eMedicine Specialties > Emergency Medicine > Cardiovascular
Acute Coronary Syndrome: Treatment & Medication
Updated: Aug 6, 2009
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Treatment
Prehospital Care
Generally, patients transported with chest pain should initially be managed under the assumption that the pain is ischemic in origin. Prehospital interventions should be guided by the nature of the presenting complaint, individual risk factors, and associated symptoms (eg, breathing difficulty, hemodynamic instability, appearance of ectopy). Airway, breathing, and circulation should be rapidly assessed with institution of CPR, ACLS-guided interventions, or other measures as indicated for the unstable patient.
- Obtain intravenous access.
- Administer supplemental oxygen.
- Aspirin (162-325 mg) should be given in the field, chewed and swallowed.
- Administer sublingual or aerosolized nitroglycerin if chest pain is ongoing and is believed to be cardiac in origin.
- Additionally, recently, the AHA has published a statement on integrating prehospital ECGs into care for ACS patients (see AHA Publishes Statement on Integrating Prehospital ECGs Into Care for ACS Patients). Prehospital integration of ECG interpretation, when AMI is present, 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 thrombolysis allows eligible patients to receive thrombolysis 30-60 minutes sooner than if treatment were given in the ED; however, prehospital thrombolysis is still under investigation and has not become a trend due to unproven benefit and due to the increase in availability of percutaneous coronary intervention (PCI) in many medical centers as an alternative to thrombolysis for STEMI.
Emergency Department Care
The ACS spectrum concept is a useful framework for developing therapeutic strategies. Antithrombin therapy and antiplatelet therapy should be administered to all patients with an ACS regardless of the presence or the absence of ST-segment elevation. Patients presenting with persistent ST-segment elevation are candidates for reperfusion therapy (either pharmacological or catheter based) to restore flow promptly in the occluded epicardial infarct-related artery. Patients presenting without ST-segment elevation are not candidates for immediate pharmacological reperfusion but should receive anti-ischemic therapy and PCI when appropriate. "Time is myocardium" is a dictum to be remembered as survival has been shown to correlate with time to reperfusion in patients with acute MI. Many centers set goals for, and routinely record, door-to-ECG, door-to-needle (thrombolytic therapy), or door-to-vascular access (for patients receiving PCI) times as measures of quality of care provided.
Rathore et al found that any delay in primary percutaneous coronary intervention after a patient with ST-elevation myocardial infarction (STEMI) arrives at hospital is associated with higher mortality.3 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%, P<0.001). 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.
A recent study by Ryan et al sought to determine if point-of-care cardiac marker testing decreased length of stay in patients being evaluated for acute coronary syndrome in the ED.4 Patients were randomized to 2 groups, with 1000 patients in each group: one having point-of-care markers and central laboratory markers and one having central laboratory markers only. Median time to discharge home was 4.6 hours (3.5-6.1 h) in central laboratory only patients and 4.5 hours (3.5-6.1 h) in the point-of-care patients.
Median time to transfer to an inpatient setting for admitted patients was 5.5 hours (4.2-7.5 h) in the central laboratory patients, and 5.4 hours (4.1-7.3 h) in point-of-care group patients. Time to transfer to the floor was reduced in the point-of-care group at one site, compared with the laboratory group (difference in medians 0.45 h; 95% confidence interval [CI] -0.14 to 1.04 h). Time to ED departure for discharged patients was higher in the point-of-care group than in the laboratory group (difference in medians 1.25 h; 95% CI 0.13 to 2.36 h) at one site.4
Results between the EDs varied, with one showing that point-of-care testing decreased time to admission, and another showing that point-of-care testing increased time to discharge. Ryan et al concluded that the potential effects of point-of-care testing in the ED for patient throughput should be considered in the full context of ED operations.
- Goals of ED care are rapid identification of patients with STEMI, exclusion of alternative causes of nonischemic chest pain, and stratification of patients with acute coronary ischemia into low- and high-risk groups.
- Obtain intravenous access, administer supplemental oxygen, and provide telemetry monitoring if these procedures have not already been accomplished in the prehospital phase. In addition, obtain a 12-lead ECG as soon as possible after arrival.
- Complete a history and physical examination, with focus on risk factors for coronary ischemia; onset, duration, and pattern of symptoms; and early identification of complications of myocardial ischemia (eg, new murmurs, CHF).
