Cardiovascular Disorders. Acute Coronary Syndromes

Acute coronary syndromes (ACSs) include all syndromes compatible with acute myocardial ischemia resulting from imbalance between myocardial oxygen demand and supply.

• ACSs are classified according to electrocardiographic (ECG) changes into 

(1) ST-segment-elevation (STE) myocardial infarction (MI) or

(2) non–ST-segmentelevation (NSTE) ACS, which includes NSTE MI and unstable angina (UA).

PATHOPHYSIOLOGY 

• Endothelial dysfunction, inflammation, and formation of fatty streaks contribute to development of atherosclerotic coronary artery plaques. 

• The cause of ACS in more than 90% of patients is rupture, fissuring, or erosion of an unstable atheromatous plaque. A clot forms on top of the ruptured plaque. Exposure of collagen and tissue factor induces platelet adhesion and activation, which promote release of adenosine diphosphate (ADP) and thromboxane A2 from platelets producing vasoconstriction and platelet activation. A change in the conformation of the glycoprotein (GP) IIb/IIIa surface receptors of platelets occurs that cross-links platelets to each other through fibrinogen bridges. 

• Simultaneously, activation of the extrinsic coagulation cascade occurs as a result of exposure of blood to the thrombogenic lipid core and endothelium, which are rich in tissue factor. This leads to formation of a fibrin clot composed of fibrin strands, cross-linked platelets, and trapped red blood cells. 

• Ventricular remodeling occurs after MI and is characterized by left ventricular dilation and reduced pumping function, leading to cardiac failure. 

• Complications of MI include cardiogenic shock, heart failure (HF), valvular dysfunction, arrhythmias, pericarditis, stroke secondary to left ventricular (LV) thrombus embolization, venous thromboembolism, and LV free-wall rupture.

CLINICAL PRESENTATION 

• Predominant symptom is midline anterior chest discomfort (usually at rest), severe new-onset angina, or increasing angina that lasts at least 20 minutes. Discomfort may radiate to the shoulder, down the left arm, to the back, or to the jaw. Accompanying symptoms may include nausea, vomiting, diaphoresis, and shortness of breath. 

• No specific features indicate ACS on physical examination. However, patients with ACS may present with signs of acute HF or arrhythmias.

DIAGNOSIS 

• Obtain 12-lead ECG within 10 minutes of presentation. Key findings indicating myocardial ischemia or MI are STE, ST-segment depression, and T-wave inversion. Appearance of a new left bundle-branch block with chest discomfort is highly specific for acute MI. Some patients with myocardial ischemia have no ECG changes, so biochemical markers and other risk factors for coronary artery disease (CAD) should be assessed. 

• Biochemical markers of myocardial cell death are important for confirming diagnosis of acute MI. Diagnosis is confirmed with detection of rise and/or fall of cardiac Acute Coronary Syndromes Ch a p t e r 5 38 SECTION 2 | Cardiovascular Disorders biomarkers (cardiac troponin preferred) with at least one value above the 99th percentile of the upper reference limit and at least one of the following: (1) symptoms of ischemia; (2) new significant ST-segment–T-wave changes or new left bundlebranch block; (3) pathological Q waves; or (4) imaging evidence of new loss of viable myocardium or new regional wall motion abnormality. Typically, a blood sample is obtained once in the emergency department, then 6 to 9 hours later. 

• Patient symptoms, past medical history, ECG, and biomarkers are used to stratify patients into low, medium, or high risk of death, MI, or likelihood of failing pharmacotherapy and needing urgent coronary angiography and percutaneous coronary intervention (PCI)

TREATMENT 

• Goals of Treatment: Short-term goals include: (1) early restoration of blood flow to the infarct-related artery to prevent infarct expansion (in the case of MI) or prevent complete occlusion and MI (in UA), (2) prevention of death and other complications, (3) prevention of coronary artery reocclusion, (4) relief of ischemic chest discomfort, and (5) resolution of ST-segment and T-wave changes on ECG. Long-term goals include control of cardiovascular (CV) risk factors, prevention of additional CV events, and improvement in quality of life.

