| Agent | Mechanism of Action | Dosage | Benefits | Side Effects | Notes |
|---|
| Nitroglycerin | Relaxation of vascular smooth muscle resulting in vasodilation | Begin
with an intravenous bolus of 12.5-25 µg and a pump-controlled infusion
of 10-20 µg/m. Increase dosage by 5-10 µg every 5-10 minutes | Relief of anginal symptoms and improved hemodynamics in congestive heart failure | Headache, hypotension, with particular attention to patient with inferior wall infarctions and possible RV involvement | Titration endpoints are control of symptoms or a decrease in mean arterial pressure by 10%.
Before discharge, patient should be switched to oral nitrates.
Short-acting nitrates include sublingual nitroglycerin that the patient
may use prn for chest pain, and isosorbide dinitrate that can be
started at 5 mg tid and titrated up to a maximum of 60 mg tid. Longer
acting nitrates include isosorbide mononitrate, starting at 30 mg qd,
titrating up to a maximum of 240 mg qd |
| Aspirin | Inhibits platelet aggregation by preventing formation of thromboxane A2 | 160-325 mg/d | Decreased platelet aggregation and development of thrombosis | Gastric irritation, potential bleeding from surgical sites | Should be avoided in patients with known hypersensitivity |
| Antiplatelet agent (clopidogrel,
ticlopidine) | Inhibit adenosine diphosphate-mediated platelet activation | Clopidogrel: 75 mg/d, 300 mg initial dose if percutaneous intervention planned;
Ticlopidine: 250 mg bid, a loading dose of 500 mg can be used if
percutaneous intervention is planned or rapid onset is required | Clopidigrel is preferred over ticlopidine | Diarrhea, abdominal pain, nausea, vomiting, neutropenia in ~2.4% (severe in 0.8%) and rarely, thrombocytopenia purpura | Clopidogrel is preferred as it has a more rapid onset of action and lower side effect profile |
| Unfractionated
heparin
| Enhances activity of antithrombin III to inhibit thrombin activity and generation of anti Xa to anti IIa ratio of 1:1 | Intravenous
infusion: 70 U/kg as a bolus, then maintenance dose of 15 µg/kg·h
adjusted to maintain a PTT at 1.5-2.0 times control for 48 hours
OR
Subcutaneously 7500 U, 2x/daily, patients not treated with
thrombolytics who are at high risk for systemic emboli (IV preferred) | Slight early reduction in mortality and risk of reinfarction | Bleeding, hypersensitivity, heparin-induced thrombocytopenia | Heparin
therapy depends on the thrombolytic agent chosen. Recommended for
intravenous use in patients receiving alteplase and should be started
at the initiation of alteplase infusion; its use with nonselective
agents (streptokinase, anistreplase, urokinase) should be reserved for
patients at risk for systemic emboli.
Two landmark trials
(ESSENCE and TIMI IIB) have shown LMWH to actually be superior to UFH,
however in certain situations UFH may still be appropriate (i.e., a
patient at high risk for bleeding may require UFH due to its short
half-life elimination) |
| Low-molecular-weight heparin (dalteparin,
enoxaparin,
nadroparin,
tinzaparin) | Inhibits thrombin generation; also acts on antithrombin to inhibit factor IIa activity | Varies depending on agent | More effective and safe than UFH.
PTT monitoring not necessary | Bleeding, hypersensitivity, HIT | Less risk of HIT compared to UFH.
Greater bioavailability, more predictable dose-response relationship
compared to UFH. May require dosage adjustment in patients with renal
insufficiency |
| Antiplatelet agent, glycoprotein IIb/IIIa antagonist (Abciximab) | Monoclonal antibody fragment with high affinity for the platelet receptor GP IIb/IIIa causing inhibition of platelet aggregation | 0.25 mg/kg IV bolus over 10-60 min, then 10 µg/min IV x 12 h | Reduction in combined endpoints of death, MI, and refractory ischemia | Bleeding | Abciximab has been shown to be antigenic and the development of antibodies has been reported (90). May require dosage adjustment in patients with renal insufficiency |
| Antiplatelet agent, glycoprotein IIb/IIIa antagonist (Tirofiban) | Peptide that binds IIb/IIIa receptor and inhibits platelet aggregation | IV bolus, 0.4 µg/kg·min x 30 min, then 0.1 µg/kg·min infusion | Reduction in combined endpoints of death, MI, and refractory ischemia | Bleeding | Recovery
of platelet function is more rapid with eptifibatide and tirofiban.
