All patients suspected of having cardiac pain should be placed on a cardiac monitor, receive an intravenous line, and supplemental oxygen. Dysrhythmias should be treated if their effect on heart rate exacerbates oxygen supply/demand imbalance, or if the dysrhythmia seems capable of electrical deterioration (eg, to a nonperfusing rhythm; see Chapter 2). The process of risk stratification using tools such as the TIMI Risk Score should be rapidly undertaken.
Aspirin should be administered in a dose of 160 to 325 milligrams (chewed) in patients with suspected ACS, unless contraindicated or already taken by the patient.
Oral and transdermal nitroglycerin (NTG) are useful in treating angina. A sublingual dose should be repeated twice, for a total of 3 tablets, administered at 2 to 5 min intervals. If there is no improvement with sublingual NTG, intravenous NTG should be started at 5 to 10 micrograms/min. IV NTG is recommended for MI or recurrent ischemia. The dose should be adjusted by 5 to 10 micrograms/min increments every 3 to 5 min, titrated to pain level and blood pressure reduction up to 200 micrograms/min maximum. NTG should be used cautiously in the setting of borderline-low blood pressure, as hypotension may worsen ischemia. NTG is contraindicated in the setting of RV infarction, due to risk of hypotension related to loss of preload. A common side effect of NTG is headache.
Morphine sulfate can be used if there is uncontrolled ischemic chest discomfort despite NTG. Morphine may decrease cardiac output, and should be used with caution in the presence of hypotension, and in patients with inferior MI.
The thienopyridine clopidogrel, when added to ASA, reduces the composite risk of cardiovascular death, MI, or stoke. Thienopyridines bind to the ADP receptor and inhibit platelet aggregation. Clopidogrel should be considered in addition to standard care (ASA, anticoagulants) for patients with moderate to high-risk NSTEMI and STEMI, and in patients in whom PCI is planned. Clopidogrel is used without aspirin in patients allergic to aspirin. Clopidogrel increases risk of bleeding, and should be withheld at least 5 days before coronary artery bypass grafting (CABG). Prasugrel is an oral thienopyridine prodrug with no current indications for ED use.
Unfractionated heparin (UFH) is used for its anticoagulant properties. UFH has several disadvantages, including (1) the need for IV administration, (2) the requirement for frequent monitoring of the activated partial thromboplastin time (aPTT), (3) an unpredictable anti-coagulant response in individual patients, (4) heparin-induced thrombocytopenia (HIT), and (5) increased risk of bleeding. Anticoagulation due to UFH can be reversed with protamine. The dosage is 1 milligram of protamine per 100 U of UFH infused in the previous 4 hours.
As compared to UFH, low molecular weight heparins (LMWH) offer greater bioavailability, lower protein binding, longer half-life, improved safety, and more reliable anticoagulant effect. They are administered in fixed subcutaneous doses and do not require laboratory monitoring. As compared to UFH, LMWH administration for ACS is associated with decreased ischemia and MI although there is an increase in minor bleeding complications. For patients with UA/NSTEMI, enoxaparin (a LMWH) or UFH are both reasonable choices for patients undergoing PCI revascularization. Improved outcomes are demonstrated with consistent therapy (use of a single antithrombin from the ED through the catheterization laboratory) and increased bleeding is seen when patients are switched from one antithrombin to another. In patients in whom CABG is planned, LMWH should be avoided (due to its half-life) in favor of UFH. In patients > 75 years of age, enoxaparin must be used with caution due to an increased risk of ICH. Enoxaparin dosing adjustments are recommended in patients with impaired renal function (creatinine clearance < 30 mL/min).
Factor Xa inhibitors such as fondaparinux, a synthetic pentasaccharide, have similar efficacy to UFH in patients with UA/NSTEMI; bleeding risk is lower than that with enoxaparin. Current ACC/AHA guidelines consider fondaparinux an option as an antithrombin. In STEMI patients lacking renal impairment, fondaparinux may be considered for those patients treated with thrombolytics that are not fibrin specific (ie, streptokinase).
Direct thrombin inhibitors bind directly to thrombin in clot and are resistant to agents that degrade heparin. Comparison of bivalirudin with UFH found no outcomes benefit in NSTEMI patients, but less bleeding occurred and no dosage adjustment is required in renal impairment. For patients with STEMI, bivalirudin may be considered as an alternative to UFH and GP IIb/IIIa inhibitors.