GENERAL APPROACH 

• General measures include hospital admission, oxygen if saturation is low, continuous multilead ST-segment monitoring for arrhythmias and ischemia, frequent measurement of vital signs, bedrest for 12 hours in hemodynamically stable patients, use of stool softeners to avoid Valsalva maneuver, and pain relief. 

• Obtain serum potassium, magnesium, glucose, and creatinine; baseline complete blood cell count (CBC) and coagulation tests; and fasting lipid panel. Draw lipid panel within the first 24 hours of hospitalization because values for cholesterol (an acute phase reactant) may be falsely low after that period. 

• It is important to triage and treat patients according to their risk category (Fig. 5–1). 

• Patients with STE MI are at high risk of death, so initiate immediate efforts to reestablish coronary perfusion and adjunctive pharmacotherapy

NONPHARMACOLOGIC THERAPY 

• For patients with STE MI presenting within 12 hours of symptom onset, the reperfusion treatment of choice is early reperfusion with primary PCI of the infarct artery within 90 minutes of first medical contact. 

• For patients with NSTE ACS, practice guidelines recommend coronary angiography with either PCI or coronary artery bypass graft (CABG) surgery revascularization as early treatment for high-risk patients; such an approach may also be considered for patients not at high risk.

EARLY PHARMACOTHERAPY FOR STE MI (Fig. 5–2) 

• In addition to reperfusion therapy, American College of Cardiology Foundation/ American Heart Association (ACCF/AHA) guidelines recommend that all patients with STE MI and without contraindications should receive within the first day of hospitalization and preferably in the emergency department: 

(1) intranasal oxygen (if oxygen saturation is low), 

(2) sublingual (SL) nitroglycerin (NTG), 

(3) aspirin, 

(4) a P2Y12 platelet inhibitor, 

(5) and anticoagulation with bivalirudin, unfractionated heparin (UFH), or enoxaparin. 

• Administer a GP IIb/IIIa inhibitor with UFH to patients undergoing primary PCI. 

Give IV β-blockers and IV NTG to select patients. 

Initiate oral β-blockers the first day in patients without cardiogenic shock. 

Administer morphine to patients with refractory angina as an analgesic and venodilator that lowers preload. 

Start an angiotensinconverting enzyme (ACE) inhibitor within 24 hours in patients who have either anterior wall MI or LVEF of 40% or less and no contraindications.

Fibrinolytic Therapy 

• A fibrinolytic agent is indicated in patients with STE MI presenting within 12 hours of the onset of chest discomfort who have at least 1 mm of STE in two or more contiguous ECG leads and are unable to undergo primary PCI within 120 minutes of medical contact. Limit use of fibrinolytics between 12 and 24 hours after symptom onset to patients with ongoing ischemia. 

• It is not necessary to obtain the results of biochemical markers before initiating fibrinolytic therapy. • Absolute contraindications to fibrinolytic therapy include: 

(1) history of hemorrhagic stroke (at any time), 

(2) ischemic stroke within 3 months, 

(3) active internal bleeding, 

(4) known intracranial neoplasm, 

(5) known structural cerebrovascular lesion, 

(6)suspected aortic dissection, and 

(7) significant closed head or facial trauma within 3 months. Primary PCI is preferred in these situations. 

• A fibrin-specific agent (alteplase, reteplase, or tenecteplase) is preferred over the non–fibrin-specific agent streptokinase. 

• Treat eligible patients as soon as possible, but preferably within 30 minutes from the time they present to the emergency department, with one of the following regimens: 

✓ Alteplase: 15 mg IV bolus followed by 0.75 mg/kg infusion (maximum 50 mg) over 30 minutes, followed by 0.5 mg/kg infusion (maximum 35 mg) over 60 minutes (maximum dose 100 mg) 

✓ Reteplase: 10 units IV over 2 minutes, followed 30 minutes later with another 10 units IV over 2 minutes 

✓ Tenecteplase: A single IV bolus dose given over 5 seconds based on patient weight: 30 mg if less than 60 kg; 35 mg if 60 to 69.9 kg; 40 mg if 70 to 79.9 kg; 45 mg if 80 to 89.9 kg; and 50 mg if 90 kg or greater 

✓ Streptokinase: 1.5 million units in 50 mL of normal saline or 5% dextrose in water IV over 60 minutes 

• Intracranial hemorrhage (ICH) and major bleeding are the most serious side effects. The risk of ICH is higher with fibrin-specific agents than with streptokinase. 

