clinical suspicion of myocardial infarction remains despite negative cTnI results with the POC assays, those results should be complemented by results from more sensitive laboratory assays.

In the case of unstable angina, diagnosis may await further diagnostic studies, such as coronary angiography or imaging studies, to confirm the diagnosis and to distinguish it from noncoronary causes of chest pain. Although patients presenting with no ST-segment elevation are not candidates for immediate treatment with thrombolytic agents, they should receive anti-ischemic therapy and may be candidates for PCI urgently or during admission.

Low-risk patients

Low-risk patients without obvious ischemia should be observed and monitored in either a step-down care unit or an intermediate care unit to evaluate or observe for chest pain.

Concordance of ED management of AMI

A study by Tsai et al determined that overall ED concordance with ACC/AHA guideline recommendations for management of AMI is low to moderate. Emergency physicians should continue to develop strategies with emergency medical services and cardiologists to improve the care process. [59]

In-Hospital Treatment

Critical care units (CCUs) have reduced early mortality rates from acute myocardial infarction by approximately 50% by providing immediate defibrillation and by facilitating the implementation of beneficial interventions. These interventions include the administration of IV medications and therapy designed to do the following:

• Limit the extent of myocardial infarction

• To salvage jeopardized ischemic myocardium

• Recanalize infarct-related arteries.

The diagnose and treatment of other conditions is useful as well. [60] Alternatives for coronary recanalization include the IV administration of thrombolytic agents and catheter-based approaches. [3]

General measures commonly include the use of stool softeners to prevent constipation, straining, and consequent circulatory derangements.

Prophylaxis for stress ulcers with oral sucralfate, 1 g given twice a day, or an H2-antagonist (famotidine, ranitidine, or cimetidine), given orally or intravenously at 6- to 12-hour intervals, is appropriate for patients at high risk, including those with sepsis, hypotension or shock, bleeding diathesis, or elevated intracranial pressure or who have a requirement for prolonged mechanical intervention.

Antipyretics (eg, acetaminophen) should be used to prevent or suppress the fever that is typically seen in the first 24-48 hours and its consequent tachycardia. Patients with uncomplicated myocardial infarction need be confined to bed for only 1 day.

Physical activity should be limited (bed-chair regimen) throughout the patient's CCU stay, with gradual and carefully monitored resumption of ambulatory activity in the late hospital phase. Educational programs targeting smoking cessation, lipid lowering, and treatment of hypertension, as indicated, in addition to phased rehabilitation programs, should be started early during the hospital course for patients with uncomplicated myocardial infarction. Use of sedative, anxiolytic, and hypnotic drugs at night may be helpful. Also important are optimal communication with compassionate physicians and nurses and the reassurance it provides.

Preventive therapy in the acute hospital phase

Beta-adrenergic blockers are of benefit when given intravenously within 4 hours of the onset of pain and continued on a long-term basis. Mortality, sudden death, and infarct size are reduced in patients with Q-wave myocardial infarction when beta-blockers are given early. Patients with unstable angina also benefit through a reduction in the incidence or severity of myocardial infarction. Metoprolol or atenolol are commonly used.

Chewing an aspirin shortly after onset of chest pain is a ready means to inhibit thrombosis. In the hospital, small trials indicate benefits (decreased size of infarcts and mortality) from insulin infusion, along with glucose and potassium, presumably through an anti-apoptotic effect.

Patients with insulin-dependent diabetes mellitus and peripheral vascular disease may be treated with caution; the benefit of angioplasty is decreased in these patients.

ACE inhibitors are useful for long-term therapy and also appear to benefit patients who have no evidence of hypotension if administration is begun within the first 24 hours after the onset of myocardial infarction. Alternatives include captopril, 12.5-50 mg given orally twice a day; enalapril, 5-40 mg given orally daily or twice a day; or any of the newer agents (eg, lisinopril, quinapril, or ramipril), given in pharmacologically equivalent doses.

Treatment with both beta-adrenergic blockers and ACE inhibitors may improve the balance between myocardial oxygen supply and demand, and it may limit infarct size. Appropriate treatment of fluid status to optimize left ventricular filling pressures, maintain oxygen saturation, and control heart rate by avoiding reflex sympathoadrenal stimulation is also beneficial.

Calcium channel blockers have not been beneficial in acute myocardial infarction, and they may exert deleterious adverse effects alone or when given with other medications. Therefore, they should generally be avoided. Diltiazem may be useful for rate control in patients with atrial fibrillation. Verapamil may be useful in patients with obstructive hypertrophy.

Continuing chest pain suggestive of ischemia is an indication for cardiac catheterization and revascularization (PTCA or surgery). The decision to proceed and the choice of modality are largely made on the basis of the results of angiography and an assessment of ventricular function. IV nitroglycerin, titrated to 10-200 mcg/min to prevent hypotension, may alleviate coronary artery spasm and postinfarct angina by reducing arterial resistance and ventricular afterload. Dosages higher than this diminish systemic venous tone and blood pressure, potentially (paradoxically) exacerbating ischemia.

Diminished afterload and preload and decreased LVEDP probably mediate the favorable effects, facilitating myocardial perfusion. Tolerance to continuously administered IV nitrates occurs rapidly, often within hours.

Thrombolytic Therapy

Thrombolytic therapy has been shown to improve survival rates in ST-segment elevation myocardial infarction but is not indicated in the treatment for non–ST-segment elevation myocardial infarction. Door-to-drug time should be no more than 30 minutes. [61] Thrombolytic therapy administered within the first 2 hours can occasionally abort myocardial infarction and dramatically reduce the mortality rate.

Thrombolysis is generally preferred to PCI in cases where the time from symptom onset is less than 3 hours and if there would be a delay to PCI, greater than 1-2 additional hours to door-to-balloon time. A detailed list of contraindications and cautions for the use of fibrinolytic therapy is shown in Table 12 of the ACC/AHA Guidelines for the Management of Patients With ST-Elevation Myocardial Infarction—Executive Summary.

Thrombolytic treatment may be helpful in some patients, particularly those with stuttering infarcts, who are first seen 6-12 hours after the onset of symptoms. It has not been demonstrated to be effective in patients with non-Q-wave myocardial infarction or unstable angina. The clinical effectiveness of coronary thrombolysis depends on the frequency, rapidity, and persistence of recanalization. All of these factors depend not only on the intensity of fibrinolysis [62] but also on the inhibition of coagulation and platelet-induced thrombosis, which undoubtedly occur concomitantly.

In general, use of thrombolytic agents has been well demonstrated to be effective in patients aged 75 years or younger who present with suspected Q-wave myocardial infarction within 6 hours after the onset of symptoms and in whom contraindications are not present. Although the absolute risk of complications is greatest in the elderly, overall mortality reduction is at least as great in this group as in others, because the prognosis for patients with myocardial infarction that is managed conservatively is also worse for elderly patients than it is for younger patients.

Fibrinolytic agents

The first generation of fibrinolytic drugs (eg, streptokinase, urokinase, acetylated plasminogen streptokinase activator complexes [APSACs], reteplase, and novel plasminogen activator [n-PA]) indiscriminately induce activation of circulating plasminogen and clot-associated plasminogen. First-generation drugs invariably elicit a systemic lytic state characterized by depletion of circulating fibrinogen, plasminogen, and hemostatic proteins and by marked elevation of concentrations of fibrinogen degradation products in plasma.

Second-generation drugs (eg, t-PA, single-chain urokinase plasminogen activator), including agents such as tenecteplase, preferentially activate plasminogen in the fibrin domain, rather than in the circulation, as with free plasminogen. Therefore, these drugs have clot selectivity. Tenecteplase should be initiated as soon as possible after the onset of acute myocardial infarction (AMI) symptoms. In AMI patients, tenecteplase administered as a single bolus exhibits a biphasic disposition from the plasma.

