MEDICAL THERAPY

Initial medical therapy for ACS includes rapid delivery of antiplatelet agents, anticoagulants and revascularization therapy to include fibrinolytic therapy (if no contraindications exist and PCI is not immediately available). The below sections include lists of common available medications in each class.

Antiplatelet Therapy

Aspirin should be administered immediately to all patients with suspected ACS if no contraindications exist. Once the diagnosis of ACS has been made, a platelet adenosine diphosphate receptor (P2Y).12 An inhibitor (e.g., clopidogrel, ticagrelor) should then also be administered if no contraindications exist. Initial dosing for all agents is listed below.

1.Aspirin 162 – 325mg PO x 1 (chewable is preferred, non-enteric coated preferred if chewable not available) then 81mg PO daily.

AND

2. Clopidogrel (Plavix)

Age ≤ 75 years old: initial loading dose of 300mg PO x 1 then 75mg PO daily.

Age > 75 years old: initial dose of 75mg PO x 1 then 75mg PO daily.

OR

3.Ticagrelor (Brilinta) 180mg PO x1 then 90mg twice daily. It is important to note that ticagrelor can cause dyspnea which is thought to be benign, though sometimes concerning to the patient/clinician.

Anticoagulant Therapy

Systemic anticoagulation should be administered as soon as the diagnosis of ACS is made if no contraindications exist. Options for anticoagulants include unfractionated heparin and low molecular weight heparin (LMWH) (i.e. enoxaparin) which exert their anticoagulant properties by indirectly inhibiting thrombin. Another option is factor Xa inhibitor (i.e. fondaparinux). Heparin is administered as a bolus followed by a drip, and its effects are monitored by the activated partial thromboplastin time (aPTT). Currently, typical CCATT that transports patients out of theater do not have the ability to monitor aPTT for heparin drips. Thus, enoxaparin is preferred over a heparin drip when transport is required, given its ease of use. If enoxaparin or another LMWH is not available, then consideration of fondaparinux should be utilized if available. If heparin is the only agent available, then it should be given. Dosing consideration for transport would be decided based on an aPTT immediately prior to the flight. For patients that have a known or suspected history of heparin induced thrombocytopenia, fondaparinux should be used. Anticoagulation should continue for at least 48 hours or until revascularization.

The following are the dosing for each agent listed below:

1. Enoxaparin (Lovenox) – preferred agent

a.STEMI dosing:

- Age < 75 years: single 30mg IV bolus plus 1mg/kg SubQ (maximum 100mg for the first 2 doses only). then 1mg/kg SubQ every 12 hours
- Age ≥ 75 years: 0.75 mg/kg SubQ every 12 hours

b. NSTEMI dosing: 1mg/kg SubQ every 12 hours.

c. Consult pharmacy to adjust this dose if there is any renal injury (rise in creatinine).

OR

2. Heparin Sulfate

a.STEMI dosing: 60 U/kg initial bolus IV (4,000 U maximum), then 12 U/kg/hr (maximum 1,000 u/hr) infusion. Maintain aPTT 1.5–2.0 times control (50-70s).

b.NSTEMI dosing: 60 U/kg initial bolus IV (5,000 U maximum), then 12 U/kg/hr (maximum 1,000 U/hr) infusion. Maintain aPTT 1.5–2.0 times control (50-70s).

OR

3. Fondaparinux (Arixtra)

a. STEMI dosing: 2.5 mg IV x1 then 2.5 mg SubQ daily.

b. NSTEMI dosing: 2.5 mg SubQ daily.

Reperfusion Therapy

Prompt reperfusion is the mainstay of STEMI care. Whenever possible, a patient presenting with STEMI should be transferred emergently to the nearest medical facility that can perform urgent PCI as it is considered the optimal treatment. This should be achieved within 2 hours of patient arrival.13 In the event that door-to-balloon time cannot be achieved within 2 hours, fibrinolytics should be given instead. In the deployed setting, PCI, may be prohibitively far away, and thus rapid delivery of fibrinolytic therapy is the method of choice for revascularization. Fibrinolytic therapy should be administered within 30 minutes of STEMI diagnosis. There are absolute and relative contraindications to administration of fibrinolytics (listed in Appendix A). This list should be meticulously reviewed step by step prior to administration of these agents. The two most common agents available are listed below with their dosing. Fibrinolytics should be offered to patients with symptom duration of 12 hours or less. It is recommended that expert consultation with the theater cardiology consultant be used prior to administering fibrinolytics in the 12 to 24 hour period.

Note: Dual antiplatelet therapy, systemic anticoagulation, beta blocker and high dose statins should still be given even when fibrinolytics are given.

