Short Description

This algorithm provides an efficient way for the resuscitation team to determine if a patient with ACS is a candidate for the administration of fibrinolytic therapy.

Algorithm at a Glance

• The fibrinolytic checklist is a convenient way for the team leader to quickly recall the indications and contraindications for fibrinolytic therapy.
• For ACS with symptoms that began > 12 hours before presentation to the ED, the provider considers a PCI transfer.
• For ACS with symptoms that began < 12 hours before presentation to the ED, the provider considers the administration of fibrinolytics after assessing for contraindications and risk.

Goals for the Fibrinolytic Checklist

The provider will:

• Understand the importance of timing in the checklist.
• Understand the use of ECG findings to determine the patient’s appropriateness for fibrinolytic therapy.
• Understand relative and absolute contraindications for the use of fibrinolytics.

Fibrinolytic Therapy Checklist

Box 1: Timing of Symptoms

If the patient’s ACS symptom duration is > 12 hours, they are outside the window to administer fibrinolytics, and the provider considers a transfer for PCI. If the symptoms began < 12 hours before presentation, the provider proceeds to Box 2.

Box 2: ECG Findings

The team leader evaluates the patient’s ECG and makes a diagnosis.

If the 12-lead ECG shows an ST elevation myocardial infarction (STEMI) or new left bundle branch block (LBBB), the provider proceeds to Box 3. If STEMI or LBBB is not apparent, the checklist is discontinued.

Box 3: Contraindications to Fibrinolytic Therapy

The provider answers each question to ascertain whether fibrinolytic therapy may be contraindicated. If the answer to any of the questions is Yes, the provider must use their best clinical judgment to determine if the treatment should proceed. 

If the benefits of fibrinolytics outweigh the risks, the provider proceeds to Box 4.

Box 4: Is the Patient at High Risk?

The team determines the answers to these questions:

• Is the heart rate > 100 beats/min and SBP < 100 mm Hg?
• Does the patient have symptoms of pulmonary edema?
• Does the patient have signs or symptoms of shock?
• Are there other contraindications to fibrinolytic therapy?

If the answer to any of these questions is Yes, the provider proceeds to Box 5. Otherwise, the team proceeds with the administration of fibrinolytics.

Box 5: Considering Transfer to a Cardiac Catheterization Lab for PCI Therapy

If the patient is NOT a candidate for fibrinolytic therapy, the provider considers transferring the patient to the in-house cardiac catheterization lab or to a hospital with those facilities. The team must not delay PCI therapy if it is available.

Interventions for Inpatients

Surprisingly, patients in the hospital with ACS may have a longer interval before symptoms are recognized, even if they receive appropriate interventions. This may be because inpatients are a more mixed population or possibly due to inefficiencies in the coordination of hospital care for such emergencies.

Similar strategies for outside hospital care can work in the hospital setting, including the integration of care and optimization of the survival chain. Additionally, auditing ACS patient outcomes and the time to care is a useful strategy for determining policies that will minimize time delays for future inpatients with STEMI.  

Empiric Treatment for ACS

For all patients suspected of having ACS, these four therapies should be given immediately, ensuring there are no allergies or contraindications first:

• nasal oxygen for O₂ saturation under 90% or dyspnea
• chewable aspirin 162–325 mg (if no allergy/contraindication)
• sublingual nitroglycerin (or spray) 
• IV morphine 2–4 mg as needed for chest pain refractory to nitroglycerin

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Treating Pain

Managing pain is not only appreciated by patients, but ischemic pain increases catecholamine release, thereby increasing heart rate, contractility, and systemic blood pressure and leading to increased cardiac oxygen demand that worsens ischemia and increases the likelihood of hemodynamic complications.

The benefits of good pain management include:

• decreased cardiac oxygen demand (nitrates, beta-blocker, morphine)
• minimizing catecholamine release (beta-blocker)
• decreasing anxiety (morphine)

Oxygen

In the first 24 hours, as many as 70% of ACS patients will have hypoxemia secondary to mismatched ventilation and perfusion or minor pulmonary edema due to dysfunction of the left ventricle. Consequently, oxygen administration can help in ACS states, and research indicates it reduces ST elevation in anterior MIs.

ACS is already characterized by suboptimal oxygenation, so providing oxygen is likely helpful for limiting the spread of the infarct and the extent of the resultant cardiac compromise. These findings, however, are not readily evaluated in clinical studies, as some research indicates no benefit of oxygen in terms of survival and long-term clinical outcomes.