In optimal regimens, these agents induce clot lysis without inducing a systemic lytic state, they are less prone than nonselective agents to predispose the patient to hemorrhage necessitating transfusion, and they are effective in inducing recanalization in 80-90% of infarct-related arteries within 90 minutes. Therefore, t-PA recanalizes 75-80% of infarct-related arteries; by contrast, IV streptokinase recanalizes approximately 50% of infarct-related arteries.

Coronary thrombolysis with IV activators of plasminogen improves ventricular function and decreases mortality, especially early after myocardial infarction and when initiated a few hours after the onset of ischemia. Even when started late (6 hours or more after the onset of myocardial infarction), restored patency of the infarct-related artery may confer an early mortality benefit, perhaps because of improved collateral blood flow and ventricular remodeling and function or decreased infarct expansion, arrhythmogenicity, ventricular aneurysm formation, and late arrhythmia associated with aneurysms that do develop.

In the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) trial, second-generation agents significantly improved 24-hour, 30-day, and 1-year mortality rates, as well as the rate of survival without disabling stroke. [63, 64, 65]

Plasminogen activators should not be given to patients with active internal bleeding or a bleeding diathesis; with suspected aortic dissection; who have undergone recent trauma; who have intracranial neoplasm; or who are in hypertensive crisis. Relative contraindications include prolonged or traumatic cardiopulmonary resuscitation, peptic ulcer disease, remote cerebrovascular accident, and hepatic failure. Safety has not been established for pregnant women, although safety has been established for menstruating women.

Pitfalls of coronary thrombolysis

The risks of coronary thrombolysis include bleeding, much of which is confined to sites of vascular access. [66] Marked depletion of fibrinogen or prolongation of the bleeding time may be markers of pharmacologic effects that lead to bleeding. With thrombolysis, the incidence of hemorrhagic stroke is increased, but the risk of thrombotic or embolic stroke is somewhat reduced; overall, any small increase in fatal cerebrovascular accidents is more than offset by the favorable effect on survival.

Even optimally effective coronary thrombolysis is compromised by early thrombotic reocclusion in 6-20% of patients with initial recanalization, unless vigorous conjunctive anticoagulation is started immediately.

Thrombolytic agents and mechanical revascularization

Use of thrombolytic medications and mechanical revascularization may be required. In individuals in whom fibrinolytic therapy fails to successfully recanalize the infarct-related artery (defined by ST-segment resolution < 50% at 90 min), a rescue PCI can be performed. Rescue PCI should be performed in individuals who are younger than 75 years and suitable for revascularization, if, after thrombolysis, they have evidence of acute pulmonary edema, cardiogenic shock, or hemodynamically unstable ventricular arrhythmias. Diagnostic coronary angiography post thrombolysis may be performed; however, further studies are needed to clarify the role and benefit of routine PCI to the infarct-related artery in asymptomatic patients who demonstrate successful thrombolysis.

The Occluded Artery Trial (OAT) determined that PCI to a persistently occluded infarct-related artery greater than 24 hours after onset of STEMI is not currently recommended per the latest guidelines. Facilitated PCI with thrombolysis is also not recommended in the guidelines because this approach may be harmful. Facilitated PCI refers to giving thrombolysis immediately prior to planned urgent PCI. [61]

CABG may be needed for patients whose condition fails to respond to PCI with stenting; if necessary, CABG is feasible even after the administration of IV thrombolytic agents. Despite a high perioperative mortality rate for CABG within 24 hours of failed pharmacologic thrombolysis or PCI, subsequent 1-year mortality among survivors may be as low as 2% and is not different from the rate in patients who survive CABG performed late after myocardial infarction. CABG is an option for patients in whom other efforts to establish reperfusion fail and who have ongoing major complications. Contrary to initial expectations, not all patients treated with thrombolytic drugs need early cardiac catheterization and angioplasty.

Antithrombotic Agents

At present, IV unfractionated heparin (UFH) is routinely administered, in addition to orally administered aspirin. Alternatives include low-molecular-weight heparin (LMWH or enoxaparin), other inhibitors of coagulation (eg, hirudin, fondaparinux, bivalirudin), and antagonists of binding of fibrinogen to the platelet surface glycoprotein IIb/IIIa (GPIIb/IIIa) receptor (eg, abciximab, eptifibatide, tirofiban, orbofiban). Thienopyridines (eg, ticlopidine, clopidogrel) similarly inhibit platelet aggregation by binding to platelet adenosine diphosphate receptors, which block activation of the IIb/IIIa pathway.

Anticoagulation therapy

In the management of all patients with ACS or suspected ACS, anticoagulation therapy is the standard of care. In patients with or suspected unstable angina (UA)/NSTEMI, anticoagulation therapy should be added to antiplatelet therapy as soon as possible. In patients who have been selected to undergo an early invasive strategy for UA/NSTEMI, proven effective anticoagulant therapy includes UFH, enoxaparin, fondaparinux, and bivalirudin.

Patients in whom conservative management is initially deemed appropriate should be given the same anticoagulation options, with the exception of bivalirudin, for which data are limited. Fondaparinux is preferred in individuals with an increased bleeding risk and in whom conservative management is selected. In initial conservative therapy, both enoxaparin and fondaparinux may be preferable over UFH, unless CABG is contemplated within the first 24 hours. [28]

In UA/NSTEMI, the duration of anticoagulation in uncomplicated conservative therapy is 48 hours for UFH and the entire hospital stay is up to 8 days for LMWH or fondaparinux. In patients for whom CABG is chosen for revascularization, continue UFH up to the time of surgery, discontinue LMWH/fondaparinux 24 hours before surgery, and switch to UFH; alternatively, discontinue bivalirudin 3 hours before surgery and switch to UFH. If PCI is performed, anticoagulation therapy can be discontinued safely post successful revascularization. [28]

In STEMI, parenteral anticoagulant therapy with UFH or bivalirudin is a Class I indication in patients undergoing primary PCI. [61, 67] Data are scant with regard to heparin efficacy in patients not receiving thrombolytic therapy in the setting of myocardial infarction; however, considerable rationale exists for ancillary heparin therapy to inhibit the coagulation cascade.

The ATOLL trial’s findings suggest that 0.5 mg/kg of intravenous enoxaparin significantly reduced clinical ischemic outcomes compared with unfractionated heparin without differences in bleeding and procedural success in patients presenting with ST-elevation myocardial infarction. [68]

LMWH is commonly used because of convenient dosing, reliable therapeutic levels, and decreased incidence of heparin-induced-thrombocytopenia, especially if anticipated use is greater than 2-3 days. Assuming that a patient does not have significant renal dysfunction (serum creatinine level >2.5 mg/dL in men or >2 mg/dL in women),LMWH may be used with caution as an alternative to UFH as an ancillary therapy to fibrinolytic agents, regardless of age (note that different loading and maintenance doses are used in patients aged >75 y). [61]

As of the 2009 focused updates, the ACC/AHA STEMI and PCI guidelines permit bivalirudin as an alternative to UFH for parenteral anticoagulant therapy. Bivalirudin, a direct thrombin inhibitor, should be combined with high-dose clopidogrel load. It is recommended as reasonable anticoagulation for patients with high bleeding risk. [67]

In the final report of the HORIZONS-AMI trial, which assessed the 3-year outcomes of effectiveness and safety for bivalirudin monotherapy and paclitaxel-eluting stenting, outcomes were sustained for patients with STEMI undergoing primary PCI. [69]

Anticoagulation and Thrombolytic Therapy in STEMI

In the previous 2004 guidelines on STEMI management, patients treated with fibrinolytic therapy were recommended for heparin therapy depending on the fibrinolytic agent used. [70] In the 2007 STEMI-focused update, heparin has an established role as an adjunctive agent in patients receiving both selective and nonselective fibrinolytic therapy, with a class I indication. [61]

Although no new trials specifically focused on UFH in STEMI were performed, a number of new alternative anticoagulant therapy trials in STEMI compared the anticoagulant drug to UFH and to placebo. Given these results, the group found adjunctive anticoagulant therapy to be beneficial in STEMI. For patients receiving thrombolysis in STEMI, the proven anticoagulant adjuncts include UFH, enoxaparin, and fondaparinux.