However, the risk of systemic bleeding other than ICH is higher with streptokinase than with fibrin-specific agents.

Aspirin 

• Administer aspirin to all patients without contraindications within 24 hours before or after hospital arrival. It provides additional mortality benefit in patients with STE ACS when given with fibrinolytic therapy. 

• In patients experiencing an ACS, non–enteric-coated aspirin, 160 to 325 mg, should be chewed and swallowed as soon as possible after the onset of symptoms or immediately after presentation to the emergency department regardless of the reperfusion strategy being considered. Patients undergoing PCI not previously taking aspirin should receive 325 mg non–enteric-coated aspirin. 

• A daily maintenance dose of 75 to 162 mg is recommended thereafter and should be continued indefinitely. Because of increased bleeding risk in patients receiving aspirin plus a P2Y12 inhibitor, low-dose aspirin (81 mg daily) is preferred following PCI. 

• Discontinue other nonsteroidal anti-inflammatory drugs(NSAIDs) and cyclooxygenase-2 (COX-2) selective inhibitors at the time of STE MI due to increased risk of death, reinfarction, HF, and myocardial rupture. 

• The most frequent side effects of aspirin include dyspepsia and nausea. Inform patients about the risk of GI bleeding

Platelet P2Y12 Inhibitors 

• Clopidogrel, prasugrel, and ticagrelor block a subtype of ADP receptor (the P2Y12 receptor) on platelets, preventing binding of ADP to the receptor and subsequent expression of platelet GP IIb/IIIa receptors, reducing platelet aggregation. 

• A P2Y12 receptor inhibitor in addition to aspirin is recommended for all patients with STE MI. For patients undergoing primary PCI, give clopidogrel, prasugrel, or ticagrelor, in addition to aspirin, to prevent subacute stent thrombosis and longerterm CV events. 

• The recommended duration of P2Y12 inhibitors for a patient undergoing PCI (either STE MI or NSTE ACS) is at least 12 months for patients receiving either a bare metal or drug-eluting stent. 

• If CABG surgery is planned, withhold clopidogrel and ticagrelor for 5 days, and prasugrel at least 7 days, to reduce risk of postoperative bleeding, unless the need for revascularization outweighs the bleeding risk. 

• Clopidogrel: 

300 mg oral loading dose followed by 75 mg orally daily in patients receiving a fibrinolytic or who do not receive reperfusion therapy. Avoid loading dose in patients aged 75 years or more. A 600-mg oral loading dose is recommended before primary PCI, except that 300 mg should be given if within 24 hours of fibrinolytic therapy.

 Prasugrel: 

60 mg oral loading dose followed by 10 mg orally once daily for patients weighing 60 kg (132 lb) or more. 

• Ticagrelor: 180 mg oral loading dose in patients undergoing PCI, followed by 90 mg orally twice daily. 

• The most frequent side effects of clopidogrel and prasugrel include nausea, vomiting, and diarrhea, (2%–5% of patients). Thrombotic thrombocytopenic purpura (TTP) has been reported rarely with clopidogrel. Ticagrelor is associated with nausea (4%), diarrhea (3%), dyspnea (14%), and, rarely, ventricular pauses and bradyarrhythmias. 

• In patients with STE MI receiving fibrinolysis, early therapy with clopidogrel 75 mg once daily during hospitalization and up to 28 days reduces mortality and reinfarction without increasing risk of major bleeding. In adults younger than 75 years receiving fibrinolytics, the first dose of clopidogrel can be a 300-mg loading dose. 

• For patients with STE MI who do not undergo reperfusion therapy with either primary PCI or fibrinolysis, clopidogrel is the preferred P2Y12 inhibitor added to aspirin and should be continued for at least 14 days (and up to 1 year). Ticagrelor may also be an option in medically managed patients with ACS.