Percutaneous coronary intervention (PCI), coronary angioplasty with or without stent placement, is the treatment of choice for the management of STEMI when PCI can be performed within 90 min of initial ED presentation. PCI may be offered to patients presenting to a non-PCI facility when prompt transfer can result in acceptable door-to-balloon times. Early invasive therapy (PCI) within 48 hours is recommended in high-risk patients with UA/STEMI, in patients with recurrent angina/ischemia, and in those who have elevated troponin, new or presumably new ST-segment depression, or high risk findings on stress testing. PCI is also more likely to be beneficial in the setting of depressed LV function, hemodynamic instability, sustained ventricular tachycardia, PCI within the previous 6 months, or prior CABG.
In treatment settings without timely access to PCI, fibrinolytics are indicated for patients with STEMI if time to treatment is < 6 to 12 hours from symptom onset, and the ECG has at least 1 mm ST-segment elevation in two or more contiguous leads. The dosages of individual fibrinolytic agents are listed in Table 18-2. STEMI patients who have received fibrinolytics should receive full-dose anticoagulants, started in the ED and maintained for a minimum of 48 hours. Similar efficacy and safety profiles have been demonstrated for tPA, rtPA, and TNK. Contraindications for fibrinolytics are listed in Table 18-3. Before administering thrombolytics, informed consent should be obtained (with particular attention paid to an understanding of the risks). Arterial puncture should be avoided, as should venipuncture or central line placement in areas which are not readily compressible.
Tissue plasminogen activator (tPA) is a naturally occurring human protein and is not antigenic. tPA is fibrin-specific and has a half-life of 5 min. When compared with traditional dosing, front-loaded tPA has been shown to have superior 90 min patency rates and reocclusion rates, with no increase in bleeding risk.
Reteplase (rPA) is a nonfibrin-specific deletion mutant of tPA with a prolonged half-life of 18 min (as compared to tPA's half-life of 3 min). Reteplase may have a faster time to perfusion. The main advantage of reteplase is that it is given as a (double) bolus rather than infusion.
Tenecteplase (TNK) is a fibrin-specific substitution mutant of tPA that is given as a single weight-based bolus.
Streptokinase (SK) activates circulating plasminogen, is not fibrin-specific, and is capable of generating an allergic reaction (minor: 5% to 5.7%, anaphylaxis: <0.2% to 0.7%). Hypotension occurs in up to 15% of patients and is usually responsive to fluids and slowing of SK infusion. Contraindications to SK include hypotension, prior SK administration (within 6 months), and streptococcal infection within a year. SK's half-life is 23 min, but systemic fibrinolysis persists for 24 hours. Heparin must be given within 4 hours of starting SK.
The most significant complication of thrombolytics is hemorrhage, particularly ICH. Significant bleeding, especially internal, requires cessation of thrombolytics, heparin, and aspirin. Crystalloid and red blood cell infusion may be necessary. Cryoprecipitate (cryo) and fresh frozen plasma (FFP) may be used in an attempt to reverse fibrinolysis due to thrombolytics. Initially, 10 U of cryo are given, and fibrinogen levels are obtained. If the fibrinogen level is <1 gram/L, the dose of cryo should be repeated. If bleeding continues despite a fibrinogen > gram/L, or if the fibrinogen level is <1 gram/L after 20 U of cryo, then 2 U of FFP should be administered. If this does not control hemorrhage, then platelets or antifibrinolytic agents (aminocaproic acid or tranexamic acid) are indicated.
Recent evidence shows no particular benefit to the early IV administration of β-blockers on cardiac rhythm, infarct size, reinfarction, or mortality. Oral β-blocker therapy does not need to be initiated in the ED unless there is a specific indication (eg, tachycardia), but β-blockers may be initiated within the first 24 hours of hospitalization for patients lacking contraindications, alternatives include metoprolol and atenolol among others.
Glycoprotein IIb/IIIa (GP IIb/IIIa) antagonists bind to platelets and inhibit their aggregation. Abciximab, eptifibatide, and tirofiban are currently available. There is no current evidence supporting the routine use of GP IIb/IIIa inhibitor therapy prior to angiography in patients with STEMI, and the use of these agents upstream is uncertain. Use of GP IIb/IIIa inhibitors should be guided by local interdisciplinary review of ongoing clinical trials, guidelines, and recommendations.