- Perform frequent reassessment of vital signs and symptoms in response to administered therapies.
- Serial ECGs and continuous ST-segment monitoring may be useful.
- Many EDs have an observation unit that may be an appropriate disposition for patients who meet admission criteria.
- Medical therapy, as discussed in Medication, is indicated.
Treatment and evaluation guidelines are available from various sources including the American College of Emergency Physicians, American College of Chest Physicians, and National Academy of Clinical Biochemistry.5,6,7
Consultations
Cardiology or interventional cardiology consultation may be indicated for patients with any of the following:
- STEMI - Depending on the center, the patient may be a candidate for PCI, and immediate interventional cardiology consultation is indicated.
- Ongoing symptoms highly suggestive of acute coronary ischemia and nondiagnostic ECG (eg, left bundle-branch block [LBBB])
- Ongoing symptoms refractory to aggressive medical therapy
- Hemodynamic instability
- Evidence of acute valvular dysfunction
- Shock
- Known severe aortic stenosis and ongoing symptoms
- Uncertainty of the diagnosis
The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial studied the impact of age on outcomes in moderate- and high-risk non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Outcomes were analyzed at 30 days and 1 year in 4 age groups, overall and among those undergoing percutaneous coronary intervention (PCI). Of 13,819 patients in the ACUITY trial, 3,655 (26.4%) were younger than 55 years of age, 3,940 (28.5%) were aged 55-64 years, 3,783 (27.4%) were aged 65-74 years, and 2,441 (17.7%) were 75 years or older. Older patients had more cardiovascular risk factors and had a higher acuity at presentation. Patients aged 75 years or older treated with bivalirudin alone had similar ischemic outcomes but significantly lower rates of bleeding compared with those treated with heparin and glycoprotein IIb/IIIa inhibitors overall and in the PCI subset.8
Medication
The goals of treatment are to preserve patency of the coronary artery, augment blood flow through stenotic lesions, and reduce myocardial oxygen demand. All patients should receive antiplatelet agents, and patients with evidence of ongoing ischemia should receive aggressive medical intervention until signs of ischemia, as determined by symptoms and ECG, resolve.
Antiplatelet agents
These agents inhibit the cyclooxygenase system, decreasing the level of thromboxane A2, which is a potent platelet activator. Antiplatelet therapy has been shown to reduce mortality rates by reducing the risk of fatal strokes and fatal myocardial infarctions.
Aspirin (Anacin, Ascriptin, Bayer Aspirin)
Early administration of aspirin in patients with AMI may reduce cardiac mortality in first month.
Adult
160-324 mg PO or chewed; suppository if patient is unable to take PO medications
Pediatric
Not established
Effects may decrease with antacids and urinary alkalinizers; corticosteroids decrease salicylate serum levels; additive hypoprothrombinemic effects and increased bleeding time may occur with coadministration of anticoagulants; may antagonize uricosuric effects of probenecid and increase toxicity of phenytoin and valproic acid; doses >2 g/d may potentiate glucose-lowering effect of sulfonylurea drugs
Documented hypersensitivity; liver damage; hypoprothrombinemia; vitamin K deficiency; bleeding disorders; asthma; children (<16 y) with flu (because of association of aspirin with Reye syndrome)
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
May cause transient decrease in renal function and aggravate chronic kidney disease; avoid use in severe anemia, in history of blood coagulation defects, or in patients taking anticoagulants
Nitrates
These agents oppose coronary artery spasm and reduce myocardial oxygen demand by reducing both preload and afterload.
Nitroglycerin (Nitro-Bid)
Causes relaxation of the vascular smooth muscle via stimulation of intracellular cyclic guanosine monophosphate production, causing a decrease in blood pressure.
Adult
400 mcg SL or spray q5min, repeated up to 3 times
If symptoms persist, administer 5-10 mcg/min IV infusion
Dose should be titrated to reduce MAP by 10%, relieve symptoms, limit adverse effects of hypotension (>30% reduction in MAP or <90 mm Hg systolic), or relieve intolerable headache
Pediatric
Not established
Aspirin may increase nitrate serum concentrations; marked symptomatic orthostatic hypotension may occur with coadministration of calcium channel blockers (dose adjustment of either agent may be necessary)
Documented hypersensitivity; severe anemia; shock; postural hypotension; head trauma; closed-angle glaucoma; cerebral hemorrhage
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in coronary artery disease and low systolic blood pressure
Analgesics
These agents reduce pain, which decreases sympathetic stress, in addition to providing some preload reduction.