Eptifibatide and tirofiban are more specific for GP IIb/IIIa. May
require dosage adjustment in patients with renal insufficiency |
| Antiplatelet agent, glycoprotein IIb/IIIa antagonist (Eptifibatide) | Non-peptide that binds IIb/IIIa receptor and inhibits platelet aggregation | Load 180 µg/kg IV over 1-2 min then 2 µg/kg·min infusion | Reduction in combined endpoints of death, MI, and refractory ischemia | Bleeding | Recovery
of platelet function is more rapid with eptifibatide and tirofiban.
Eptifibatide and tirofiban are more specific for GP IIb/IIIa. May
require dosage adjustment in patients with renal insufficiency |
| Thrombolytic agent (Alteplase) | Plasminogen activation with lysis of fibrin (and fibrinogen) | IV bolus 15 mg, then 0.75 mg/kg·30 min (maximum, 50 mg), then 0.50 mg/kg·60 min (maximum, 35 mg) | Rapid lysis of clot with reperfusion of infarct-related territory and reduction in mortality | Bleeding, particularly hemorrhagic stroke | Indicated in patients with acute ST-segment elevation or new LBBB MI.
Should be administered with heparin infusion as outlined |
| Thrombolytic agent (Streptokinase) | Plasminogen activation with lysis of fibrin and fibrinogen | 1.5 million units in 30-60 min | Rapid lysis of clot with reperfusion of infarct-related territory and reduction in mortality | Bleeding,
particularly hemorrhagic stroke. The risk of intracranial hemorrhage is
greater with tPA than SK, especially in patients older than age 75.
Hypersensitivity reaction, may be less effective in patients with previous streptococcal infections | Modest but statistically significant benefit of alteplase over streptokinase.
Cannot be administered within 6 months of prior use |
| Thrombolytic agent (Reteplase) | Plasminogen activation with lysis of fibrin and fibrinogen | Initial bolus of 10 U followed by 10 U in 20 min | Rapid lysis of clot with reperfusion of infarct-related territory and reduction in mortality | Bleeding, particularly hemorrhagic stroke | |
| Thrombolytic agent (Tenecteplase) | Plasminogen activation with lysis of fibrin and fibrinogen | 0.53 mg/kg single IV bolus | Rapid lysis of clot with reperfusion of infarct-related territory and reduction in mortality | Bleeding, particularly hemorrhagic stroke | |
| β-blocker (Atenolol) | Decrease heart rate, systemic arterial pressure, and myocardial contractility, thereby decreasing myocardial oxygen demand | 5-10 mg IV, followed by oral 100 mg/d | Prevents subsequent reinfarction and recurrent ischemia, reduces mortality | Excessive
bradycardia, heart block, hypotension, bronchospasm, worsening of
congestive heart failure, worsened diabetic control, worsening of
symptoms of peripheral vascular disease | Beneficial in patients with LV dysfunction if heart failure status is stable |
| β-blocker (Metoprolol) | Decrease heart rate, systemic arterial pressure, and myocardial contractility, thereby decreasing myocardial oxygen demand | 15 mg IV in 3 divided doses followed by 50 mg orally every 6 h x 2 d, then 100 mg bid | Prevents subsequent reinfarction and recurrent ischemia, reduces mortality | Excessive
bradycardia, heart block, hypotension, bronchospasm, worsening of
congestive heart failure, worsened diabetic control, worsening of
symptoms of peripheral vascular disease | Beneficial in patients with LV dysfunction if heart failure status is stable |
| β-blocker (Carvedilol) | Nonselective blockade of α, β1, and β2 adrenergic receptors. Decreases heart rate and systemic arterial pressure; may reduce potentially deleterious LV remodeling | 6.25 mg bid titrated to 25 mg bid over 4-6 weeks | Reduction in mortality and nonfatal MI | Same as for other β-blockers (see above) | Beneficial when initiated 3-21 days after MI in stable patients with left ventricular ejection fraction  40% |
| ACE inhibitor (Captopril) | Reduces potentially deleterious LV remodeling | 6.25-50 mg tid | Reduction in mortality | Hypotension,
worsening renal insufficiency (should be used with caution, if at all,
in patients with renal artery stenosis), ACE-related cough | |