The duration of therapy with anticoagulants should be at least 48 hour and up to 8 days. If PCI is to be performed, fondaparinux as a sole anticoagulant should not be used secondary to higher rates of catheter thrombosis during the procedure. [61] Another anticoagulant with antifactor IIa should be used to support the procedure.

Aspirin and Antiplatelet Therapy

Clopidogrel

Aspirin should be administered immediately if not already taken by the patient at home or administered by EMS before arrival. Use clopidogrel (Plavix) in case of aspirin allergy. Data from the CLARITY trial (CLopidogrel as Adjunctive Reperfusion Therapy Thrombolysis in Myocardial Infarction [TIMI] 28) suggest that adding clopidogrel to this regimen is safe and effective. [71] The clopidogrel dose used was 300 mg. Further studies suggest that a higher dose of clopidogrel may have added benefit. [72]

The Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty-Myocardial Infarction (ARMYDA-6 MI) multicenter study demonstrated that in patients with STEMI, a loading dose of 600 mg clopidogrel prior to primary PCI was associated with a smaller infarct size when compared with a 300-mg loading dose. [73]

Clopidogrel use along with aspirin and anticoagulation therapy has a class I indication for the entire spectrum of acute coronary syndromes. In the ACC/AHA STEMI 2007 updated guidelines, clopidogrel at 75 mg/d should be given regardless of reperfusion therapy and should be given for at least 14 days. It is reasonable to administer a loading dose of 300 mg initially and continue this regimen long term (eg, 1 y). [61]

In the ACC/AHA UA/NSTEMI 2012 guidelines, clopidogrel should be prescribed at 75 mg/d for patients treated medically or with a bare metal stent, for a duration of at least 1 month and, ideally, up to 1 year. For patients treated with a drug-eluting stent (DES), clopidogrel needs to be continued for at least 1 year. [28] If CABG is planned, clopidogrel should be withheld 5-7 days prior to the procedure, unless the urgency of the procedure outweighs the bleeding risk. [28, 61]

In patients receiving dual antiplatelet therapy (aspirin and clopidogrel), the prophylactic use of proton pump inhibitors may reduce the rate of upper gastrointestinal bleeding. [74]  However, a study by Charlot et al found that patients treated with aspirin for first-time MI have an increased risk of adverse cardiovascular events if used in combination with PPIs. [75]  The response to clopidogrel varies among patients, and diminished responsiveness to clopidogrel has been observed. Clopidogrel is a prodrug and requires conversion to R130964, its active metabolite, through a 2-step process in the liver that involves the CYP2C19 isoenzyme. Patients who possess the genetic variants of the CYP2C19 allele or drugs (eg, omeprazole) that may inhibit the effect of CYP2C19 may decrease the conversion to the active metabolite. [28] For more information see Clopidogrel Dosing and CYP2C19.

Ticagrelor

Ticagrelor is indicated to reduce the rate of thrombotic CV events following ACS. This agent also reduces the rate of stent thrombosis in patients who have undergone stent placement for treatment of ACS. Ticagrelor is used in addition to low-dose aspirin (75-100 mg/day). [28]

In September 2015, the indication for ticagrelor was expanded to include use in patients with a history of MI more than 1 year previously. [76] Approval was based on the PEGASUS TIMI-54 study, a large-scale outcomes trial involving over 21,000 patients. PEGASUS TIMI-54 investigated ticagrelor 60 mg twice daily plus low-dose aspirin, compared to placebo plus low-dose aspirin, for the long-term prevention of CV death, heart attack, and stroke in patients who had experienced an MI 1-3 years prior to study enrollment. In patients with an MI longer than 1 year previously, treatment with ticagrelor significantly reduced the risk of CV death, MI, or stroke compared with placebo (P=0.004). [77]

Timing of clopidogrel initiation in UA/NSTEMI

Timing of clopidogrel initiation has generally fallen into 2 strategies: (1) starting as soon as possible or (2) delaying treatment until diagnostic angiography has been performed to evaluate the extent of coronary disease. In the latter strategy, if PCI is indicated, then the drug is administered “on the table.” This strategy loses the upstream benefits of reducing early ischemia; however, it minimizes the risk of major bleeding should the patient require CABG.

The ACC/AHA 2012 UA/NSTEMI guidelines describe subtle differences in the recommendation for the timing of clopidogrel initiation, depending on whether an initial conservative or invasive strategy is chosen. [28] For an initial invasive strategy, the guidelines give a class I indication to the choice of either upstream (before diagnostic angiography) clopidogrel with a loading dose or upstream intravenous glycoprotein IIb/IIIa inhibitor.

In fact, the guidelines also state that it is reasonable to consider use of both agents upstream concomitantly. In an initial conservative strategy, clopidogrel therapy with a loading dose should be added as soon as possible to anticoagulation therapy and aspirin and should be given for at least 1 month and, ideally, up to 1 year. Should the patient develop recurrent symptoms, hemodynamic instability, or acute heart failure, diagnostic angiography should be performed and management recommendation changes on upstream therapy should be the same as early invasive therapy. [28]

Aspirin use in primary prevention

Low-dose aspirin has shown substantial benefit for primary prevention of myocardial infarction and stroke, but its use must be weighed against the risk for hemorrhagic stroke and gastrointestinal bleeding.

In one study, aspirin was associated with significant reduction (12% proportional reduction) for serious vascular events (0.51% aspirin vs 0.57% control annually), but the net effect on stroke was not significant. The Antithrombotic Trialists’ (ATT) Collaboration conducted meta-analyses of serious vascular events, including myocardial infarction, stroke, and vascular death, and major bleeds in 6 primary prevention trials and in 16 secondary prevention trials that compared long-term aspirin versus control. The primary prevention trials included 95,000 individuals at low-average risk, and the secondary prevention trials included 17,000 individuals at high-average risk. [78]

The reduction in vascular events recorded in the study was largely accounted for by a 20% reduction in nonfatal myocardial infarction (0.18% vs 0.23% annually). [78] Aspirin increased risk for major gastrointestinal and extracranial bleeding. The use of aspirin for primary prevention must be advised in context with the patient’s personal risks and history.

In a systematic review of randomized, case-control, and cohort studies, Cuzick et al found that regular use of aspirin (dose range, 75-325 mg/day) for 3 years lowered the risk for MI, stroke, cancer, and premature death in average-risk adults aged 50-65 years in the general population. [79] In the adults who took prophylactic aspirin for at least 10 years, there was a reduction in relative risk for MI, stroke, and cancer events over a 15-year period that ranged between 7% for women and 9% for men. [79, 80] Moreover, aspirin use over a 20-year period had an overall 4% relative reduction in all deaths. However, higher aspirin doses did not increase the benefits associated with long-term use, and the risk of adverse events (eg, hemorrhage) increased with higher doses. [79, 80]

On September 8, 2015, the U.S. Food and Drug Administration (FDA) approved DURLAZA (aspirin), the first and only 24-hour, Extended Release Capsules, (162.5mg) for theprevention of stroke and acute cardiac events, including myocardial infarction.

Before initiating daily aspirin use, all patients should consult with their health-care providers to discuss potential serious adverse effects, including the risk of bleeding. [80]

Glycoprotein IIb/IIIa receptor inhibitors

In patients with unstable angina or NSTEMI, administer a platelet glycoprotein (GP) IIb/IIIa receptor antagonist, in addition to aspirin and anticoagulation therapy, to those with continuing ischemia or with other high-risk features and to patients in whom a PCI is planned. Eptifibatide and tirofiban are approved for this use. Abciximab [81, 82] also can be used for 12-24 hours in patients with unstable angina or NSTEMI in whom a PCI is planned within the next 24 hours.