Morphine sulfate (Duramorph, Astramorph, MS Contin)
DOC for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of reversibility with naloxone.
Morphine sulfate administered IV may be dosed in a number of ways and commonly titrated until desired effect obtained.
Adult
2-4 mg IV q5-15min; titrate to symptomatic relief or adverse effects (eg, lethargy, hypotension, respiratory depression)
Pediatric
Not established
Phenothiazines may antagonize analgesic effects of opiate agonists; tricyclic antidepressants, MAOIs, and other CNS depressants may potentiate adverse effects of morphine
Documented hypersensitivity; hypotension; potentially compromised airway in which establishing rapid airway control would be difficult
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hypotension, respiratory depression, nausea, emesis, constipation, and urinary retention; caution in atrial flutter and other supraventricular tachycardias; has vagolytic action and may increase ventricular response rate
Anticoagulants
These agents are used to prevent recurrence of clot after a spontaneous fibrinolysis.
Heparin
Augments activity of antithrombin III and prevents conversion of fibrinogen to fibrin. Does not actively lyse but is able to inhibit further thrombogenesis. Prevents recurrence of a clot after spontaneous fibrinolysis.
Adult
80 U/kg IV bolus, followed by an infusion of 18 U/kg/h
Pediatric
Not established
Digoxin, nicotine, tetracycline, and antihistamines may decrease effects; NSAIDs, aspirin, dextran, dipyridamole, and hydroxychloroquine may increase heparin toxicity
Documented hypersensitivity; diagnosed subacute bacterial endocarditis; active bleeding; history of heparin-induced thrombocytopenia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Observe for prolonged or excessive bleeding at venipuncture sites; some preparations contain benzyl alcohol as a preservative; benzyl alcohol, used in large amounts, has been associated with fetal toxicity (gasping syndrome); use of preservative-free heparin is recommended in neonates; use with caution in patients with shock or severe hypotension
Beta-adrenergic blockers
These agents have antiarrhythmic and antihypertensive properties as well as ability to reduce ischemia. They minimize the imbalance between myocardial supply and demand by reducing afterload and wall stress. In patients with acute MI, they have been shown to decrease infarct size as well as short- and long-term mortality, which is a function of their anti-ischemic and antiarrhythmic properties.
Metoprolol (Lopressor)
Selective beta1-adrenergic receptor blocker that decreases the automaticity of contractions.
During IV administration, carefully monitor blood pressure, heart rate, and ECG. Goal of treatment is to reduce heart rate to 60-90 beats/min.
Adult
5 mg slow IV infusion q5min; to a maximum dose of 15 mg or desired heart rate
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels of metoprolol, possibly resulting in decreased pharmacologic effects; toxicity of metoprolol may increase with coadministration of sparfloxacin, phenothiazines, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, and contraceptives; metoprolol may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patients closely and withdraw the drug slowly; during IV administration, carefully monitor blood pressure, heart rate, and ECG
Esmolol (Brevibloc)
Excellent drug for use in patients at risk for complications from beta-blockers, particularly reactive airway disease, mild-to-moderate LV dysfunction, and peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect with ability to stop quickly prn.
Adult
Initial maintenance dose: 0.1 mg/kg/min IV; titrate in increments of 0.05 mg/kg/min q10-15min to a total dose of 0.2 mg/kg/min
Optional loading dose: 0.5 mg/kg slow IV infusion
Pediatric
Not established
Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in a decreased pharmacologic effect; conversely, cardiotoxicity of sotalol may increase when coadministered with sparfloxacin, astemizole (recalled from US market), calcium channel blockers, quinidine, flecainide, or contraceptives
Toxicity of sotalol increases when administered concurrently with digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, or catecholamine-depleting agents
Documented hypersensitivity; uncompensated congestive heart failure; bradycardia; cardiogenic shock; AV conduction abnormalities
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not use in cocaine-related ischemia; beta-adrenergic blockade may decrease the signs and symptoms of acute hypoglycemia and the clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; slowly withdraw drug; closely monitor patients
Glycoprotein IIB/IIA inhibitors
Glycoprotein (GP) IIb/IIIa antagonists prevent the binding of fibrinogen, thereby blocking platelet aggregation. Studies to date suggest that as a class, the addition of intravenous GP IIb/IIIa inhibitors to aspirin and heparin improves both early and late outcomes, including mortality, Q-wave MI, need for revascularization procedures, and length of hospital stay.