Glycoprotein IIb/IIIa Receptor Inhibitors

• GP IIb/IIIa receptor inhibitors block the final common pathway of platelet aggregation, namely cross-linking of platelets by fibrinogen bridges between the GP IIb and IIIa receptors on the platelet surface. 

• Abciximab (IV or intracoronary administration), eptifibatide, or tirofiban may be administered in patients with STE MI undergoing primary PCI who are treated with UFH. Do not administer GP IIb/IIIa inhibitors to patients with STE MI who will not be undergoing PCI. 

• Abciximab: 0.25 mg/kg IV bolus given 10 to 60 minutes before the start of PCI, followed by 0.125 mcg/kg/min (maximum 10 mcg/min) for 12 hours. 

• Eptifibatide: 180 mcg/kg IV bolus, repeated in 10 minutes, followed by infusion of 2 mcg/kg/min for 18 to 24 hours after PCI. 

• Tirofiban: 25 mcg/kg IV bolus, then 0.15 mcg/kg/min up to 18 to 24 hours after PCI. 

• Routine use of a GP IIb/IIIa receptor inhibitor is not recommended in patients who have received fibrinolytics or in those receiving bivalirudin because of increased bleeding risk. 

• Bleeding is the most significant adverse effect. Do not use GP IIb/IIIa inhibitors in patients with a history of hemorrhagic stroke or recent ischemic stroke. Risk of bleeding is increased in patients with chronic kidney disease; reduce the dose of eptifibatide and tirofiban in renal impairment. An immune-mediated thrombocytopenia occurs in approximately 5% of patients with abciximab and fewer than 1% of patients receiving eptifibatide or tirofiban.

Anticoagulants 

• Either UFH or bivalirudin is preferred for patients undergoing primary PCI, whereas for fibrinolysis, either UFH, enoxaparin, or fondaparinux may be used. 

• UFH initial dose for primary PCI is 50 to 70 units/kg IV bolus if a GP IIb/IIIa inhibitor is planned and 70 to 100 U/kg IV bolus if no GP IIb/IIIa inhibitor is planned; give supplemental IV bolus doses to maintain the target activated clotting time (ACT). 

• UFH initial dose with fibrinolytics is 60 U/kg IV bolus (maximum 4000 units), followed by constant IV infusion of 12 U/kg/h (maximum 1000 U/h). Adjust the UFH infusion dose frequently to maintain a target activated partial thromboplastin time (aPTT) of 1.5 to 2 times control (50–70 seconds). Measure the first aPTT at 3 hours in patients with STE ACS who are treated with fibrinolytics and at 4 to 6 hours in patients not receiving thrombolytics or undergoing primary PCI. 

• Enoxaparin dose is 1 mg/kg subcutaneous (SC) every 12 hours (creatinine clearance [Clcr] ≥30 mL/min) or 24 hours if impaired renal function (Clcr 15–29 mL/min). For patients with STE MI receiving fibrinolytics, enoxaparin 30 mg IV bolus is followed immediately by 1 mg/kg SC every 12 hours if younger than 75 years. In patients 75 years and older, give enoxaparin 0.75 mg/kg SC every 12 hours. Continue enoxaparin throughout hospitalization or up to 8 days. 

• Bivalirudin dose for PCI in STE MI is 0.75 mg/kg IV bolus, followed by 1.75 mg/ kg/h infusion. Discontinue at the end of PCI or continue at 0.25 mg/kg/h if prolonged anticoagulation is necessary. 

• Fondaparinux dose is 2.5 mg IV bolus followed by 2.5 mg SC once daily starting on hospital day 2. • For patients undergoing PCI, discontinue anticoagulation immediately after the procedure. In patients receiving an anticoagulant plus a fibrinolytic, continue UFH for a minimum of 48 hours and enoxaparin and fondaparinux for the duration of hospitalization, up to 8 days. In patients who do not undergo reperfusion therapy, anticoagulant therapy may be administered for up to 48 hours for UFH or for the duration of hospitalization for enoxaparin or fondaparinux.