In general, the ACC/AHA 2007 UA/NSTEMI guidelines recommend using upstream GP IIb/IIIa receptor inhibitors if PCI is to be performed post diagnostic angiography or as part of an invasive strategy. They also specifically note that abciximab is not recommended for use in patients not planning to undergo PCI.

In an initial early conservative strategy in which diagnostic angiography or stress testing will not be performed or in which findings are negative, it is recommended to stop this therapy if it has been started. Additionally, discontinue GPIIb/IIIa inhibitors if it has been determined the patient will undergo medical therapy.

If CABG is the choice of revascularization, discontinue tirofiban or eptifibatide 4 hours prior to surgery. If bivalirudin was administered as an anticoagulant and clopidogrel was given as a loading dose at least 6 hours prior to PCI, it is reasonable to omit usage of a GP IIb/IIIa inhibitor. [28]

In STEMI, data for usage of GP IIb/IIIa antagonists is available. As of the 2009 focused updates to the ACC/AHA STEMI guidelines, tirofiban and eptifibatide as well as abciximab have a class IIa recommendation for consideration at the time of primary PCI. The efficacy of GP IIb/IIIa inhibitors in preparation of patients with STEMI before angiography and PCI is not certain. [67]

Additional Medical Therapy

Morphine sulfate

Morphine sulfate may be administered to relieve pain and anxiety. This is the analgesic of choice for anginal pain relief in STEMI. [61] For unstable angina and NSTEMI, barring contraindications, it is reasonable to administer morphine sulfate if the patient has refractory chest discomfort despite nitroglycerin use. [28]

Nitrates

Nitrates are useful for preload reduction and symptomatic relief but have no apparent impact on mortality rate in myocardial infarction. Systolic BP < 90, HR < 60 or >100, and right ventricular infarction are contraindications to nitrate use. IV nitroglycerin is indicated for relief of ongoing ischemic discomfort, control of hypertension, or management of pulmonary congestion.

Nitrates should not be administered to patients who have taken any phosphodiesterase inhibitor for erectile dysfunction within the last 24 hours (extend timeframe to 48 h for tadalafil). Their use is in symptomatic relief and preload reduction. Administer to all patients with acute myocardial infarction within the first 48 hours of presentation, unless contraindicated (ie, in right ventricular infarction).

Angiotensin-converting enzyme inhibitors

ACE inhibitors reduce mortality rates after myocardial infarction. Administer ACE inhibitors as soon as possible as long as the patient has no contraindications and remains in stable condition. An ACE inhibitor (Captopril) should be given orally within the first 24 hours of an acute coronary syndrome to patients with pulmonary congestion or LVEF less than 40% in the absence of hypotension. ACE inhibitors have the greatest benefit in patients with ventricular dysfunction. Continue ACE inhibitors indefinitely after myocardial infarction.

Angiotensin-receptor blockers

Angiotensin-receptor blockers may be used as an alternative to ACE inhibitors in patients who develop adverse effects, such as a persistent cough. An angiotensin-receptor blocker (valsartan or candesartan) should be administered to patients with ACS who are intolerant of ACE inhibitors and who have either clinical or radiologic signs of heart failure or an LVEF of less than 40%.

Beta-blockers

Beta-blockers are believed to reduce the rates of reinfarction and recurrent ischemia and should be administered to all patients with myocardial infarction unless a noteworthy contraindication exists. Both ACC/AHA 2007 guidelines for STEMI and UA/NSTEMI give oral beta-blocker usage a class I indication within the first 24 hours.

Specific contraindications to usage of this therapy include: (1) signs of heart failure, (2) evidence of a low output state, (3) increased risk for cardiogenic shock, (4) PR interval greater than 0.24 seconds (second- or third-degree heart block, and (5) active asthma or reactive airway disease. [28, 61] Metoprolol is the standard of care and is a selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. Intravenous beta-blockers have a class IIa recommendation, meaning that they may also be used in ACS if the patient is hypertensive and does not have a contraindication. [28, 61, 70]

L-carnitine

Compared with placebo, L-carnitine is associated with a 27% reduction in all-cause mortality, a 65% reduction in ventricular arrhythmias, and a 40% reduction in anginal symptoms in patients experiencing an acute MI, according to a systematic review and meta-analysis of 13 studies involving 3629 patients. The beneficial impact of L-carnitine seemed to come from its ability to limit infarct size and stabilize the cardiomyocyte membrane. [83, 84]

Lidocaine

Note that routine use of lidocaine as prophylaxis for ventricular arrhythmias in patients who have experienced a myocardial infarction has been shown to increase mortality rates; its use is class indeterminate.

A retrospective study, however, showed some benefits from administration of prophylactic lidocaine upon return of spontaneous circulation (ROSC) after out-of-hospital cardiac arrest from shock-refractory ventricular fibrillation/ventricular tachycardia (VF/VT). In the study, 1296 of 1721 patients received lidocaine at first ROSC. [85, 86]

In multivariate analyses, prophylactic lidocaine reduced the risk of rearrest from recurrent VF/VT by two-thirds and the risk of recurrent cardiac arrest from nonshockable arrhythmias by about half. Use of lidocaine was also linked to a higher likelihood of admission to the hospital and survival to discharge.

In a smaller, propensity score–matched sensitivity analysis, however, lidocaine was associated with a lower incidence of recurrent VF/VT arrest (22.8% vs 38.5%) but with no other outcome benefits. [85, 86]

Calcium channel blockers

The use of calcium channel blockers in the acute setting has come into question, with some randomized, controlled trials and retrospective studies showing increased adverse effects. However, in patients with continuing/frequently recurring ischemia and in whom beta-blockers are contraindicated, nondihydropyridine calcium channel blockers such as diltiazem and verapamil can be used only in the absence of pulmonary edema, AV block, and severe left ventricular dysfunction. [28, 70]

NSAIDs

With the exception of aspirin, both selective and nonselective cyclooxygenase (COX) inhibitors should not be used during the hospitalization of patients with ACS. An increased risk in mortality may result. NSAID use in this setting is associated with an increased risk of reinfarction, hypertension, heart failure, and myocardial rupture. Therefore, patients routinely taking NSAIDs should have these discontinued at the time of presentation. [28, 61]

Further supporting evidence comes from a large Danish study, which concluded that post-discharge NSAID use following MI, even short-term (< 7 days), increases the risk of cardiovascular events in patients with established cardiovascular disease. [87] Diclofenac was associated with the highest risk 1 week. Naproxen was the only NSAID not associated with increased risk of death/re-MI over a 14-week period.

Percutaneous Coronary Intervention

PCIs are a group of catheter-based technologies used to establish coronary reperfusion. Angiography, which provides essential knowledge of the extent of coronary disease, is performed prior to PCI. In regard to STEMI, PCI may then be performed as a primary intervention or as an intervention after thrombolysis failure. In patients presenting with unstable angina or NSTEMI, PCI is an appropriate revascularization strategy for individuals with a favorable risk factors and coronary anatomy.

The Counterpulsation and Infarct Size in Patients With Acute Anterior Myocardial Infarction (CRISP AMI) trial studied tried to determine whether routine intra-aortic balloon counterpulsation (IABC) placement prior to reperfusion in patients with anterior STEMI without shock reduces myocardial infarct size. Their findings suggest that among this group of patients, routine IABC plus primary PCI compared with PCI alone did not result in reduced infarct size. [88]

Percutaneous coronary intervention versus thrombolysis

Evidence suggests that primary PCI is more effective than thrombolysis and should be performed for confirmed STEMI, new or presumably new left bundle-branch block (LBBB), severe congestive heart failure, or pulmonary edema if it can be performed within 12 hours of symptom onset. Door-to-balloon time should be 90 minutes or less. PCI is the treatment of choice in most patients with STEMI.