All patients with dyspnea, shock, heart failure signs, or oxygen saturation below 90% should receive oxygen. The goal should be to maintain oxygen saturations above 90%. There is no evidence that ACS patients with normal oxygen saturations benefit from providing supplemental oxygen.

Education should focus on the importance of prompt identification and EMS activation, rapid CPR, and defibrillation.

Oxygen is an ACS empiric treatment.

Aspirin

Studies show that aspirin can help decrease mortality while being safe for patients without contraindications. The dose is 162–325 mg of uncoated aspirin that is chewed, not swallowed, as this improves absorption. Patients who cannot chew (e.g., difficulty swallowing, emesis, or upper GI problems) should be given a 300 mg rectal aspirin suppository. The mechanism of action is rapid inhibition of cyclooxygenase (COX-1) and thromboxane A2 production, which limit platelet aggregation and subsequent thrombosis. Aspirin is also important for patients following cardiac stenting, as it decreases the risk of thrombus formation post-stent.

Aspirin benefit in ACS was demonstrated in the classic fibrinolysis trials. These showed that aspirin reduced mortality from MI and improved outcomes when added to thrombolytics like streptokinase. Since fibrinolytics expose intravascular thrombin, aspirin is needed to prevent activation of platelet aggregation, which can make thrombosis worse following fibrinolytic administration. When aspirin was given with fibrinolytics, there was a reduction in thrombotic events (to 10% from 14%) and a reduction in AMI of 30% in high-risk patients and vascular causes of death of 17%.

Aspirin Tablets

The contraindications to aspirin for ACS patients include true allergies or recent GI bleeding. True allergies include anaphylaxis or hives. The alternative, in this case, is clopidogrel. Also, individuals with asthma or severe allergies may have a true aspirin allergy. Most other patients with suspected ACS should get aspirin due to the life-threatening nature of the disease. Some patients may state they have an allergy but really have an intolerance such as indigestion or upset stomach with aspirin.

Contraindications to aspirin for ACS include: 

• significant nausea/emesis or peptic ulcer disease
• true allergy (hives/anaphylaxis) 
• GI bleeding
• bleeding diathesis 
• severe liver disease

Note that other nonsteroidal anti-inflammatory drugs (NSAIDs) should not be substituted for aspirin as these are associated with worse outcomes in STEMI, including death, heart failure, and reinfarction.

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Related Video: Aspirin – ACLS Drugs

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Nitroglycerin

Nitroglycerin is effective at reducing chest pain and improving hemodynamic status in ACS. As a vasodilator, it decreases the preload of the ventricles. Additionally, it causes dilation of the coronary vessels, improving blood flow to the obstructed areas.

Sublingual or spray administration is recommended. There is no evidence of long-term benefits and no evidence for using IV, topical, or oral doses.

Important points:

• Nitroglycerin is the first-line treatment (before morphine) for ACS-related chest pain.
• The sublingual dose is 0.3–0.4 mg or spray 0.4 mg on the tongue. Repeat every 3–5 minutes up to two times if symptoms persist, and monitor blood pressure and other vital signs. 
• Continue nitroglycerin for repeat ischemic episodes within 24–48 hours. 
• Nitroglycerin is contraindicated in patients who have recently been treated with phosphodiesterase inhibitors in the past 24–48 hours (24 hours for sildenafil and vardenafil and 48 hours for tadalafil) as this can cause severe and refractory hypotension. 
• Nitroglycerin is contraindicated in hypotensive patients (SBP < 90 mm Hg) severe bradycardia (HR < 50 bpm) or tachycardia (without heart failure).
• Nitroglycerin is contraindicated in patients with MI of the inferior wall or right ventricle involvement. If there is an abnormality of the right ventricle, nitroglycerin may limit filling of the right heart, leading to poor cardiac output and hypotension. 
• Additionally, nitroglycerin should be used with caution in patients with SBP < 100 mm Hg, sinus bradycardia of 60 bpm or lower, or those with significant parasympathetic or vagal tone as they may be unable to recover from the resulting vasodilation. 
• The alternative is a topical nitrate to help with chest pain in stable patients whose symptoms are not refractory. Note that wiping the medication off may not completely reverse the action. Extended-release or long-lasting oral medications should not be used as their effects will be difficult to reverse.