β-Adrenergic Blockers 

• If no contraindications, administer a β-blocker early (within the first 24 hours) and continue indefinitely. 

• Benefits result from blockade of β1 receptors in the myocardium, which reduces heart rate, myocardial contractility, and BP, thereby decreasing myocardial oxygen demand. Reduced heart rate increases diastolic time, thus improving ventricular filling and coronary artery perfusion. 

• β-Blockers reduce risk for recurrent ischemia, infarct size, reinfarction, and ventricular arrhythmias. • Usual doses of β-blockers, with target resting heart rate of 50 to 60 beats/min: ✓ Metoprolol: 5 mg by slow (over 1–2 minutes) IV bolus, repeated every 5 minutes for total initial dose of 15 mg. If a conservative regimen is desired, reduce initial doses to 1 to 2 mg. Follow in 1 to 2 hours by 25 to 50 mg orally every 6 hours. If appropriate, initial IV therapy may be omitted. ✓ Propranolol: 0.5 to 1 mg slow IV push, followed in 1 to 2 hours by 40 to 80 mg orally every 6 to 8 hours. If appropriate, the initial IV therapy may be omitted. ✓ Atenolol: 5 mg IV dose, followed 5 minutes later by a second 5 mg IV dose, then 50 to 100 mg orally once daily beginning 1 to 2 hours after the IV dose. The initial IV therapy may be omitted. 

• The most serious side effects early in ACS include hypotension, acute HF, bradycardia, and heart block. Initial acute administration of β-blockers is not appropriate for patients presenting with acute HF but may be attempted in most patients before discharge after treatment of acute HF. 

• Continue β-blockers for at least 3 years in patients with normal LV function and indefinitely in patients with LV systolic dysfunction and LVEF of 40% or less.

Statins 

• Administer a high-intensity statin, either atorvastatin 80 mg or rosuvastatin 40 mg, to all patients prior to PCI (regardless of prior lipid-lowering therapy) to reduce the frequency of periprocedural MI following PCI.

Nitrates 

• NTG causes venodilation, which lowers preload and myocardial oxygen demand. In addition, arterial vasodilation may lower BP, thereby reducing myocardial oxygen demand. Arterial dilation also relieves coronary artery vasospasm and improves myocardial blood flow and oxygenation. 

• Immediately upon presentation, administer one SL NTG tablet (0.4 mg) every 5 minutes for up to three doses to relieve chest pain and myocardial ischemia. 

• Intravenous NTG is indicated for patients with an ACS who do not have a contraindication and who have persistent ischemia, HF, or uncontrolled high BP. The usual dose is 5 to 10 mcg/min by continuous infusion, titrated up to 100 mcg/min until relief of symptoms or limiting side effects (eg, headache or hypotension). Continue treatment for approximately 24 hours after ischemia is relieved.

• Oral nitrates play a limited role in ACS because clinical trials have failed to show a mortality benefit for IV followed by oral nitrate therapy in acute MI. 

• The most significant adverse effects of nitrates include tachycardia, flushing, headache, and hypotension. Nitrates are contraindicated in patients who have taken the oral phosphodiesterase-5 inhibitors sildenafil or vardenafil within the prior 24 hours or tadalafil within the prior 48 hours.

Calcium Channel Blockers 

• After STE MI, calcium channel blockers (CCBs) are used for relief of ischemic symptoms in patients who have contraindications to β-blockers. There is little clinical benefit beyond symptom relief, so avoid CCBs in acute management of all ACSs unless there is a clear symptomatic need or contraindication to β-blockers. 

• A CCB that lowers heart rate (diltiazem or verapamil) is preferred unless the patient has LV systolic dysfunction, bradycardia, or heart block. In those cases, either amlodipine or felodipine is preferred. Avoid nifedipine because it causes reflex sympathetic activation, tachycardia, and worsened myocardial ischemia. 

✓ Diltiazem: 120 to 360 mg sustained release orally once daily 

✓ Verapamil: 180 to 480 mg sustained release orally once daily 

✓ Amlodipine: 5 to 10 mg orally once daily

EARLY PHARMACOTHERAPY FOR NSTE ACS (Fig. 5–3) 

• Early pharmacotherapy for NSTE ACS is similar to that for STE ACS. 