Currently, IIb/IIIb antagonists in combination with aspirin are considered standard antiplatelet therapy for patients at high risk for unstable angina. Adenosine diphosphate (ADP) antagonists are not considered standard therapy but may be used in patients unable to tolerate aspirin.
Abciximab (ReoPro)
Chimeric human-murine monoclonal antibody. Binds to receptor with high affinity and reduces platelet aggregation by 80%. Inhibition of platelet aggregation persists for up to 48 h after end of infusion.
Abciximab has been approved for use in elective/urgent/emergent percutaneous coronary intervention.
Adult
0.25 mg/kg bolus IV followed by an infusion of 0.125 mcg/kg/min; maximum 10 mcg/min for 12 h
Pediatric
Not established
Toxicity increases with coadministration of anticoagulants, antiplatelets, and thrombolytics
Documented hypersensitivity; bleeding diathesis; thrombocytopenia (>100,000 cells/mcL); recent trauma; intracranial tumor and/or hemorrhage; severe uncontrolled hypertension; history of vasculitis; cerebrovascular accident within 2 y; active internal bleeding; intracranial hemorrhage; hemorrhagic stroke; severe HTN (systolic BP >200 mm Hg, or diastolic BP >110 mm Hg); major surgical procedure within the past month
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Bleeding complications may occur in patients <75 kg, >65 y, with history of GI disease, or recently received thrombolytic therapy; severe thrombocytopenia may occur within first 24 h of use
Patients receiving other drugs that affect hemostasis (eg, thrombolytics, NSAIDs, dipyridamole, ticlopidine, clopidogrel)
Eptifibatide (Integrilin)
Antagonist of the platelet GP IIb/IIIa receptor, which reversibly prevents von Willebrand factor, fibrinogen, and other adhesion ligands from binding to the GP IIb/IIIa receptor. End effect is the inhibition of platelet aggregation. Effects persist over duration of maintenance infusion and are reversed when infusion ends.
Adult
Unstable angina: 180 mcg/kg IV bolus, followed by a continuous infusion of 2 mcg/kg/min until discharge or surgery
Patients undergoing PCI: 135 mcg/kg IV bolus; administer before PCI, followed by a continuous infusion of 0.5 mcg/kg/min
Pediatric
Not established
When used with heparin and aspirin, an increase in bleeding, compared with using heparin and aspirin alone, can occur
If using concurrently with other drugs that affect hemostasis (eg, warfarin), closely monitor patients
Documented hypersensitivity; severe hypertension (SBP >200 mm Hg); active internal bleeding; history of intracranial hemorrhage; intracranial neoplasm, arteriovenous malformation, or aneurysm; acute pericarditis; bleeding diathesis; trauma or stroke within previous 30 d; platelet count <100,000/mm3; history of thrombocytopenia following exposure to this product
Also contraindicated if serum creatinine level >2 mg/dL (for 180-mcg/kg bolus and 2-mcg/kg/min infusion) or >4 mg/dL (for 135-mcg/kg bolus and 0.5-mcg/kg/min infusion)
History of bleeding diathesis within 30 d; intracranial hemorrhage; history of hemorrhagic stroke; severe HTN (systolic BP >200 mm Hg, or diastolic BP >110 mm Hg); major surgical procedure within the past month
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Most common complications encountered during therapy with eptifibatide are bleeding events; caution in patients with a platelet count <150,000/mm3 and in hemorrhagic retinopathy; because agent inhibits platelet aggregation, caution when using concurrently with drugs that affect hemostasis (eg, thrombolytics, ticlopidine, NSAIDs, warfarin, dipyridamole, clopidogrel); measure activated clotting time (ACT) and maintain aPTT between 50-70 s unless PCI needs to be performed; maintain ACT between 300-350 s during PCI; if platelets decrease to <100,000/mm3, additional platelet counts should be obtained to exclude possibility of pseudothrombocytopenia; if thrombocytopenia confirmed, discontinue GP IIb/IIIa inhibitors and heparin and appropriately monitor and treat the condition; to monitor unfractionated heparin, monitor aPTT 6 h after start of heparin infusion and adjust to maintain aPTT higher than twice the baseline level
Tirofiban (Aggrastat)
Nonpeptide antagonist of GP IIb/IIIa receptor. Reversible antagonist of fibrinogen binding. When administered IV, more than 90% of platelet aggregation inhibited.