Sublingual Nitroglycerin Tablets

IV Nitroglycerin for STEMI

Nitroglycerin given IV is not more effective than sublingual or spray versions and is not routinely indicated for STEMI. Additionally, it can limit the use of other medications with benefits, including beta-blockers and ACE inhibitors. IV dosing can be used in the following situations:

• persistent pain following sublingual and spray dosing
• ACS complicated by hypertension
• management of comorbid heart failure

When providing IV nitroglycerin, clinicians should ensure frequent monitoring of the patient and patient vitals. Significant hypotension associated with nitroglycerin can lead to decreased perfusion of the heart. 

• Ensure no contraindications to nitroglycerin.
• Monitor patient vitals.
• Dosing: 12.5–25 mcg IV bolus (only when no prior sublingual or spray doses given)
• Infusion rate is 10 mcg/min with the dosing adjusted as needed. The maximum rate is 200 mcg/min.
• Doses can be given only if systolic BP is > 100 mm Hg in normotensive patients or there has been no more than a 25% reduction compared to baseline in hypertensive patients.

Intravenous Nitroglycerin With Catheter and Tubing

Morphine 

Morphine is used in chest pain from STEMI that does not respond to nitroglycerin. (Class I, Evidence level C). Morphine also decreases cardiac oxygen demand by minimizing the increased adrenergic state associated with ACS.

Specifically, morphine: 

– is an analgesic that reduces the hyperadrenergic state and cardiac oxygen requirements 

– dilates veins, thereby decreasing left ventricular preload and cardiac oxygen requirements

– lowers vascular resistance and decreases afterload 

–  redistributes the blood volume in pulmonary edema

Dosing Morphine

• For STEMI, it is administered IV at 2–4 mg. Repeat doses of 2–8 mg can be given every 5–15 minutes.
• For NSTEMI, the dose is 1–5 mg IV given if the chest pain is refractory to nitrates.
• Morphine should not be given to hypotensive or hypovolemic patients because they are at risk for significant hypotension. 
• If morphine-associated hypotension occurs and there is no pulmonary edema, the legs should be elevated and the patient given a 200–500 mg IV bolus of saline and monitored closely.
• It is rare to have depressed respirations associated with morphine use in ACS, as patients usually have a hyperadrenergic state. If respirations are slowed, 0.04–0.4 mg naloxone may be given. A 0.04 mg dose can be repeated every 2–3 minutes as needed.

Intravenous Morphine

Administering Fibrinolysis Outside the Hospital

Early access to fibrinolysis improves the long-term outcomes after ACS. So there can be a benefit to administering fibrinolysis before admission to the hospital. Research indicates that providing this medication to patients in their homes saved up to 130 minutes and improved long-term survival rates over 1–5 years by 50%. Multiple randomized studies show the benefits of fibrinolysis administered pre-hospital, with a 17% improvement in all outcomes. Generally, saving between 60 and 90 minutes is associated with the best outcomes. However, it is important to note that rapid diagnosis and transport to the appropriate hospitals within 30 minutes should have similar outcomes and would minimize the need to set up strict protocols and training for the out-of-hospital administration of fibrinolysis.

The benefits must be weighed with risk. Out-of-hospital fibrinolysis improves the up to 2.5- to 3-hour delay in management seen frequently with in-hospital administration of fibrinolytics. However, some studies show that while the delay is decreased, the risk for intracranial hemorrhage, particularly in older individuals > 75 years, increases.

Whenever fibrinolysis is chosen as the treatment strategy, the goal is to administer the medication within 30 minutes of presentation. Studies indicate that if the delay from symptom onset to fibrinolysis is under 70 minutes, there is a 50% decrease in the size of infarct and a 75% decrease in death.

It is possible, therefore, that if the transport to the hospital is under 60 minutes, there may be no significant benefit to pre-hospital fibrinolysis. Considerations include the following points:

• If protocols are in place for out-of-hospital fibrinolysis and transport time is over 30 minutes, it can be beneficial for EMS to administer fibrinolytics (Class IIa, Evidence level B-R).
• The time from the first interaction with providers to reperfusion should be under 120 minutes (Class I, Evidence level C-EO).
• If patients with STEMI present by 2 hours from symptom onset, rapid fibrinolysis is preferred over PCI if PCI will take over 60 minutes (Class IIb, Evidence level C-LD).
• If patients with STEMI present between 2 and 3 hours from onset of symptoms, rapid fibrinolysis is equivalent to PCI if PCI will take 60–120 minutes (Class IIb, Evidence level C-LD).
• If patients with STEMI present between 3 and 12 hours from symptom onset, PCI within 120 minutes is preferred over rapid fibrinolysis (Class IIb, Evidence level C-LD).
• If out-of-hospital fibrinolysis is offered, transport to a PCI-equipped facility is preferred due to lower rates of intracranial bleeds (Class IIb, Evidence level B-R).
• Typically, if patients with STEMI present between 12 and 24 hours from symptom onset, fibrinolysis is unlikely to be beneficial unless there is persistent chest pain and ST elevation. Fibrinolysis is not given at > 24 hours from the onset of symptoms.

