Tips For Healthy

Acute myocardial infarction (AMI) and unstable angina are part of a spectrum known as the acute coronary syndromes (ACS), which have in common a ruptured athermanous plaque. These syndromes include unstable angina, non–Q-wave MI, and Q-wave MI. The ECG presentation of ACS includes ST-segment elevation infarction, ST-segment depression (including non–Quaver MI and unstable angi a), and no diagnostic Settlement and T-wave abnormalities. Patients with STsegment elevation will usually develop Q-wave MI. Patients with ischemic chest discomfort who do not have ST-segment elevation will develop Q-wave MI and non–Q-wave MI or unstable angina.

A. Patients with ischemic-type chest pain and STsegment elevation >1 mm in 2 contiguous leads have acute myocardial infarction. Reperfusion therapy with thrombolytics or angioplasty is recommended. B. Patients with ischemic-type pain but normal or nondiagnostic ECGs or ECGs consistent with ischemia (ST-segment depression only) usually do not have AMI. These patients should not be given fibrinolytic therapy.

C. Patients with normal or nondiagnostic ECGs usually do not have AMI, and they should be evaluated with serial cardiac enzymes and additional tests to determine the cause of their symptoms.

A. Patients with ST-segment elevation have AMI should receive reperfusion therapy with fibrinolytics or percutaneous coronary intervention.

1.Patients who present with ischemic pain and STsegment elevation (>1 mm in >2 contiguous leads) within 12 hours of onset of persistent pain should receive fibrinolytic therapy unless contraindicated. Patients with a new bundle branch block (obscuring ST-segment analysis) and history suggesting acute MI should also receive fibrinolytics or angioplasty.

a. ST Elevation (>1 mm in two or more contiguous leads), time to therapy 12 hours or less, age younger than 75 years.

b. A new bundle branch block (obscuring STsegment analysis) and history suggesting acute MI.

Activase) and Reteplase (Retavase) convert plasminogen to plasmin. Both agents are clot-specific and bind to new thrombus. Activase is superior to streptokinase. The alteplase thirty-day mortality rate of 6.3% is the lowest of the fibrinolytics, compared with 7.3% for streptokinase. Alteplase provides the earliest and most complete reperfusion.

3. Streptokinase (SK, Streptase) provides greater benefit in older patients with a smaller amount of myocardium at risk who present later and those with a greater risk of ICH. The dose of IV SK is 1.5 million units given over 60 minutes.

1. PCI is preferable to thrombolytic therapy if performed in a timely fashion by individuals skilled in the procedure. Coronary angioplasty provides higher rates of flow than thrombolytics and is associated with lower rates of reocclusion and postinfarction ischemia than fibrinolytic therapy.

2. Patients at high risk for mortality or severe LV dysfunction with signs of shock, pulmonary congestion, heart rate >100 bpm, and SBP <100 mm Hg should be sent to facilities capable of performing cardiac catheterization and rapid revascularization. When available within 90 minutes, PCI is recommended for all patients, particularly those who have a high risk of bleeding with fibrinolytic therapy. E. Heparin is recommended in patients receiving s e l e c t i v e f i b r i n o l y t i c a g e n t s (tPA/Reteplase/tenectaplase). A bolus dose of 60 U/kg should be followed by infusion at a rate of 12 U/kg/hour (a maximum bolus of 4000 U/kg and infusion of 1000 U/h for patients weighing <70 kg). An aPTT of 50 to 70 seconds is optimal.

F. Beta-blockade use during and after AMI reduces mortality by 36%. Contraindications to betablockers include severe LV failure and pulmonary edema, bradycardia (heart rate <60 bpm), hypotension (SBP <100 mm Hg), signs of poor peripheral perfusion, second- or third-degree heart block.

1. Metoprolol (Lopressor), 5 mg IV push every 5 minutes for three doses; followed by 25 mg PO bid. Titrate up to 100 mg PO bid OR

2. Atenolol (Tenormin), 5 mg IV, repeated in 5 minutes, followed by 50-100 mg PO qd. G. ACE-inhibitors increase survival in patients with AMI. ACE-inhibitors should be started between 6 to 24 hours after AMI and continued for 4-6 weeks, and indefinitely if ejection fraction <40%.

1. Captopril (Capoten) is given as a 6.25 mg initial dose and titrated up to 50 mg po bid, or

2. Lisinopril (Prinivil) may be given as 2.5-5 mg qd, titrate to 10-20 mg qd. VI. Management Non–Q-wave MI and high-risk unstable angina with ST-segment depression (Non-ST-Segment Elevation Syndromes)

1. Once unstable angina or non-ST-segment elevation MI has been identified, standard anti-ischemic treatments should be initiated.

2. Oxygen is indicated for patients with hypoxemia, cyanosis, or respiratory distress. Oxygen should be administered for at least the initial acute phase in all patients and longer in patients with congestive heart failure or a documented oxygen saturation of less than 92%. 3. Nitrates. Patients with ongoing chest pain should be given a 0.4-mg tablet of nitroglycerin (NitroQuick, Nitrostat) sublingually every 5 minutes for a total of three tablets in 15 minutes. If angina persists, continuous intravenous infusion of nitroglycerin starting at 10 micrograms/min should be instituted. Adjustments to 100 to 150 micrograms/min may be made as needed for pain if blood pressure permits. Tolerance to continuous nitroglycerin administration can develop after 24 hours.

