Acute Coronary Syndromes Lecture 1 PDF

Applied Therapeutics fifth stage Lecture:1 Acute Coronary Syndromes INTRODUCTION Acute coronary syndrome (ACS) includes all syndromes compatible with acute myocardial ischemia...

Applied Therapeutics fifth stage Lecture:1 Acute Coronary Syndromes INTRODUCTION Acute coronary syndrome (ACS) includes all syndromes compatible with acute myocardial ischemia resulting from imbalance between myocardial oxygen demand and supply. ACS is classified according to electrocardiographic (ECG) changes into: (1) ST- segment-elevation myocardial infarction (STEMI) or (2) non–ST-segment-elevation ACS (NSTE-ACS), which includes non–ST-segment-elevation MI (NSTEMI) and unstable angina (UA). PATHOPHYSIOLOGY Endothelial dysfunction, inflammation, and formation of fatty streaks contribute to development of atherosclerotic coronary artery plaques. With rupture of an atherosclerotic plaque, exposure of collagen and tissue factor induces platelet adhesion and activation, promoting release of adenosine diphosphate (ADP) and thromboxane A2 from platelets, leading to vasoconstriction and platelet activation. A change in the conformation of the glycoprotein 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 after MI is characterized by left ventricular (LV) dilation and reduced pumping function, leading to heart failure (HF). Complications of MI include cardiogenic shock, HF, valvular dysfunction, arrhythmias, pericarditis, stroke secondary to LV thrombus embolization, venous thromboembolism, LV free-wall or septal rupture, aneurysm formation, and ventricular and atrial tachyarrhythmias. CLINICAL PRESENTATION The predominant symptom is midline anterior chest pain (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. 1  No specific features indicate ACS on physical examination. However, patients with ACS may present with signs of acute decompensated 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. Some patients with myocardial ischemia have no ECG changes, so biochemical markers and other risk factors for coronary artery disease (CAD) should be assessed. Diagnosis of MI is confirmed with detection of rise and/or fall of cardiac biomarkers (mainly troponin T or I) with ECG changes. Typically, a blood sample is obtained once in the emergency department, then 3 to 6 hours after symptom onset. 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 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. NONPHARMACOLOGIC THERAPY For patients with STEMI presenting within 12 hours of symptom onset, early reperfusion with primary PCI of the infarct artery within 90 minutes of first medical contact is the reperfusion treatment of choice. For patients with NSTE-ACS, practice guidelines recommend an early (within 24 hours) coronary angiography, and revascularization with either PCI or CABG surgery as early treatment for high-risk patients; such an approach may also be considered for patients not at high risk. EARLY PHARMACOTHERAPY FOR STEMI In addition to reperfusion therapy, all patients with STEMI 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, and (5) 2  anticoagulation with bivalirudin, unfractionated heparin (UFH), enoxaparin, or fondaparinux (depending on reperfusion strategy) A glycoprotein IIb/IIIa receptor inhibitor (GPI) may be administered with UFH to patients undergoing primary PCI. Intravenous NTG may be given to select patients. β-Blockers are reasonable at the time of presentation for patients with hypertension and ongoing ischemia but without cardiogenic shock or other contraindications. Morphine may be given for refractory angina as an analgesic and venodilator to lower preload, but its use should be limited. An angiotensin-converting enzyme (ACE) inhibitor is recommended within 24 hours in patients who have either anterior wall MI or LV ejection fraction (LVEF) of 40% or less and no contraindications. Fibrinolytic Therapy A fibrinolytic agent is indicated in patients with STEMI who present within 12 hours of the onset of chest discomfort to a hospital not capable of primary PCI and have at least a 1-mm STE in two or more contiguous ECG leads, have no absolute contraindications to fibrinolytic therapy and cannot be transferred and undergo primary PCI within 120 minutes of medical contact. Fibrinolytic use between 12 and 24 hours after symptom onset should be limited to patients with ongoing ischemia. It is not necessary to obtain the troponin result before initiating fibrinolytic therapy. Contraindications to fibrinolytic therapy include: any prior intracranial hemorrhage, known structural cerebrovascular lesion, known intracranial neoplasm, ischemic stroke within 3 months, active bleeding (excluding menses), and 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: o ✓ Alteplase: 15-mg intravenous (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) o ✓ Reteplase: 10 units IV over 2 minutes, followed 30 minutes later with another 10 units IV over 2 minutes o ✓ Tenecteplase: A single IV bolus dose administered as 30 to 50 mg over 5 to 10 seconds, based on body weight. o ✓ Streptokinase: 1.5 million units in 50 mL of normal saline or 5% dextrose in water IV over 60 minutes 3  Intracranial hemorrhage (ICH) and major bleeding are the most serious side effects of fibrinolytics. 