• In absence of contraindications, treat all patients in the emergency department with intranasal oxygen (if oxygen saturation is low), SL NTG, aspirin, and an anticoagulant (UFH, enoxaparin, fondaparinux, or bivalirudin). 

• High-risk patients should proceed to early angiography and may receive a GP IIb/ IIIa inhibitor (optional with either UFH or enoxaparin but should be avoided with bivalirudin). 

• Administer a P2Y12 inhibitor to all patients. 

• Give IV β-blockers and IV NTG to select patients. 

• Initiate oral β-blockers within the first 24 hours in patients without cardiogenic shock. 

• Give morphine to patients with refractory angina, as described previously. 

• Fibrinolytic therapy is never administered in NSTE ACS.

Aspirin 

• Aspirin reduces risk of death or MI by approximately 50% compared with no antiplatelet therapy in patients with NSTE ACS. Dosing of aspirin is the same as for STE ACS, and aspirin is continued indefinitely

Anticoagulants 

• For patients treated by an early invasive approach with early coronary angiography and PCI, administer UFH, enoxaparin, or bivalirudin. 

• If an initial conservative strategy is planned (no coronary angiography or revascularization), enoxaparin, UFH, or low-dose fondaparinux is recommended. 

• Continue therapy for at least 48 hours for UFH, until the patient is discharged from the hospital (or 8 days, whichever is shorter) for either enoxaparin or fondaparinux, and until the end of the PCI or angiography procedure (or up to 72 hours after PCI) for bivalirudin. 

• For NSTE ACS, the dose of UFH is 60 U/kg IV bolus (maximum 4000 units), followed by a continuous IV infusion of 12 U/kg/h (maximum 1000 U/h). Titrate the dose to maintain aPTT between 1.5 and 2 times control

P2Y12 Inhibitors 

• When an initial invasive strategy is selected, there are two initial options for dual antiplatelet therapy depending on choice of P2Y12 inhibitor: 

1. Aspirin plus early use of clopidogrel or ticagrelor (in the emergency department) 

2. Aspirin plus double-bolus dose eptifibatide plus an eptifibatide infusion or highdose tirofiban bolus plus infusion administered at the time of PCI.

• For subsequent antiplatelet therapy in patients undergoing PCI initially treated with regimen 1 above, a GP IIb/IIIa inhibitor (abciximab, eptifibatide, or high-dose tirofiban) can be added, and then clopidogrel continued with low-dose ASA. 

• For patients undergoing PCI initially treated with option 2, clopidogrel, prasugrel, or ticagrelor can be started within 1 hour after PCI and the P2Y12 inhibitor continued with low-dose aspirin. Following PCI, continue dual oral antiplatelet therapy for at least 12 months. 

• For patients receiving an initial conservative strategy, either clopidogrel or ticagrelor can be administered in addition to aspirin. Continue dual antiplatelet therapy for at least 12 months.

Glycoprotein IIb/IIIa Receptor Inhibitors 

• The role of GP IIb/IIIa inhibitors in NSTE ACS is diminishing as P2Y12 inhibitors are used earlier, and bivalirudin is often selected as the anticoagulant. 

• Routine administration of eptifibatide (added to aspirin and clopidogrel) prior to angiography and PCI in NSTE ACS does not reduce ischemic events and increases bleeding risk. Therefore, the two antiplatelet initial therapy options described in the previous section are preferred.

• For low-risk patients and a conservative management strategy, there is no role for routine GP IIb/IIIa inhibitors because bleeding risk exceeds the benefit.

Nitrates 

• Administer SL NTG followed by IV NTG to patients with NSTE ACS and ongoing ischemia, HF, or uncontrolled high BP. Continue IV NTG for approximately 24 hours after ischemia relief. 

β-Blockers 

• In the absence of contraindications, administer oral β-blockers to all patients with NSTE ACS within 24 hours of hospital admission. Benefits are assumed to be similar to those seen in patients with STE MI. 

• Continue β-blockers indefinitely in patients with LVEF of 40% or less and for at least 3 years in patients with normal LV function. 