4. Morphine. Intravenous morphine sulfate may be administered when ischemic chest pain is not relieved with nitroglycerin or when acute pulmonary congestion or severe agitation is noted.

a. Beta-blockade remains an important mainstay of therapy for unstable angina and non-ST-segment elevation MI. It helps reduce cardiac workload and myocardial oxygen demand as well as improve blood flow in coronary arteries. Unless contraindicated, beta-blockers should always be given to patients presenting with an unstable coronary syndrome.

b. Intravenous therapy should be administered even when patients are already taking oral beta-blockers. Options include metoprolol (Lopressor), 5 mg given intravenously every 5 minutes for a total of 15 mg, and propranolol (Inderal), 1 mg given intravenously every 5 minutes for up to 5 mg. Esmolol (Brevibloc) infusion starting at 50 micrograms/kg per minute for a maximum dose of 200 to 300 micrograms/ kg per minute can also be used. The target heart rate with beta-blockade is less than 60 beats per minute.

6. Angiotensin-converting enzyme (ACE) inhibitors should be given early on in patients with left ventricular dysfunction or evidence of congestive heart failure. 7. Intra-aortic balloon pump may be considered in patients with severe ischemia refractory to intensive medical therapy or in hemodynamically unstable patients before or after coronary angiography.

B. Anticoagulant therapy

a. The low-molecular-weight heparins have a longer half-life than unfractionated heparin and thus allow subcutaneous injections to be given once or twice daily. In addition, these agents do not require serial monitoring or frequent dose adjustments. Heparin-induced thrombocytopenia is less common with low-molecular-weight heparins than with unfractionated heparin.

b. Enoxaparin (Lovenox) use in patients with non-ST-segment elevation acute coronary syndromes significantly reduces the risk of point of death, MI, recurrent angina, and need for urgent revascularization compared to unfractionated heparin. Enoxaparin (Lovenox) should be considered as a replacement for unfractionated heparin in non-ST-segment elevation acute coronary syndromes. Enoxaparin (Lovenox) 1.0 mg/kg SQ q12h

2. Statin therapy. Use of 3-hydroxy- 3-methylglutaryl coenzyme A reductase inhibitors (“statins”) as part of an early, aggressive lipid-lowering approach results in improved endothelial function, vasodilation, decreased platelet aggregation, and plaque stabilization.

1. Antiplatelet drug therapy is a crucial component of management of acute coronary syndromes. The risk of death or nonfatal MI can be reduced with early antiplatelet therapy in patients with unstable angina or non-ST-segment elevation MI.

a. Aspirin exerts its antiplatelet effect by irreversibly inhibiting the platelet enzyme cyclooxygenase-1; this inhibition prevents formation of thromboxane A2, a potent vasoconstrictor and activator of platelet aggregation. Aspirin decreases rates of mortality and cardiac events. In addition, aspirin in combination with heparin further reduces the risk of these adverse outcomes.

b. Aspirin should be administered as soon as possible after presentation of an acute coronary syndrome and continued indefinitely. Patients not previously given aspirin should chew the initial dose to rapidly achieve high blood levels. Aspirin therapy should be continued at a daily dose of 325 mg.

3. Clopidogrel (Plavix) is a thienopyridine derivative that exerts an antiplatelet effect by blocking adenosine diphosphate-dependent platelet activation. Clopidogrel should be added to aspirin therapy as part of the antiplatelet regimen in acute coronary syndromes at a daily dose of 75 mg for nine to 12 months.

a. The GpIIb-IIIa receptor on the platelet surface serves as the final common pathway for platelet-platelet interaction and thrombus formation. Three GpIIb-IIIa inhibitor drugs are commercially available: abciximab (ReoPro), eptifibatide (Integrilin), and tirofiban (Aggrastat). The various GpIIb-IIIa receptor antagonists have been approved for treatment of medically refractory unstable angina. However, abciximab is not currently approved without planned percutaneous coronary intervention or cardiac catheterization.

b. Bleeding remains the most frequent complication of GpIIb-IIIa inhibitors. Severe thrombocytopenia (platelets, <50 X 103/microliters) occurs in 0.1% to 0.7% of cases. Contraindicat ions include cerebrovascular accident or neurosurgical intervention within less than 6 months, surgery or gastrointestinal hemorrhage within less than 6 weeks, intracranial malignancy, and platelet count less than 100 X 103/microliters. Eptifibatide and tirofiban require dose adjustments with a serum creatinine level of more than 2 mg/dL. c. Because of the significant risk of bleeding with use of GpIIb-IIIa antagonists (which are given in conjunction with other antiplatelet and anticoagulation treatment), routine surveillance for mucocutaneous bleeding, bleeding at the vascular access site, and spontaneous bleeding is important. Hemoglobin level and platelet counts should be measured daily.

d. GpIIb-IIIa antagonist therapy should be strongly considered for patients who have high-risk features, such as elevated levels of cardiac markers, dynamic ST-segmentchanges, and refractory chest pain and in whom early angiography and percutaneous coronary intervention are planned.

(1) Abciximab (ReoPro), 0.25 mg/kg IVP over 2 min, then 0.125 mcg/kg/min (max 10 mcg/min) for 12 hours.

(2) Eptifibatide (Integrilin), 180 mcg/kg IVP over 2 min, then 2 mcg/kg/min for 24-72 hours. Use 0.5 mcg/kg/min if creatinine is >2.0 mg/dL.

(3) Tirofiban (Aggrastat), 0.4 mcg/kg/min for 30 min, then 0.1 mcg/kg/min IV infusion for 24-72 hours. Reduce dosage by 50% if the creatine clearance is <30 mL/min.

A. Early invasive approach. An early invasive approach was most beneficial in patients with intermediate- or high-risk factors. Such factors include an elevated troponin level, ST-segment changes, age greater than 65 years, diabetes, and an elevated TIMI risk score. In low-risk patients, a routine early invasive approach provided no benefit and tended to increase the adverse event rate.