| ACE inhibitor (Lisinopril) | Reduces potentially deleterious LV remodeling | 5-40 mg qd (mortality benefit shown at 20-40 mg qd) | Reduction in mortality | Hypotension,
worsening renal insufficiency (should be used with caution, if at all,
in patients with renal artery stenosis), ACE-related cough | |
| ACE inhibitor (Enalapril) | Reduces potentially deleterious LV remodeling | 2.5-20 mg bid (mortality benefit achieved in clinical trials at 10 mg bid) | Reduction in mortality | Hypotension,
worsening renal insufficiency (should be used with caution, if at all,
in patients with renal artery stenosis), ACE-related cough | |
| ARB (Valsartan) | Antagonizes deleterious effects of angiotensin II | 20-160 mg bid (clinical benefit achieved in clinical trials at 160 mg bid) | Equivalent clinical outcomes compared to the ACE inhibitor captopril, with fewer side effects | Hypotension, worsening renal function, hyperkalemia | Beneficial when initiating 1-10 days after MI in patients with clinical heart failure and/or LV ejection fraction 35%-40% |
| Antilipemic agent, HMG-CoA reductase inhibitor (Lovastatin) | Similar
structure to the precursor of cholesterol (HMG-CoA); competitive
inhibitor of the enzyme that synthesizes cholesterol. Lowers LDL,
triglycerides, raises HDL | 10-80 mg qd | Reduction in morbidity and mortality in primary prevention | Most commonly liver enzyme abnormalities, myositis | |
| Antilipemic agent, HMG-CoA reductase inhibitor (Atorvastatin) | Similar
structure to the precursor of cholesterol (HMG-CoA); competitive
inhibitor of the enzyme that synthesizes cholesterol. Lowers LDL,
triglycerides, raises HDL. Also activates endothelial nitric oxide
synthase, decreases fibrinogen levels, and viscosity | 10-80 mg qd | Reduction in morbidity and mortality in secondary prevention | Most commonly liver enzyme abnormalities, myositis | Initiate
therapy as early as possible in the acute setting, certainly before
discharge. A single study showed a reduction in recurrent ischemia with
high dose atorvastatin (80 mg/d) therapy within 24-96 h of hospital
admission, however this was the only study of its kind and no dose
comparison was done; more data are needed (85) |
| Antilipemic agent, HMG-CoA reductase inhibitor (Pravastatin) | Similar
structure to the precursor of cholesterol (HMG-CoA); competitive
inhibitors of the enzyme that synthesizes cholesterol. Lowers LDL,
triglycerides, raises HDL. Also activates endothelial nitric oxide
synthase, decreases fibrinogen levels, and viscosity | 10-40 mg qd | Reduction in morbidity and mortality for both primary and secondary prevention | Liver enzyme abnormalities, rarely myositis | Initiate therapy as early as possible in the acute setting, certainly before discharge |
| Antilipemic agent, HMG-CoA reductase inhibitor (Simvastatin) | Similar
structure to the precursor of cholesterol (HMG-CoA); competitive
inhibitor of the enzyme that synthesizes cholesterol. Lowers LDL,
triglycerides, raises HDL. Also activates endothelial nitric oxide
synthase, decreases fibrinogen levels, and viscosity | 5-80 mg qd | Reduction in morbidity and mortality for both primary and secondary prevention | Liver enzyme abnormalities, rarely myositis | Initiate therapy as early as possible in the acute setting, certainly before discharge
|
| Aldosterone blocker (Eplerenone) | Selective aldosterone antagonist | 25 mg once daily beginning 3-14 days after acute MI, and increasing to 50 mg once daily after 4 weeks (if tolerated) | 15%
reduction in all-cause mortality, 17% reduction in cardiovascular
mortality, and 13% reduction in cardiovascular death or hospitalization
for cardiac events in patients with reduced left ventricular function
(ejection fraction 40% or less) and either clinical heart failure or
diabetes following acute MI | Hyperkalemia (5.5%
with eplerenone vs. 3.9% in control group), gastrointestinal disorders
(19.9% with eplerenone vs. 17.7% in control group) | Contraindicated
in patients with serum creatinine >2.5 mg/dL or serum potassium
>5.0 meq/L. Risk of hyperkalemia may be higher in older adults |