Calcium Channel Blockers 

• As described previously for STE ACS, CCBs should not be administered to most patients with ACS

SECONDARY PREVENTION FOLLOWING MI 

• Goals of Treatment: 

The long-term goals after MI are to:
(1) control modifiable coronary heart disease (CHD) risk factors;
(2) prevent development of systolic HF;
(3) prevent recurrent MI and stroke;
(4) prevent death, including sudden cardiac death; and
(5) prevent stent thrombosis after PCI.

PHARMACOTHERAPY 

• Start pharmacotherapy that has been proven to decrease mortality, HF, reinfarction or stroke, and stent thrombosis prior to hospital discharge for secondary prevention. 

• After MI from either STE MI or NSTE ACS, all patients (in the absence of contraindications) should receive indefinite treatment with aspirin (or clopidogrel if aspirin contraindications), an ACE inhibitor, and a “high-intensity” statin for secondary prevention of death, stroke, or recurrent infarction. 

• Start ACE inhibitors and continue indefinitely in all patients after MI to reduce mortality, decrease reinfarction, and prevent HF. Most patients with CAD (not just those with ACS or HF) benefit from an ACE inhibitor. The dose should be low initially and titrated to the dose used in clinical trials if tolerated, for example: 

✓ Captopril: 6.25 to 12.5 mg initially; target dose 50 mg two or three times daily 

✓ Enalapril: 2.5 to 5 mg initially; target dose 10 mg twice daily

✓ Lisinopril: 2.5 to 5 mg initially; target dose 10 to 20 mg once daily 

✓ Ramipril: 1.25 to 2.5 mg initially; target dose 5 mg twice daily or 10 mg once daily 

✓ Trandolapril: 1 mg initially; target dose 4 mg once daily 

• An angiotensin receptor blocker may be prescribed for patients with ACE inhibitor cough and a low LVEF and HF after MI: 

✓ Candesartan: 4 to 8 mg initially; target dose 32 mg once daily 

✓ Valsartan: 40 mg initially; target dose 160 mg twice daily 

• Continue a β-blocker for at least 3 years in patients without HF or an ejection fraction of 40% or less and indefinitely in patients with LV systolic dysfunction or HF symptoms. A CCB can be used to prevent anginal symptoms in patients who cannot tolerate or have contraindications to β-blockers but should not be used routinely in the absence of such findings. 

• Continue a P2Y12 inhibitor for at least 12 months for patients undergoing PCI and for patients with NSTE ACS receiving a medical management strategy. Continue clopidogrel for at least 14 days in patients with STE MI not undergoing PCI. 

• To reduce mortality, consider a mineralocorticoid receptor antagonist (eplerenone or spironolactone) within the first 7 days after MI in all patients already receiving an ACE inhibitor (or ARB) and a β-blocker and have an LVEF of 40% or less and either HF symptoms or diabetes mellitus. The drugs are continued indefinitely. 

✓ Eplerenone: 25 mg initially; target dose 50 mg once daily 

✓ Spironolactone: 12.5 mg initially; target dose 25 to 50 mg once daily 

• All patients with CAD should receive dietary counseling and a statin to reach appropriate targets based on current practice guidelines. 

• Prescribe a short-acting SL NTG or lingual NTG spray for all patients to relieve anginal symptoms when necessary. Chronic long-acting nitrates have not been shown to reduce CHD events after MI and are not used in ACS patients who have undergone revascularization unless the patient has chronic stable angina or significant coronary stenosis that was not revascularized. 

• For all ACS patients, treat and control modifiable risk factors such as hypertension (HTN), dyslipidemia, obesity, smoking, and DM.

EVALUATION OF THERAPEUTIC OUTCOMES 

• Monitoring parameters for efficacy for both STE and NSTE ACS include: 

(1) relief of ischemic discomfort, 

(2) return of ECG changes to baseline, and 

(3) absence or resolution of HF signs and symptoms. 

• Monitoring parameters for adverse effects are dependent on the individual drugs used. In general, the most common adverse reactions from ACS therapies include hypotension and bleeding.