Approved for use in combination with heparin for patients with unstable angina who are being treated medically and for those undergoing PCI.
Adult
0.4 mcg/kg/min IV for 30 min; continue at 0.1 mcg/kg/min
Dose should be halved in patients with severe renal insufficiency (CrCl <30 mL/min)
Pediatric
Not established
When used with heparin and aspirin, an increase in bleeding, compared with using heparin and aspirin alone, can occur
If using concurrently with other drugs that affect hemostasis (eg, warfarin), closely monitor patients
Documented hypersensitivity; severe hypertension (SBP >200 mm Hg); active internal bleeding; history of intracranial hemorrhage, intracranial neoplasm, arteriovenous malformation, or aneurysm; acute pericarditis; bleeding diathesis; trauma or stroke within the previous 30 d; platelet count <100,000/mm3; history of thrombocytopenia following exposure to this product
Also contraindicated if serum creatinine level >2 mg/dL (for 180-mcg/kg bolus and 2-mcg/kg/min infusion) or >4 mg/dL (for 135-mcg/kg bolus and 0.5-mcg/kg/min infusion)
History of bleeding diathesis within 30 d; intracranial hemorrhage; a history of hemorrhagic stroke; severe HTN (systolic BP >200 mm Hg, or diastolic BP >110 mm Hg); major surgical procedure within the past month
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Most common complications in therapy with tirofiban are bleeding events; caution in patients with platelet counts <150,000/mm3 and in patients with hemorrhagic retinopathy
Before treating, monitor platelet counts, serum creatinine level, hemoglobin, hematocrit, and PT/aPTT within 6 h after loading infusion and at least daily thereafter (more frequently if evidence suggests significant decline)
Because these agents inhibit platelet aggregation, caution when using concurrently with drugs that affect hemostasis (eg, thrombolytics, ticlopidine, NSAIDs, warfarin, dipyridamole, clopidogrel)
Measure ACT and maintain aPTT between 50-70 s unless PCI needs to be performed; maintain ACT between 300-350 s during PCI; if platelet count decreases to <100,000/mm3, obtain additional platelet counts to exclude pseudothrombocytopenia; if thrombocytopenia is confirmed, discontinue GP IIb/IIIa inhibitors and heparin and appropriately monitor and treat the condition
To monitor unfractionated heparin, monitor aPTT 6 h after beginning heparin infusion; adjust to maintain aPTT higher than 2 times baseline
Low molecular weight heparins
Low molecular weight heparin (enoxaparin) has been shown to reduce cardiac ischemic events and death by as much as 15% in patients with unstable angina. The benefits appear to be sustained at 1 year, with a 13% reduction in patients requiring coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA) and a 15% reduction in death or AMI. These clinical effects have been reported with all patients also receiving aspirin.
One systematic review comparing low molecular weight heparin (LMWH) with unfractionated heparin found no significant difference in benefits between the two. The advantages of using LMWH over unfractionated heparin are ease of administration, absence of need for anticoagulation monitoring, safety profile, and potential for overall cost savings. Although 3 LMWHs are approved for use in the United States, only enoxaparin is currently approved for use in unstable angina. Lev et al found that the combination of eptifibatide with enoxaparin appears to have a more potent antithrombotic effect than that of eptifibatide and unfractionated heparin (UFH).9Enoxaparin (Lovenox)
LMWH is produced by partial chemical or enzymatic depolymerization of UFH. Binds to antithrombin III, enhancing its therapeutic effect. The heparin-antithrombin III complex binds to and inactivates activated factor X (Xa) and factor II (thrombin). LMWH differs from unfractionated heparin by having a higher ratio of antifactor Xa to antifactor IIa compared with UFH. Maximum antifactor Xa and antithrombin activities occur 3-5 h after administration.
Indicated for treatment of acute ST-segment elevation myocardial infarction (STEMI) managed medically or with subsequent percutaneous coronary intervention (PCI). Also indicated as prophylaxis of ischemic complications caused by unstable angina and non-Q-wave MI.