When administering fibrinolysis outside of the hospital, programs should:

• incorporate use of the fibrinolytic checklist
• use rapid 12-lead ECG for diagnosis
• make sure staff is adept at ACLS
• maintain good communication with the receiving hospital
• have medical oversight with expertise in STEMI
• continuously monitor for quality improvement 

Reperfusion

The options for reperfusion for STEMI patients include mechanical (i.e., PCI) and fibrinolytic therapies, which help restore blood flow to the obstructed artery and minimize cardiac damage and death.

Fibrinolysis is less effective and leads to normal flow in 50–60% of patients, while mechanical therapies restore normal flow to over 90% of STEMI patients. The improved efficacy of mechanical therapies leads to fewer deaths and less recurrence of infarction, thereby reducing progression to cardiogenic shock. It also reduces neurologic complications such as stroke and hemorrhage, and that makes it preferred in the older population and patients with bleeding concerns.

Obstructed Artery Stent Placement

When PCI cannot be done within 90 minutes of presentation, fibrinolysis should be administered if there are no contraindications. If contraindications exist, then PCI is offered even if it is delayed. PCI is also preferred in patients with shock. 

Determining appropriate transfers

EMS needs to determine the best destination for patients with STEMI. Generally, all patients should go to a facility that can administer PCI, and this should be done within 90 minutes from EMS arrival. Studies show that mortality is reduced even further with transport times under 30 minutes.

For patients with massive MI and a high risk for death, the transfer should be to a PCI-equipped facility. For transfers from one hospital to another, the goal should be < 30 minutes. When cardiogenic shock is present, patients will best be treated in facilities with access to a complete range of reperfusion therapies, such as IAPB and surgical reperfusion. This should be done within 3 days of MI onset and 18 hours of shock. 

Care Systems

There must be excellent coordination of care for effective ACS management. This includes integration of the community, EMS, and hospital providers. Following the activation of EMS, early communication with the receiving facility should result in quicker access to the appropriate areas of the hospital (ED, catheterization lab) and level of care (cardiac ICU) for optimal management. The goal should be prompt, effective care with minimal delay to reperfusion. 

ED Evaluation

Once within the ED, a suspected ACS patient should be evaluated within 10 minutes, including the following:

• focused history and exam with lead placement for cardiac monitoring
• 12-lead ECG and IV access
• vital signs and assessment of oxygen saturation 
• completion of fibrinolytic checklist
• blood sample collection to check cardiac biomarkers, electrolytes, coagulation 
• CXR and interpretation within 30 minutes without delaying fibrinolysis

Additionally, patients should receive aspirin, oxygen if O2 saturation is < 90%, nitroglycerin, and morphine if no contraindications. Staff should verify if doses have already been given outside of the hospital. In addition, the following recommendations for care apply:

• Perform angiography on out-of-hospital STEMI patients urgently rather than delaying for admission (Class I, Evidence level B-NR).
• Emergency angiography is recommended in an unstable and comatose patient with likely cardiogenic etiology even when STEMI is not present on ECG (Clas IIa, Evidence level B-NR).
• Angiography can be done following cardiac arrest in both unconscious and awake patients (Class IIa, Evidence level C-LD).
• STEMI patients admitted to a hospital incapable of performing PCI should be immediately transferred to a capable hospital, rather than receiving rapid fibrinolysis (Class I, Evidence level B-R).
• STEMI patients admitted to a hospital incapable of performing PCI who cannot be transferred immediately can receive fibrinolysis with delayed transfer to a hospital capable of performing PCI (Class IIb, Evidence level C-LD).
• Preferably these patients should be transferred between 3 and 6 hours (and as long as 24 hours) after receiving fibrinolytic therapty rather than transporting only those who do not benefit from fibrinolytic therapy (Class IIb, Evidence level B-R).