In several randomized trials and registries, primary PCI (performed predominantly in experienced centers) increased patency rates of the infarct vessel at 90 minutes (85-90% for PCI vs 65% for thrombolysis).

An important advantage of performing primary PCI in myocardial infarction is the ability to achieve reperfusion of the infarct vessel with a lower risk of bleeding than that associated with thrombolytic therapy. In addition, PCI can be used to obtain instant knowledge about the extent of the underlying disease.

Patients who are treated with primary PTCA generally have shorter lengths of stay in the hospital and consume fewer medical resources than do patients treated with IV thrombolysis.

Several randomized trials have demonstrated that rapidly available primary PTCA, performed by skilled operators, for acute myocardial infarction is associated with long-term outcomes similar to those achieved with IV thrombolysis, although this comparison remains a topic of active investigation.

In systematic overviews of trials of 2635 patients who were collectively enrolled, 30-day and 6-month mortality rates were lower with primary PTCA than with thrombolysis. [89] (Door-to-balloon times correlate closely with mortality rates, making this the key measurement for any successful intervention program.) The rate of recurrent infarctions was also lower in patients treated with primary PTCA.

In addition, primary PTCA was associated with significant reductions in total stroke and hemorrhagic stroke. Therefore, primary PTCA appears to be superior to thrombolytic therapy when performed promptly in experienced centers with a well-staffed invasive angiography team.

However, the availability and accessibility of primary PCI is a very important consideration to the selection of a reperfusion strategy in patients presenting with STEMI because delays in therapy decrease myocardial salvage. If thrombolysis can be initiated 90 minutes before primary PCI is performed, then thrombolysis is preferred. [61]

Data from nonrandomized studies have suggested an advantage to the use of primary PTCA in patients with acute myocardial infarction that is complicated by cardiogenic shock. In addition, PTCA is clearly the treatment of choice for patients with contraindications to thrombolytic agents.

Whether certain subsets of patients respond better to PTCA or thrombolysis is unclear. For example, in patients with type 2 diabetes, elective PTCA is inferior to CABG, and similar or other characteristics may ultimately guide the choice among reperfusion therapies for acute myocardial infarction.

The widespread use of stenting and adjunctive IIb/IIIa therapy is improving the results of primary PCI. In one trial, coronary stenting and abciximab in patients with acute myocardial infarction led to a greater degree of myocardial salvage and a better clinical outcome than did fibrinolysis with thrombolytic therapy. [90] Improvements in short- and long-term outcomes, however, depend highly on the speed with which reperfusion is achieved.

In a study by Cantor et al, a significant decrease in ischemic complications was observed in high-risk patients with STEMI who presented at hospitals without PCI capabilities who were treated with fibrinolysis and then transferred to another hospital for PCI. [91] This study randomized 1059 patients to either standard treatment (which, if needed, included rescue PCI or delayed angiography) or immediate transfer to another hospital, where they received PCI within 6 hours following fibrinolysis. All patients received aspirin, tenecteplase, and anticoagulation (heparin or enoxaparin), and clopidogrel was recommended.

The choice of primary PCI should be individualized to each institution and to the patient's presentation and timing. PCI in patients whose arteries have been occluded for more than 24 hours appears to offer no added benefit over medical treatment.

Considerations in percutaneous coronary intervention

Elective PCI should be considered for most patients receiving thrombolytic therapy in whom ischemia develops at rest, during ambulation in the hospital, or during a prehospital discharge exercise test. Complete revascularization within 3 months of myocardial infarction appears to offer outcomes better than those of repair of the infarct-related lesion alone.

A study by Vlaar et al supports existing guidelines in that multivessel PCI in patients with STEMI is associated with higher mortality. Staged PCI (for those with significant nonculprit lesions) is associated with better outcomes. [92]

Only an experienced operator should perform primary PTCA, and PTCA should be performed only where the appropriate facilities are available. Operators should have at least 75 cases per year, while the center should perform at least 200 cases per year as per the recommendations of the ACC.

The 2009 focused updates to the ACC/AHA STEMI and PCI guidelines include recommendations for interventions and supportive measures for PCI [67] :

• Prasugrel is a reasonable alternative to clopidogrel for antiplatelet therapy during PCI, unless the patient has a history of stroke or transient ischemic attack.

• Thrombus aspiration is reasonable for primary PCI.

• Fractional flow reserve can be useful to determine whether a specific lesion should be stented.

An updated meta-analysis of 25 trials including 5534 patients found that thrombus aspiration before angioplasty reduced major adverse cardiac events (MACE) but did not affect infarction size. [93, 94] Aspiration thrombectomy was linked with significantly (P< 0.0001) higher rates of TIMI (Thrombolysis In Myocardial Infarction) 3 blush post procedure (63.6% vs 48.5%) and complete ST-segment resolution (55.8% vs 44.3%). [94] During follow-up (average, 5.9 months), all-cause mortality (the primary endpoint) was significantly lower with aspiration thrombectomy than with PCI alone (2.7% vs 3.9%; P = 0.049).

Drawbacks, contraindications, and risk factors for percutaneous coronary intervention

Diagnostic coronary angiography post thrombolysis may be performed; however, further studies are needed to clarify the role and benefit of routine PCI to the infarct-related artery in asymptomatic patients who demonstrate successful thrombolysis. [61] The Occluded Artery Trial (OAT) determined that PCI to a persistently occluded infarct-related artery greater than 24 hours after onset of STEMI is not currently recommended per the latest ACC/AHA 2007 guideline update. [28, 95]

Facilitated PCI with thrombolysis also is not recommended in the guidelines because this approach may be harmful. Facilitated PCI refers to giving thrombolysis immediately prior to planned, urgent PCI. [61]

A drawback of PCI is the need for 24-hour availability of an angioplasty suite with the required staff and the availability of backup cardiothoracic capabilities. Primary PCI for STEMI should be performed at hospitals with readily available cardiothoracic surgery. (“Readily available” may be defined as the ability to transport patients quickly to a hospital with cardiothoracic capabilities.)

No absolute contraindications are described for coronary arteriography. Relative contraindications include the following:

• Unexplained fever

• Untreated infection

• Severe anemia with hemoglobin level less than 8 g/dL

• Severe electrolyte imbalance

• Severe active bleeding

• Uncontrolled systemic hypertension

• Digitalis toxicity

• Previous allergy to contrast material but no pretreatment with corticosteroids

• Ongoing stroke

• Acute renal failure

• Decompensated CHF

• Severe coagulopathy

• Diabetic patients with Cr greater than 2

• Patients on metformin (Glucophage) or other oral hypoglycemic agents

• Active endocarditis

Risk factors for clinically significant complications after catheterization include advanced age, hemodynamic instability, multisystemic disease, large infarctions, bleeding disorders, and extensive atherosclerosis in the aorta or access arteries.

Disadvantages of primary PTCA include the fact that the procedure is highly dependent on the operator's skill and that immediate access to highly skilled operators is necessary. [96]

Percutaneous coronary intervention in high-risk patients

Primary PCI appears to have a particular advantage over thrombolysis for the management of high-risk myocardial infarction patients, such as those with diabetes and the elderly. In an analysis of patients who were receiving Medicare in the Cooperative Cardiovascular Project database, primary PCI improved 30-day and 1-year survival. The benefits of primary PCI in the elderly persisted after stratification by the number of myocardial infarction patients cared for at individual hospitals and the presence of on-site angiography. When the transit time to such a facility is 90 minutes or more, facilitated half-dose thrombolysis followed by PCI may be effective. The risk of this approach may be lower than that of full-dose thrombolysis, and patency rates are greater than that of late PCI without lysis.