Adult
Treatment regimens include aspirin (75-325 mg/d) if not contraindicated
NSTEMI
1 mg/kg SC q12h
CrCl <30 mL/min: 1 mg/kg SC qd
STEMI
<75 years: 30 mg IV single bolus plus 1 mg/kg SC, then 1 mg/kg SC q12h; not to exceed 100 mg/dose for first 2 SC doses
<75 years and CrCl <30 mL/min: 30 mg IV single bolus plus 1 mg/kg SC, then 1 mg/kg SC qd; not to exceed 100 mg/dose for first 2 SC doses
>75 years: 0.75 mg/kg SC q12h (no initial IV bolus administered), not to exceed 75 mg/dose for first 2 doses
>75 years and CrCl <30 mL/min: 1 mg/kg SC qd (no initial IV bolus administered)
With PCI: If last enoxaparin dose administered >8 h before balloon inflation, administer an additional IV bolus of 0.3 mg/kg
With thrombolytic agent: Give dose specified for age and renal function between 15 min before and 30 min after the start of fibrinolytic therapy
Pediatric
Not established
Platelet inhibitors or oral anticoagulants (eg, dipyridamole, salicylates, aspirin, NSAIDs, sulfinpyrazone, ticlopidine) may increase risk of bleeding
Documented hypersensitivity; major bleeding; thrombocytopenia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
If thromboembolic event occurs despite LMWH prophylaxis, discontinue drug and initiate alternate therapy; elevation of hepatic transaminase levels may occur but is reversible; heparin-associated thrombocytopenia may occur with fractionated LMWHs; 1 mg of protamine sulfate will reverse effect of approximately 1 mg of enoxaparin if significant bleeding complications develop; obtain hemostasis at puncture site before sheath removal after PCI
Direct thrombin inhibitors
Hirudin is the prototype of direct thrombin inhibitors. Hirudin binds directly to the anion binding site and the catalytic sites of thrombin to produce potent and predictable anticoagulation.
Hirudin (Lepirudin, Refludan)
When compared with unfractionated heparin in unstable angina trials, hirudin demonstrated a modest short-term reduction in the composite end point of death or nonfatal MI. Risk of bleeding is increased modestly. Currently, hirudin is indicated only in patients unable to receive heparin because of heparin-induced thrombocytopenia.
Adult
0.4 mg/kg IV bolus over 15-20 s, followed by a continuous infusion of 0.15 mg/kg/h; goal is to increase aPTT 1.5-2.5 times the control; adjust dosing in renal impairment
Pediatric
Not established
Intracranial bleeding may be life threatening following concomitant thrombolytic therapy with rtPA or streptokinase
Documented hypersensitivity
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Associated with an increased need for transfusion (compared with unfractionated heparin) and increased risk of intracranial hemorrhage; no specific antidote exists; if life-threatening bleeding occurs, stop administration, determine coagulation profiles, send T/S, and prepare for blood transfusion
Bivalirudin (Angiomax)
Synthetic analogue of recombinant hirudin. Inhibits thrombin. Used for anticoagulation in unstable angina undergoing PTCA. With provisional use of glycoprotein IIb/IIIa inhibitor (GPIIb/IIIa inhibitor) indicated for use as anticoagulant in patients undergoing PCI. Potential advantages over conventional heparin therapy include more predictable and precise levels of anticoagulation, activity against clot-bound thrombin, absence of natural inhibitors (eg, platelet factor 4, heparinase), and continued efficacy following clearance from plasma (because of binding to thrombin).
Adult
0.75 mg/kg IV bolus initially; followed by 1.75 mg/kg/h IV for duration of procedure or up to 4 h
Pediatric
Not established
Clinical trials have shown that patients undergoing PTCA/PCI, coadministration of bivalirudin with heparin, warfarin, or thrombolytics may increase risks of major bleeding events compared with patients not receiving these medications concomitantly
Documented hypersensitivity; cerebral aneurysm; intracranial hemorrhage, general uncontrollable hemorrhage, or active major bleeding
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Caution in renal impairment (dose only needs adjustment in patients with severe renal impairment of CrCl <30 mL/min and patients who are hemodialysis dependent), recent surgery or trauma, GI ulceration; risk of bleeding; may cause back pain, nausea, headache, hypotension
Adenosine diphosphate receptor antagonists
Two thienopyridines, clopidogrel and ticlopidine, are ADP antagonists that are approved for antiplatelet activity. Both have irreversible antiplatelet activity but take several days to manifest. A potential additive benefit exists when ADP antagonists are used in conjunction with aspirin.
These drugs may be considered alternatives to aspirin in patients intolerant or allergic to aspirin.