Surviving STEMI: Four Ds

The most important aspect of surviving STEMI is rapid reperfusion to improve blood flow and minimize the size of the infarct to reduce death and morbidity.

Four areas have been looked at to optimize therapy: door, diagnosis, decisions, and drugs. Delays can occur between any of these areas.

Still, health care responders should aim to keep the entire interval under 30 minutes when planning fibrinolysis (door to drug), and up to 90 minutes when the plan is PCI (door to balloon). 

Based on the AHA STEMI guidelines, PCI is preferred over fibrinolysis when it is available to be given by experienced clinicians within a 2-hour time frame. Otherwise, fibrinolysis should be administered in patients with STEMI when chest pain onset was within the preceding 12 hours, and they cannot receive PCI within 2 hours from access to medical care.

Fibrinolysis Reperfusion should never be delayed to proceed with more diagnostic evaluations such as CXR or laboratory studies unless there is a high likelihood of contraindications such as coagulation disorder or aortic dissection.

Stratifying Risk 

Determining the risk versus the benefits of reperfusion is key to management. Fibrinolysis can precipitate intracranial hypertension (ICH) with increased mortality within the first 24 hours following therapy. For patients receiving PCI, the major risks are hemorrhage and propulsion of distant emboli.

There is a range of treatment decisions to be made in STEMI, but all pathways require risk stratification to improve patient outcomes. Health care responders must use the available information to make the best decision possible for the individual patient. There is no one right answer as, even if a patient is technically within the time window for one therapy, it is vital to evaluate the risks and benefits to ensure the therapy is really in the best interest of the patient.

Research evaluating the reperfusion strategy in STEMI serves as a guideline for the upper limit of the delay that can be associated with PCI before the risks of this strategy no longer outweigh the decision to proceed with fibrinolysis. The research suggests that the time delays for particular patients are the following:

• < 2 hours from onset of symptoms: 94 minutes to PCI
• > 2 hours from onset of symptoms: 190 minutes to PCI
• < 65 years: 71 minutes to PCI
• > 65 years: 155 minutes to PCI
• anterior MI: 115 minutes to PCI
• all other MI: 112 minutes to PCI

Further risk analysis is even more detailed for patients meeting the following parameters:

• Within 2 hours from symptom onset:
  • < 65 years of age – 
    • anterior STEMI: 40 min to PCI
    • all other STEMI: 58 min to PCI
  • > 65 years of age –
    • anterior STEMI: 107 min to PCI
    • all other STEMI: 168 min to PCI

• > 2 hours from symptom onset:
  • < 65 years: 
    • anterior STEMI: 43 min to PCI
    • all other STEMI: 103 min to PCI
  • > 65 years:
    • anterior STEMI: 148 min to PCI
    • all other STEMI: 179 min to PCI

Measuring the ECG

It is vital for responders managing STEMI to be familiar with measuring the ECG and its intervals. Obviously, the evaluation of the ST segment changes is a critical component of this work. STEMI is the most emphasized due to the need for timely intervention.

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Related Video: ST Segment Elevation Explained

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Anterior Wall MI V1 ECG

Determining Frequency of 12-lead ECG

When the first ECG does not provide the diagnosis, patients should have serial ECGs. The frequency of administration is based on healthcare provider expertise. Generally, a repeat ECG should be done within 1 hour from the first. If the ECG does not provide the diagnosis, but there is significant suspicion for STEMI, repeat ECGs at 5- to 10-minute intervals should be obtained, or continuous 12-lead monitoring. 

Dynamic changes in the ECG

When the ECG is repeated often, or monitoring is continuous, dynamic changes can be noted. This includes an appearance or disappearance of ST abnormalities. In this instance, the initial ECG may show ST elevation, whereas in a subsequent evaluation, it is normalized. Decision making should be based on the first abnormal ECG finding, not a normal one. 

Evaluating for a Recent LBBB

A recent-onset LBBB and ACS-type chest pain suggest occlusion of the left coronary artery (LCA) and represent a negative sign. In the case of LBBB, the ST segment is distorted due to a delay in depolarization of the left ventricle, and consequently, ST changes cannot be evaluated accurately. In this case, healthcare providers cannot rely on ST elevation for diagnosis.

Importantly, due to the lack of a standard diagnosis, research shows there may be inconsistency or even worsened outcomes with the use of fibrinolytic therapy in this ACS patient group. This is likely due to a wide range of definitions of chest pain as well as a range of bundle branch block diagnoses, including left, right, or unspecified bundle branch blocks. In these cases, it is useful to have a clinician with significant experience in interpreting ECGs.