Availability of percutaneous coronary intervention

Although reports from individual community hospitals replicating the results in randomized trials may be found in the literature, less than 20% of hospitals in the United States and less than 10% of hospitals in Europe can perform primary PCI. An even smaller percentage of hospitals are performing PCI on an emergency basis 24 hours a day, 7 days a week. Whether low-volume PCI centers with relatively inexperienced investigators can replicate the encouraging results reported to date remains to be determined. In addition, whether on-site cardiac surgical backup is a necessary component of a primary PCI strategy for myocardial infarction is unclear.

Coronary Artery Bypass Graft Surgery

Emergent or urgent CABG surgery is indicated in patients in whom angioplasty fails and in patients who develop mechanical complications, such as a ventricular septal defect, LV, or papillary muscle rupture.

No-Reflow Phenomenon

If, after medical therapy with fibrinolytic drugs, percutaneous intervention with angioplasty, surgery, or spontaneous resolution, coronary blood flow does not resume relatively promptly, good myocardial perfusion may not be achieved despite restoration of luminal patency. [97] This situation is known as the no-reflow phenomenon; it occurs because of swelling of endothelial cells, formation of platelet and leukocyte plugs, or complement-mediated microvascular inflammation.

New Treatment Strategies

Interventionalists have begun to embrace new treatment strategies, such as the use of stenting and IV platelet GPIIb/IIIa inhibitors, to improve results of PTCA in acute myocardial infarction. Stents that elute drugs such as sirolimus and paclitaxel may inhibit endothelial proliferation, prevent early closure, and improve results. This stenting appears to be more effective than brachytherapy (irradiation).

Patients with evolving chest pain and ST-segment elevations that persist for 90 minutes after the administration of a thrombolytic agent may be candidates for emergency catheterization, and, if the infarct-related vessel is occluded, for “rescue” PCI. [98]

Local injection of progenitor cells, growth factors, or genes may stimulate vascular development. Investigators in a double-blinded study, the Reinfusion of Enriched Progenitor Cells And Infarct Remodeling in Acute Myocardial Infarction (REPAIR-AMI) study, examined 204 patients with acute STEMI; they reported demonstrated greater improvement in LVEF among patients receiving intracoronary progenitor cell infusion than among patients given placebo. [99]

Some clinical trial results suggest that intracoronary delivery of autologous bone marrow mononuclear cells (BMCs) have improved LV function when administered within the first week following myocardial infarction. The LateTIME Randomized Trial tested whether intracoronary delivery of autologous BMCs improved global and regional LV function compared with placebo when delivered 2-3 weeks following first myocardial infarction. The results suggest that those patients with myocardial infarction and LV dysfunction following reperfusion with PCI show little improvement from this therapy. [100]

ICDs may be unnecessary in select post-MI patients with severe LV dysfunction and negative EPS

Zaman et al reported that patients with severe LV dysfunction and a negative electrophysiology study (EPS) showing no inducible ventricular tachycardia (VT) have low long-term rates of arrhythmia or death without receiving an implantable cardioverter defibrillator (ICD). [101, 102] The rates were shown to be similar to those observed in patients with preserved LV ejection fraction (EF). [102] In their study, LVEF assessment was performed on consecutive patients treated with coronary angioplasty for ST-segment-elevation MI (STEMI), including 128 patients with an LVEF of 30% or less or with an LVEF of 35% or less with New York Heart Association (NYHA) class 2 or 3 heart failure, as well as 1286 control patients with an LVEF greater than 40% (not eligible for EPS). [101, 102]

ICDs were implanted in less than 0.1% of control patients, 4% of patients with a negative EPS, and 90% of those with a positive EPS. [101, 102] At 3-year follow-up, 91.8% of controls and 93.4% of EPS-negative patients were alive and without arrhythmia, whereas 62.7% of patients with LV dysfunction and a positive EPS were alive and without arrhythmia. [101, 102]

Special Concerns for Elderly Patients

Elderly patients with acute myocardial infarction are at increased risk of developing complications. Treat these patients aggressively. Elderly patients have an increased risk of bleeding with thrombolytic therapy, but they also have the most to gain from this treatment.

Very elderly patients should undergo primary angioplasty if available, but they should receive thrombolytic agents if excessive delay is anticipated before angioplasty can be performed.

Diet

Initially, keep the patient on nothing by mouth (NPO) until his or her condition has been stabilized and treated. Following the patient’s initial therapy and admission, a dietitian should instruct the patient regarding appropriate diet, as recommended by the AHA. A low-salt, low-fat, and low-cholesterol diet is generally recommended.

Activity

Confine patients to bed rest to minimize oxygen consumption until reperfusion and initial therapy are complete. This usually lasts about 24-48 hours; after that, the patient's activity may be accelerated slowly as tolerated and as the clinical situation allows. Initiate cardiac rehabilitation prior to discharge.

Complications

Complications of myocardial infarction include arrhythmic complications, mechanical complications, left ventricular aneurysm, ventricular septal rupture, associated right ventricular infarction, pseudoaneurysm, and other miscellaneous complications, all of which are discussed in general below. For more information, see Complications of Myocardial Infarction.

Arrhythmic complications

Cardiac arrhythmias are not uncommon during and immediately after an acute myocardial infarction. Of all patients who have an acute myocardial infarction, about 90% develop some form of cardiac arrhythmia. In 25% of patients, such rhythm abnormalities manifest within the first 24 hours. In this group of patients, the risk of serious arrhythmias, such as VF, is greatest in the first hour and declines thereafter. The incidence increases with an STEMI and decreases with NSTEMI.

The clinician must be aware of these arrhythmias, in addition to reperfusion strategies, and he or she must treat those that require intervention to avoid exacerbation of ischemia and subsequent hemodynamic compromise. Most peri-infarct arrhythmias are benign and self-limited. However, those that result in hypotension, increase myocardial oxygen requirements, and/or predispose the patient to develop additional malignant ventricular arrhythmias should be aggressively monitored and treated.

Mechanical complications

The 3 major mechanical complications of myocardial infarction, each of which can cause cardiogenic shock, are as follows:

• Ventricular free wall rupture

Left ventricular aneurysm

Left ventricular aneurysm is defined as a localized area of myocardium with abnormal outward bulging and deformation during systole and diastole. The rate of left ventricular aneurysms after acute myocardial infarction is approximately 3-15%. Risk factors for these aneurysms after acute myocardial infarction include the following:

• Female sex

• Total occlusion of the LAD artery

• Single-vessel disease

• Absence of previous angina

On clinical evaluation, ventricular aneurysms may be recognized late, with symptoms and signs of HF, recurrent ventricular arrhythmia, or recurrent embolization.

Ventricular septal rupture

Ventricular septal rupture is a rare, but lethal, complication of myocardial infarction. The event occurs 2-8 days after an infarction and often precipitates cardiogenic shock. The differential diagnosis of postinfarction cardiogenic shock should exclude free ventricular wall rupture and rupture of the papillary muscles. To avoid the high morbidity and mortality associated with this disorder, patients should undergo emergent surgery. [103, 104] Concomitant coronary artery bypass may be required. Developments in myocardial protection and improved prosthetic materials have contributed greatly to successful management of ventricular septal rupture. [105] Long-term survival can be achieved in patients who undergo prompt surgery.

Ventricular rupture occurs in the interventricular septum or the left ventricular free wall. Rupture in either location is a catastrophic event, with the mortality rate being greater than 90%. Prompt recognition, stabilization, and surgical repair are crucial to any hope of patient survival. Ventricular rupture is more common in women, patients with hypertension, and those receiving nonsteroidal anti-inflammatory drugs (NSAIDs) or steroids. An echocardiogram can usually define the abnormality, and a right heart catheterization can show an oxygen saturation step-up in the case of a septal rupture.

Associated right ventricular infarction

Approximately one third of patients with inferior myocardial infarction develop RV infarction. RV infarction presents a special challenge because the adjunctive therapy, other than reperfusion, is somewhat different.