1. Tenecteplase (TNKase) – preferred agent

a. < 60 kg: 30mg IV bolus x 1

b. 60-69 kg: 35mg IV bolus x 1

c. 70-79 kg: 40mg IV bolus x 1

d. 80-89 kg: 45mg IV bolus x 1

e. ≥ 90 kg: 50mg IV bolus x 1

OR

2. Alteplase (Activase)

a. ≤ 67 kg: 15mg IV bolus over 1-2 minutes, then infusion of 0.75 mg/kg (maximum 50mg) over 30 minutes, then infusion of 0.5 mg/kg (maximum 35mg) over 60 minutes.

b. 67 KG: 15mg IV bolus over 1-2 minutes, then infusion of 50mg over 30 minutes, then infusion of 35mg over 60 minutes (maximum total dose 100mg).

Note: I n contrast to STEMI, fibrinolytics are contraindicated in UA/NSTEMI patients.

Statin Therapy

Regardless of the patient’s blood lipid levels, high dose Statin therapy should also be administered during the initial presentation (within the first 2 hours) of ACS. The following are the two therapy options to administer:

1. Atorvastatin (Lipitor) 80mg PO x 1 then 80mg nightly.

OR

2. Rosuvastatin (Crestor) 20-40mg PO x1 then 20-40mg PO daily.

SUPPORTIVE THERAPY

Supplemental Oxygen

Administer ring oxygen in patients with ACS is recommended only when oxygen saturation levels are < 90%, to avoid potential harm from oxygen free radicals and further hyperoxia coronary vasoconstriction.

Analgesia

Decreasing the pain response can block sympathetic activity and relieve anxiety, which decreases myocardial oxygen consumption. The routine use of morphine for pain control is not recommended since this has been shown to increase the risk of mortality in ACS.34 Nitroglycerin a vasodilator, opens blood vessels to improve blood flow; treating angina symptoms, such as chest pain or pressure that happens when there is not enough blood flowing to the heart. Nitroglycerin dilates coronary arteries and relaxes vascular smooth muscles, resulting in decreased preload/afterload and decreased myocardial oxygen demand.

Nitroglycerin

1. Initial dose of 0.3 – 0.4 mg sublingually every 5 minutes for 3 doses; afterwards an intravenous infusion may be considered.
2. If a nitroglycerin IV infusion is administered, start at 5-10 mcg/ minute (min) and titrate as needed to relieve anginal symptoms in increments of 5 mcg/min every 5-10 minutes up to 20 mcg/min; if angina persists at a dose of 20 mcg/min then increase the dosage by 10-20 mcg/min every 3-5 minutes to a maximum dose of 400 mcg/min.
3. Nitroglycerin is contraindicated in patients who have a systolic blood pressure < 100 mmHg, who have used phosphodiesterase inhibitors in the last 24 hours, or who have evidence of inferior STEMI on ECG.

Beta Blockers

Beta blockers block sympathetic stimulation and decrease the heart rate. They have been shown to decrease early development of lethal ventricular dysrhythmias as well as improve long term left ventricular remodeling. Although the American Heart Association and American College of Cardiology recommend that beta blockers be initiated in the first 24 hours of NSTEMI, there have been studies that show early administration of beta blockers in the ED was associated with higher rates of shock or death than later administration.35 Initiate this medication after the patient has been hospitalized in either the Role 2 or Role 3. Beta blockers should be withheld in patients with systolic blood pressure < 100 mmHg, heart rate < 60 beats per minute, evidence of pulmonary edema, second or third degree heart block, severe reactive airway disease, or elevated risk of cardiogenic shock.

1. Metoprolol tartrate (immediate release) – 12.5 mg PO every 6 – 12 hours.

OR

2. Metoprolol succinate (extended release) – 25-50 mg PO once daily.

OR

3. Atenolol – 50-100 mg PO every 12 to 24 hours.

ACE Inhibitors and ARBs

Angiotension converting enzyme (ACE) inhibitors that are initiated within 24 hours to 16 days after an acute MI show improved patient survival as well as improved left ventricular ejection fraction. ACE inhibitors are contraindicated in systolic blood pressure < 100 mmHg, history of bilateral renal artery stenosis, hyperkalemia, or prior worsening renal function with ACE inhibitors. It is reasonable to administer angiotensin receptor blockers (ARBs) in patients who cannot tolerate ACE inhibitors.

1. Captopril - initial dose of 6.25 mg PO, which is increased at 6 to 8 hour intervals to a maximum of 50 mg PO three times daily as long as the systolic blood pressure is above 90 to 100 mmHg.

OR

2. Enalapril - initial dose 2.5 mg PO daily increased up to 20 mg PO twice daily.

OR

3. Lisinopril - initial dose 2.5 mg PO daily increased to a maximum of 10 mg PO daily.

OR

4. Losartan - 25 to 50 mg PO once daily depending on initial blood pressure.

Other Therapies

If indicated continue to utilize Proton pump inhibitors. Nonsteroidal anti-inflammatory drugs (NSAIDs) on the other hand should be avoided in these patients due to their increased risk of adverse cardiovascular events and the increased risk of bleeding when combined with the other mainstay treatments of ACS such as antiplatelet and anticoagulant therapy. Routine use of blood transfusion in the setting of ACS is associated with increased mortality.13,36,37 It is recommended to avoid transfusion unless the hemoglobin level is < 8 g/DL .