When a recent LBBB is suspected, reviewing a previous ECG is extremely helpful but not always available. Healthcare providers must make their best educated guess and weigh risks and benefits without knowing if this is an old or recent-onset LBBB. In this case, the clinical history is weighed heavily, including the severity of chest pain, onset of symptoms, and the patient’s personal risk for ACS. In patients with ACS-consistent chest pain and LBBB, fibrinolytic administration is usually considered appropriate. 

Evaluating for a Recent R BBB

Recent-onset RBBB can also increase complications of acute MI. In this case, ST elevation is usually still evident on ECG, as RBBB affects the end portion of the QRS. Such a patient may have Q waves present. However, RBBB can occasionally distort ST segment changes, and consequently, a patient with RBBB and ACS-consistent chest pain without ST elevation may still be a candidate for reperfusion. 

Biomarker Evaluation in STEMI

Cardiac biomarkers are substances that indicate dying myocytes. Since the release of cardiac biomarkers is a late event—usually hours after the onset of chest pain—they should not be used to guide decision making for reperfusion therapy. In fact, biomarkers may not rise until 6 or 8 hours after the onset of symptoms. Common biomarkers available are creatinine kinase cardiac subform (CK-MB) and the troponins (cTn, cTnT, cTnI, hscTnT)

STEMI Cardiac Markers Timeline

Healthcare responders must evaluate the time since onset of symptoms as well as the patient history, pharmacokinetics, and hospital normal values when evaluating the cardiac biomarker levels in individual patients. In patients with high suspicion for ACS and negative biomarkers at < 6 hours from onset of symptoms, the biomarkers should be repeated at 6–12 hours following symptom onset.

At this time, there is no evidence that these biomarkers are useful outside the hospital or in the inpatient unit. Additionally, other laboratory values that may be elevated, such as D-dimer, beta-natriuretic peptide, C-reactive protein, myoglobin, and others, should not be used for clinical decision making.

Adjunctive Treatments in STEMI

There may be other modalities useful in the management of STEMI. It is important to take the patient’s specific history and utilize the local community and hospital algorithms when making decisions. These alternative treatments are not necessarily used routinely but may be appropriate for the individual patient with STEMI. 

Clopidogrel

This medication is an oral precursor to thienopyridine that leads to irreversible inhibition of platelet aggregation. The mechanism is via blockage of adenosine diphosphate receptors, which is different from the action of aspirin. Research shows benefits for clopidogrel use in STEMI and NSTEMI.

Due to the different mechanisms of action, clopidogrel can be used with aspirin to improve efficacy. 

• ACS patients with elevated biomarkers or ECG changes indicating ischemia had improved outcomes (reduced neurological and cardiac adverse events) when clopidogrel was co-administered with heparin and aspirin by 4 hours following ED presentation. 

• Clopidogrel is also beneficial if given ≥ 6 hours before patients without ST elevation receive PCI.

• In STEMI patients 75 years and younger treated with fibrinolysis, the addition of 300 mg clopidogrel in combination with heparin and aspirin improves morbidity and mortality. Patients had less stroke and infarct size, although there was a slight increase in major bleeding events. 
• In STEMI patients receiving PCI, clopidogrel reduced adverse events, including death. However, this was again in association with a slight increase in major bleeding events.
• The CURE study evaluated over 2,000 patients managed with CABG between 5 and 7 days following clopidogrel therapy. Results showed a modest increase in major bleeding events. In patients who are candidates for coronary artery bypass grafting (CABG), clopidogrel should be withheld for 5 days prior to the procedure.
• For PCI patients, clopidogrel can be administered in prehospital or inpatient setting (Class IIb, Evidence level C-LD). Out-of-hospital administrationg should occur only when there is a specific reperfusion strategy that has been authorized by a medical director, STEMI protocol, or team. 
• Clopidogrel precautions: 
• contraindicated when emergent surgery for three-vessel ACS or MI complications is required
• patients 75 years and over should not get an initial 300–600 mg loading dose

The dosing for clopidogrel in STEMI and NSTEMI is:

• 300–600 mg loading dose in those < 75 years
• 300 mg in those ≤ 75 years who have also received heparin and aspirin 
• 300 mg for patients with contraindications to aspirin

Prasugrel

Like clopidogrel, this is an oral precursor to thienopyridine, which leads to irreversible inhibition of platelet aggregation. Again, like clopidogrel, prasugrel decreases morbidity with STEMI, but there is no similar mortality benefit. Additionally, it also increases the number of major bleeding occurrences when used with PCI in patients with NSTEMI.