A right-sided ECG with greater than 1 mm ST elevation in V3 R or V4 R leads describes an RV infarct. An echocardiogram may be helpful in confirming the diagnosis. On physical examination, signs of right heart failure, such as elevated jugular venous pulsation, right-sided S3, Kussmaul sign, or hypotension, may be present, and the patient may have clear lung fields.

The patient becomes volume dependent to maintain adequate LV and RV filling. Occasionally, dobutamine may be needed, or even an intra-aortic balloon pump for hemodynamic support.

Avoid nitrates or any medications that lower preload in this setting. A pulmonary artery catheter can be helpful in guiding therapy.

For more information, see Right Ventricular Infarction.

Pseudoaneurysm

Complications of myocardial infarction, such as pseudoaneurysm, are confirmed by means of echocardiography, MRI, or contrast-enhanced CT scanning. Imaging of a pseudoaneurysm typically shows a relatively narrow neck and a complete absence of muscle in the wall of the pseudoaneurysm, unlike a true aneurysm, which has a rim of myocardial wall that may be identified on angiograms by the presence of mural vessels.

Miscellaneous complications

Left ventricular mural thrombus is a well-known complication of acute myocardial infarction and frequently develops after anterior infarcts of the LV wall. The incidence of left ventricular mural thrombus as a complication of acute myocardial infarction ranges from 20-40% and may reach 60% in patients with large, anterior-wall acute myocardial infarctions who are not treated with anticoagulant therapy. Left ventricular mural thrombus is associated with a high risk of systemic embolization. Anticoagulant therapy may substantially decrease the rate of embolic events by 33% compared with no anticoagulation.

The incidence of early pericarditis after myocardial infarction is approximately 10%, and this complication usually develops within 24-96 hours. Pericarditis is caused by inflammation of pericardial tissue overlying infarcted myocardium. The clinical presentation may include severe chest pain, usually pleuritic, and pericardial friction rub.

Before the era of reperfusion, the incidence of post-myocardial infarction syndrome (Dressler syndrome) ranged from 1-5% after acute myocardial infarction, but this rate has dramatically declined with the advent of thrombolysis and coronary angioplasty.

For more information, see Complications of Myocardial Infarction.

Transfer

A study showed that the transfer of patients to an invasive-treatment center for primary PCI is superior to on-site fibrinolysis provided that the transfer can be accomplished within 2 hours. Transfer should be considered for those patients who are likely to benefit from PCI or cardiac surgery but who are in an institution where access to such interventions is not immediate. The benefits of transferring such a patient must outweigh the risks. Patients for whom transfer might be considered include the following:

• Patients with new or worsening hemodynamically significant mitral regurgitant murmurs

• Patients with known or suspected critical aortic stenosis and either ongoing ischemia or hemodynamic instability

• Patients who have received thrombolysis and fail to reperfuse

• Patients with significant LV dysfunction or cardiogenic shock

In an aforementioned study by Cantor et al, a significant decrease in ischemic complications was observed in high-risk patients with STEMI who were treated with fibrinolysis and transferred for PCI within 6 hours following fibrinolysis. [91] This study randomized 1059 patients to either standard treatment (ie, if needed, included rescue PCI, or delayed angiography) or immediate transfer to another hospital and PCI within 6 hours following fibrinolysis. All patients received aspirin, tenecteplase, and anticoagulation (heparin or enoxaparin), and clopidogrel was recommended.

The 2009 focused updates to the ACC/AHA STEMI and PCI guidelines recommend that high-risk STEMI patients who receive fibrinolytic primary reperfusion therapy be transferred to a PCI-capable facility as soon as possible. The clinician should consider starting anticoagulant plus antiplatelet treatment before and during the transfer. The same transfer and treatment may be considered for similar patients not at high risk. [67]

Deterrence and Prevention

Cigarette smoking is a major risk factor for coronary artery disease. The risk of recurrent coronary events decreases 50% at 1 year after smoking cessation. Provide all patients who smoke with guidance, education, and the support needed to avoid smoking. Bupropion has been shown to increase the chances of patients' success in achieving smoking cessation.

Varenicline (Chantix) has also been shown to aid in smoking cessation, however, a meta-analysis of double-blind, randomized controlled trials found a 72% increased risk of serious adverse cardiovascular events in patients receiving varenicline (1.06%) compared with those receiving a placebo (0.82%). [106] Serious adverse cardiovascular events were defined as myocardial infarction, unstable angina, coronary revascularization, coronary artery disease, arrhythmias, transient ischemic attacks, stroke, sudden death or cardiovascular-related death, or congestive heart failure. [106]

A meta-analysis reported by the FDA in 2012 also showed an increased risk of serious adverse cardiovascular events in patients receiving varenicline compared to those receiving placebo. Although the events were uncommon in both groups and the risk was not statistically significant, data analysis points to the drug as the likely cause. [107]

Extreme caution should be used when considering varenicline for patients with known cardiovascular problems.

Mild alcohol consumption has been associated with a decreased risk of stroke and myocardial infarction. Cautiously consider recommending and discussing alcohol use on a case-by-case basis.

Antioxidant therapy, including vitamin E, has not shown clear benefit in the prevention of coronary events.

Do not use long-term anticoagulant (ie, warfarin) therapy routinely in post–myocardial infarction patients, but employ it as an alternative in patients who cannot take antiplatelet agents. Patients with known left ventricular thrombus, atrial fibrillation, or severe wall motion abnormalities have shown benefit from long-term anticoagulation, maintaining the international normalized ratio (INR) between 2 and 3.

Low-dose aspirin has shown substantial benefit for primary prevention of myocardial infarction and stroke, but its use must be weighed against the risk for hemorrhagic stroke and gastrointestinal bleeding. A study in the United Kingdom suggests that the discontinuation of low-dose aspirin therapy in individuals with a history of cardiovascular events are at an increased risk of nonfatal myocardial infarction compared with those who continue treatment. [108]

In the aforementioned Antithrombotic Trialists' (ATT) Collaboration study, aspirin was associated with significant reduction (12% proportional reduction) for serious vascular events (0.51% aspirin vs 0.57% control annually), but the net effect on stroke was not significant. [78] The use of aspirin for primary prevention must be advised in context with the patient’s personal risks and history.

In 2010, the American Heart Association-American Stroke Assocation issued its guidelines for the primary prevention of stroke. They advised that screening patients 65 years of age and older for atrial fibrillation (AF) in the primary care settings using pulse taking followed by an ECG may be useful. They also advised that adjusted-dose warfarin should be used for all patients with nonvalvular AF (target INR 2-3). Aspirin is recommended for low and moderate-risk patients with AF; for high-risk patients unsuitable for anticoagulation, a combination of clopidogrel and aspirin may offer better protection against stroke than aspirin alone. [109]

In 2014, the FDA released study results of more than 134,000 Medicare patients in which there was no increased risk of MI with dabigatrin (Pradaxa) compared with warfarin. [110, 111] Dabigatrin was also associated with a lower risk of clot-related strokes, bleeding in the brain, and death than warfarin. However, the risk of major gastrointestinal bleeding was higher in the dabigatrin-treated group than the group receiving warfaran. As a result of the findings, the FDA still considers dabigatrin to have a favorable benefit to risk profile. [110, 111]

Do not start post–myocardial infarction patients on postmenopausal hormone therapy. However, patients who have already been undergoing such treatment for more than 1 year may be continued on it without increased risk.

In a case-control study of 559 Australian patients, 275 with acute MI (AMI) and 284 without, vaccination against the influenza virus reduced the risk of ischemic events, even though the influenza virus itself was not a significant predictor of AMI. [112, 113]

In all, 12.4% of the vaccinated subjects and 6.7% of the control subjects had influenza (odds ratio, 1.97; 95% confidence interval [CI], 1.09–3.54). [113] After adjustment for confounding variables (eg, age, male sex, high cholesterol levels, current smoker status, and influenza vaccination in the study year), influenza exposure was not associated with a risk of AMI despite the association observed in univariate analysis. In the multivariate analysis, flu vaccination was associated with a 45% reduction in AMI risk.