Clopidogrel (Plavix)
Generally preferred over ticlopidine because it more rapidly inhibits platelets and appears to have a more favorable safety profile.
Adult
300 mg PO loading dose, followed by 75 mg PO qd
Pediatric
Not established
Safety of concomitant use of heparin not established; coadministration with NSAIDS is associated with increased gastrointestinal bleeding
Documented hypersensitivity; active bleeding; peptic ulcer or CNS hemorrhage
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
TTP has been reported rarely after use of Plavix; caution in patients at risk of bleeding from trauma, surgery, or other pathological conditions; caution in prolonged bleeding time or liver disease
Ticlopidine (Ticlid)
Beneficial effects were noted in patients with UA after 2 wk of use in one randomized trial. When compared to controls, ticlopidine use decreased vascular deaths and nonfatal MIs.
Adult
250 mg PO bid
Pediatric
Not established
Effects may decrease with coadministration of corticosteroids and antacids; toxicity increases when taken concurrently with theophylline, cimetidine, aspirin, and NSAIDS
Documented hypersensitivity; presence of neutropenia or thrombocytopenia or past history of either TTP or aplastic anemia; hemostatic disorder or active bleeding; severe liver impairment
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Discontinue if absolute neutrophil count decreases to <1200 per mm3 or if platelet count falls to <80,000 per mm3; GI adverse effects include diarrhea, abdominal pain, nausea, and vomiting; may cause neutropenia, which usually reverses within 1-3 wk of discontinuation of therapy
More on Acute Coronary Syndrome |
| Overview: Acute Coronary Syndrome |
| Differential Diagnoses & Workup: Acute Coronary Syndrome |
 Treatment & Medication: Acute Coronary Syndrome |
| Follow-up: Acute Coronary Syndrome |
| Multimedia: Acute Coronary Syndrome |
| References |
| Further Reading |
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References
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Koller A. Exercise-induced increases in cardiac troponins and prothrombotic markers. Med Sci Sports Exerc. Mar 2003;35(3):444-8. [Medline].
[Best Evidence] Rathore SS, Curtis JP, Chen J, Wang Y, Nallamothu BK, Epstein AJ, et al. Association of door-to-balloon time and mortality in patients admitted to hospital with ST elevation myocardial infarction: national cohort study. BMJ. May 19 2009;338:b1807. [Medline].
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Further Reading
Clinical guidelines
Clinical policy: critical issues in the evaluation and management of adult patients with non-ST-segment elevation acute coronary syndromes.Fesmire FM, Decker WW, Diercks DB, Ghaemmaghami CA, Nazarian D, Brady WJ, Hahn S, Jagoda AS, American College of Emergency Physicians. Clinical policy: critical issues in the evaluation and management of adult patients with non-ST-segment elevation acute coronary syndromes. Ann Emerg Med 2006 Sep;48(3):270-301 Antithrombotic therapy for non-ST-segment elevation acute coronary syndromes. American College of Chest Physicians evidence-based clinical practice guidelines (8th edition).Harrington RA, Becker RC, Cannon CP, Gutterman D, Lincoff AM, Popma JJ, Steg G, Guyatt GH, Goodman SG. Antithrombotic therapy for non-ST-segment elevation acute coronary syndromes: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008 Jun;133(6 Suppl):670S-707S.
Use of cardiac biomarkers for acute coronary syndromes. Laboratory medicine practice guidelines: evidence-based practice for point-of-care testing. Storrow AB, Apple FS, Wu AH, Jesse R, Francis G, Christenson RH. Use of cardiac biomarkers for acute coronary syndromes. In: Laboratory medicine practice guidelines: evidence-based practice for point-of-care testing. Washington (DC): National Academy of Clinical Biochemistry (NACB); 2006. p. 13-20.Keywords
acute coronary syndrome, ACS, ACS treatment, ACS causes, ACS symptoms, ST-elevation myocardial infarction, STEMI, non-ST-elevation myocardial infarction, NSTEMI, ACS, angina, myocardial ischemia, acute myocardial ischemia, myocardial infarction, MI, coronary artery disease, coronary heart disease, heart disease, chest pain
atherosclerotic plaques, variant angina, Prinzmetal angina, coronaryvasospasm, stable angina, unstable angina, hypertension, diabetes mellitus, smoking, hypercholesterolemia, hyperlipidemia