Patients  ≥ 75 years who have a history of stroke or TIA and low body weight (below 60 kg) are at increased risk for bleeding with this medication. There is some research suggesting slightly improved morbidity and mortality compared to clopidogrel for STEMI and NSTEMI patients who receive PCI. 

• The dosing of prasugrel is 60 mg PO  then 10 mg as maintenance. This is an appropriate alternative to clopidogrel in patients with either STEMI or NSTEMI at least 12 hours after symptom onset who will get PCI.
• Prasugrel 60 mg is an appropriate alternative to clopidogrel in patients with STEMI < 12 hours from symptom onset who will get PCI.
• Prasugrel is contraindicated for STEMI patients receiving fibrinolysis or NSTEMI patients receiving PCI.
• No research supports prasugrel in ED or outside of the hospital.

Ticagrelor

This is another oral therapy that can be used in place of clopidogrel for STEMI and NSTEMI patients undergoing PCI. For patients < 75 years, the dose should be 180 mg and then 90 mg BID.

Beta-blockers

Beta-blockers have been shown to decrease mortality and morbidity in the hospital for patients not receiving fibrinolysis. This research was done primarily during the time before reperfusion was routine. B-blocker therapy reduces fibrillation and ectopy of the ventricles. For patients managed with fibrinolytics, beta-blockers can minimize the size of infarct and decrease significant acute MI. Additionally, if the therapy is given early in the disease course, there is a reduction in mortality and infarct size.

Beta-blockers are also used IV for NSTEMI patients but increase the risk for shock. New research fails to show long-term benefits in mortality, size, or recurrence of infarct or fatal arrhythmias. IV beta-blockers are often used in the ED based on research showing a benefit for metoprolol in acute MI. However, this is not standard policy and requires stratification of risk. It is likely most beneficial in patients with tachyarrhythmias or significant hypertension. However, there is no long-term survival benefit.

Oral beta-blockers are recommended to be given to all patients with ACS regardless of reperfusion strategy unless there is a contraindication.

Recent research evaluated IV management. The strategy was three doses of IV 5 mg metoprolol in 15 minutes. There was a reduction in death from VF, but there was also an increase in death from shock. Mortality was higher in patients at risk for heart failure. Consequently, caution is advised in heart failure patients who may need an increased heart rate to maintain cardiac output.

In ACS, a useful strategy for beta-blocker use includes: 

• administration within 24 hours for STEMI patients unless there is heart failure, shock, or decreased cardiac output 
• patients unable to receive beta-blockers initially should be reassessed for their appropriateness on discharge
• patients with heart failure should receive beta-blockers that are slowly titrated once they are stable 
• administration for hypertensive patients except for those with heart failure, shock, decreased cardiac output, prolonged PR interval, AV block, asthma, and reactive airway diseases 
• calcium channel blockers have not been shown to be safe for use when beta-blockers are contraindicated or as additional therapy when beta-blockers are maximized

Significant contraindications to the administration of beta-blockers include significant left ventricle failure and pulmonary edema, bradycardia (including  2nd- or 3rd-degree AV block), hypotension, poor perfusion, or reactive airway disease.

Oral beta-blockers are preferable in patients with heart failure, with the knowledge that the dosage may need to be lowered or titrated. With this strategy, patients may also receive ACE inhibitors to reduce mortality over the first 30 days. 

Heparin

Heparin has long been used in the management plan for ACS. It indirectly inhibits thrombin formation and can be used with aspirin and other antiplatelet agents in patients with NSTEMI.

Heparin is an anticoagulant.

Unfractionated Heparin

Unfractionated heparin is an IV medication that is somewhat unpredictable and requires frequent monitoring of activated partial thromboplastin time (aPTT). A side effect is thrombocytopenia due to the activation of platelets. It is easily reversed with protamine. When using in ACS, the dosage is 60 units/kg (maximum 4,000 units) and then an infusion of 12 units/kg/hour (maximum of 1,000 units/hr) for 48 hours. The aPTT should be kept between 50 and 70 seconds.