Consultations

The decision to administer a thrombolytic agent may be made by the emergency physician, with or without the input of a cardiologist, depending on institutional protocol. In a center with the full range of treatment options, an expeditious phone consultation with a cardiologist would seem to be a wise choice to ascertain the best possible option for the patient.

Obtain cardiologic consultation immediately if primary PCI is considered. Otherwise, such consultation may be obtained as needed and upon admission. Consultation may be obtained sooner if the patient presents with significant heart failure, mechanical complications, arrhythmias, or other complicating factors.

A cardiologist should be consulted for the following:

• Patients who may benefit from PCI, including "rescue PCI," with transfer if required, for patients in whom thrombolysis for STEMI fails to achieve reperfusion

• Patients in cardiogenic shock

• Patients with hemodynamically significant new or worsening murmur

• Patients who are not candidates for thrombolytic intervention because of a contraindication

• Intractable angina despite medications

• Severe pulmonary congestion

• Late presentation (>3 h but no more than 12 h)

• Where the diagnosis is in doubt

Note that PCI door-to-balloon time should be less than 90 minutes.

Immediate and Short-Term Monitoring

Admit patients with myocardial infarction to a coronary care unit. Monitor patients carefully for arrhythmia, recurrent ischemia, and other possible complications. The patient may be transferred to a telemetry unit 24-48 hours after admission if no complications occur. Hospitalize the patient for approximately 4-5 days after myocardial infarction. Patients who undergo primary PCI or have an immediate cardiac catheterization may be discharged sooner if their hospital course is without incident.

Perform a coronary angiography on high-risk patients prior to discharge to evaluate their need for revascularization. In the case of patients who have not had a cardiac catheterization and have no complications, perform a submaximal stress test prior to discharge to assess their subsequent risk. To stratify mortality risk after PCI for acute myocardial infarction, Negassa et al developed a prognostic classification model. Patients can be readily stratified into risk categories using this tree-structured model. [114]

Wang et al analyzed Medicare and Medicaid data, examining hospitals for adherence to the AHA Get with the Guidelines recommendations after myocardial infarction and for heart failure. Those who adhered to guidelines for both had reduced in-hospital mortality (hazard ratio 0.79) compared with those who adhered to one guideline or neither one. [115]

Long-Term Monitoring

Arrange for follow-up within 2 weeks of discharge. Arrange for cardiac rehabilitation.

Current guidelines strongly recommend the use of aldosterone antagonists after MI for patients with left ventricular systolic dysfunction concomitant with either clinical heart failure or diabetes mellitus. However, an analysis of data on 202,213 US patients discharged following an acute myocardial infarction found that only 14.5% of eligible patients received aldosterone antagonists at the time of discharge. Among eligible patients who were discharged on otherwise optimal medical therapy (68.9%), 16.1% were prescribed aldosterone antagonists. [116]

The long-term use of aspirin in patients who have had a myocardial infarction results in significant reduction in subsequent mortality rate. The prescription of 75-162 mg/d of aspirin indefinitely is a class I recommendation for patients with NSTEMI who are treated medically without stenting, according to the 2011 update of the ACC Foundation (ACCF)/AHA guidelines on unstable angina/NSTEMI. [117] Beta-blocker therapy has confirmed therapeutic benefit in survivors of acute myocardial infarction. This therapy is most beneficial in patients with the highest risk.

The use of ACE inhibitors in patients with known coronary artery disease has been shown to reduce mortality rate.

Many trials have shown a clear benefit from lipid-lowering therapy in the secondary and primary prevention of coronary artery disease. The National Cholesterol Education Panel has set guidelines for target cholesterol levels. In general, patients who have experienced myocardial infarction should achieve a low-density a lipoprotein (LDL) level of less than 100 mg/dL, a high-density lipoprotein (HDL) level of greater than 40 mg/dL, and a triglyceride level of less than 200 mg/dL. High-risk patients should be treated to a target LDL level of less than 70 mg/dL.

Schwartz et al showed in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial that initiating atorvastatin during hospitalization for an acute coronary syndrome, irrespective of lipid levels, reduces the frequency of recurrent ischemic events. This treatment significantly reduced the frequency of the combined end point of death, recurrent death, myocardial infarction, or worsening unstable angina requiring hospitalization. [118]

Clopidogrel should be prescribed for a year following discharge if the patient has no contraindications and cost is not prohibitive. To reduce the risk of bleeding, the aspirin dose can be reduced to 81 mg.

Data from a study of 24,317 consecutive survivors of an acute MI with atrial fibrillation and known serum creatinine show that regardless of the severity of renal dysfunction, the 1-year risk of death, MI, or stroke was significantly lower among patients prescribed warfarin at discharge compared with those who were not. Of the total patients, 5,292 (21.8%) were prescribed warfarin at discharge, and 51.7% had chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73m2. [119, 120]

At 1 year, after adjustment for age, sex, center, eGFR, preexisting cardiovascular (CV) comorbidities and cancer, syndrome at presentation, revascularization at index hospitalization, and discharge CV medication, the hazard ratio for death, MI, or ischemic stroke among patients who received warfarin was 0.73 for all patients, 0.73 for those with eGFR >60, 0.73 for those with eGFR >30 to 60, 0.84 for those with eGFR >15 to 30, and 0.57 for those with eGFR < 15. The adjusted risk of bleeding was not significantly higher in patients who received warfarin in any eGFR group. [119, 120]

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Author

A Maziar Zafari, MD, PhD, FACC, FAHA Professor of Medicine, Emory University School of Medicine; Chief of Cardiology, Atlanta Veterans Affairs Health Care System; Adjunct Professor of Medicine, Morehouse School of Medicine

A Maziar Zafari, MD, PhD, FACC, FAHA is a member of the following medical societies: American College of Cardiology, American Heart Association

Disclosure: Nothing to disclose.

Coauthor(s)

Shilpa V Reddy, MD Fellow in Cardiovascular Disease, Division of Cardiology, Emory University School of Medicine

Shilpa V Reddy, MD is a member of the following medical societies: American College of Cardiology

Disclosure: Nothing to disclose.

Ahmad M Jeroudi, MD Fellow in Cardiovascular Disease, Division of Cardiology, Emory University School of Medicine

Disclosure: Nothing to disclose.

Samer M Garas, MD, FACC, FSCAI Interventional Cardiologist, President, St Vincent's Health System Cardiovascular Council

Samer M Garas, MD, FACC, FSCAI is a member of the following medical societies: American College of Cardiology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Eric H Yang, MD Associate Professor of Medicine, Director of Cardiac Catherization Laboratory and Interventional Cardiology, Mayo Clinic ArizonA

Eric H Yang, MD is a member of the following medical societies: Alpha Omega Alpha

Disclosure: Nothing to disclose.

Acknowledgements

David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair, Department of Emergency Medicine, Massachusetts General Hospital

David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Drew Evan Fenton, MD, FAAEM Private Practice

Disclosure: Nothing to disclose.

Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division of Emergency Medicine, Harvard Medical School

Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine

Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management position; ProceduresConsult.com Royalty Other

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Eric Vanderbush, MD, FACC Chief, Department of Internal Medicine, Division of Cardiology, Harlem Hospital Center; Clinical Assistant Professor of Cardiology, Columbia University College of Physicians and Surgeons

Eric Vanderbush, MD, FACC is a member of the following medical societies: American College of Cardiology and American Heart Association

Disclosure: Nothing to disclose.

Which is the appropriate analgesic to relieve chest pain in a client with myocardial infarction?

Which drug should be administered as the initial management for a patient with chest pain consistent with a myocardial infarction?

Which analgesic is used in severe pain of myocardial infarction?

What medications are given after a myocardial infarction?