Low-Molecular-Weight Heparin (LMWH)

LMWH is preferred to unfractionated heparin in the management of STEMI as it improves coronary blood flow and complications are less frequent. However, no benefits were noted in patients treated with PCI. Of note, there is an increased risk of intracranial hemorrhage with LMWH compared to unfractionated heparin in those > 75 years. Clinicians should not switch between the two types of heparin as this can increase bleeding risk. 

In ACS, a useful strategy for heparin use includes:

• Fibrinolysis should be given to patients with STEMI when time from presentation to PCI will be > 2 hours and PCI can be done within 3–24 hours following treatment if indicated. (Class IIb, Evidence level B-R).
• Fibrinolysis immediately followed by PCI is not recommended in STEMI (Class III, Evidence level B-R).
• Unfractionated heparin should be given in or outside the hospital for STEMI patients who will receive PCI (Class IIb, Evidence level B-NR).
• Unfractionated heparin may be given outside of the hospital to STEMI patients with increased bleeding risk (Class IIb, Evidence level B-R). 
• LMWH or unfractionated heparin can be used in STEMI patients who will receive PCI.
• LMWH can be given in the ED instead of unfractionated heparin. In patients < 75 years who are concurrently getting fibrinolytics, a 30 mg IV enoxaparin bolus can be administered, and then 1 mg/kg SC every 12 hours. In patients > 75, only a 0.75 mg/kg dose SC BID should be given (no initial bolus). If chronic kidney disease (clearance < 30 mL/min) 1 mg/kg may be given daily. Unfractionated heparin can be given in patients with kidney disease. 
• Enoxaparin can be given instead of unfractionated heparin outside of the hospital when the indication and protocol otherwise remain the same.
• When a STEMI patient does not receive reperfusion therapy, either LMWH or unfractionated heparin can be used while in the ED.
• Fondaparinux 2.5 mg IV and a repeat daily dose of 2.5 mg given SC can be used in patients with a normal renal function who have been managed with non-fibrin thrombolytics such as streptokinase. It can be used as an alternative to unfractionated heparin for STEMI patients that will receive PCI, but the risk of stent thrombus is increased.

Responders should be vigilant about ensuring correct dosing of heparins as there is an increased risk of both intracranial and generalized bleeding. It is vital to remember that while there are recommendations for dosing and timing of heparins, these dosing schedules may need to be altered for specific patients. The ACC/AHA guidelines for emergency cardiovascular care can serve as a resource.

ACE Inhibitors (ACEI) for ACS

Typically, ACEIs are not used in ACLS. Instead, they are initiated after the patient has stabilized and completed reperfusion. Oral ACEIs can decrease the mortality and morbidity of STEMI. Their benefits are independent of other STEMI treatment and improve outcomes when given in the first 24 hours of symptom onset. There are some contraindications to ACEI, including shock and hypotension, bilateral renal artery stenoses, renal failure, true allergies, or renal dysfunction following ACEI or angiotensin receptor blocker use. The recommendation is ACEI for all STEMI patients with anterior MI, heart failure, or ejection fraction ≤ 40%. ACEI can be also used for other STEMI patients without contraindications.

Statins 

Statins (or HMG-coenzyme A reductase inhibitors) have been used to reduce patient morbidity associated with ACS when received in the first few days following symptom onset. There is no obvious benefit of administration in the ED or outside of the hospital setting. Rather, treatment should begin in the first 24 hours following admission. Additionally, statins should be continued in patients who already take the medications at home to limit mortality and adverse cardiac events.

Glucose, Insulin, and Potassium

Traditionally, it was thought that these three therapies reduced mortality in acute MI. However, recent research indicates this is not the case for STEMI patients. It has been demonstrated that, when STEMI patients present by 12 hours from onset of symptoms, infusion of these three medications in the first 24 hours does not change outcomes in terms of death, arrest, or shock. 

Managing Cardiac Arrhythmias

There is some uncertainty regarding managing ventricular arrhythmia in ACS patients. Associated VF is often the cause of sudden death in acute MI. VF usually occurs within 4 hours of symptom onset but remains a high risk for death for the first 24 hours. Additionally, subsequent VF can occur with heart failure or shock that also leads to later deaths with acute MI.

Fibrinolytic therapy with beta-blockers helps to reduce the risk of VF-associated death. While lidocaine decreases VF, it has not been shown to decrease overall mortality and thus is no longer recommended. Similarly, magnesium is not administered regularly, especially in those also being treated with fibrinolytics. Furthermore, no studies indicate a benefit of routine administration of amiodarone or other antiarrhythmics for preventing VF in ACS patients.