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 receiving fibrinolytic therapy. Give non–enteric-coated aspirin (which may be chewed for more rapid effect) 162 to 325 mg 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 STEMI 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 are oral agents that 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. Doses are as follows: o ✓ 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. o ✓ Prasugrel: 60-mg oral loading dose followed by 10 mg orally once daily for patients weighing 60 kg (132 lb) or more. Consider 5 mg once daily for patients weighing less than 60 kg. o ✓ Ticagrelor: 180-mg oral loading dose in patients undergoing PCI, followed by 90 mg orally twice daily. Cangrelor is an IV drug indicated as an adjunct to PCI to reduce periprocedural MI, repeat revascularization, and stent thrombosis in patients not receiving oral P2Y12 inhibitors or planned GPIs. The dose is 30 mcg/kg IV bolus prior to PCI 4  followed by 4 mcg/kg/min infusion for duration of PCI or 2 hours, whichever is longer. A P2Y12 receptor inhibitor in addition to aspirin is recommended for all patients with STEMI. For patients undergoing primary PCI, clopidogrel, prasugrel, ticagrelor, or IV cangrelor should be given in addition to aspirin to prevent subacute stent thrombosis and longer-term CV events. The recommended duration of P2Y12 inhibitors for a patient undergoing PCI (either STEMI or NSTE-ACS) is at least 12 months for patients receiving either a bare metal or drug-eluting stent. If elective CABG surgery is planned, withhold clopidogrel and ticagrelor for 5 days prior, and prasugrel at least 7 days prior, to reduce risk of postoperative bleeding, unless the need for revascularization outweighs the bleeding risk. The hold time for urgent surgery is 24 hours. In STEMI patients 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 STEMI who do not undergo reperfusion therapy with either primary PCI or fibrinolysis, clopidogrel (added to aspirin) is the preferred P2Y12 inhibitor 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 not receiving fibrinolytics. Glycoprotein IIb/IIIa Receptor Inhibitors GPIs 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 STEMI undergoing primary PCI who are treated with UFH. Do not administer GPIs to patients with STEMI who will not be undergoing PCI. Abciximab: 0.25-mcg/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 GPI 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 of GPIs. Do not use GPIs in patients with a history of hemorrhagic stroke or recent ischemic stroke. Risk of bleeding is 5  increased in patients with chronic kidney disease; reduce the dose of eptifibatide and tirofiban in renal impairment. 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 with fibrinolytics is 60 units IV bolus (maximum 4000 units), followed by constant IV infusion of 12 units/kg/h (maximum 1000 units/h). Titrate to maintain a target activated partial thromboplastin time (aPTT) of 1.5 to 2 times control (50–70 seconds) for STE-ACS with fibrinolytics. 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. Continue for 48 hours or until the end of PCI. Enoxaparin dose is 1 mg/kg subcutaneous (SC) every 12 hours (creatinine clearance [Clcr] ≥30 mL/min) or once every 24 hours if impaired renal function (Clcr 15–29 mL/min). For patients with STEMI 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 STEMI 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 or 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 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 in the hours and days after an MI. 6  Because of an early risk of cardiogenic shock in susceptible patients, β-blockers (particularly when given IV) should be limited to patients who present with hypertension or signs of myocardial ischemia and do not have signs or symptoms of acute HF. Patients already taking β-blockers can continue taking them. Usual doses of β-blockers, with target resting heart rate of 50 to 60 beats/min: o ✓ Metoprolol: 5 mg by slow (over 1–2 minutes) IV bolus, repeated every 5 minutes for total initial dose of 15 mg, followed in 1 to 2 hours by 25 to 50 mg orally every 6 hours. If a very conservative regimen is desired, reduce initial doses to 1 to 2 mg. If appropriate, initial IV therapy may be omitted and treatment started with oral dosing. o ✓ 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. o ✓ 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 (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 ischemic discomfort, HF, or uncontrolled high BP. The usual dose is 5 to 10 mcg/min by continuous infusion, titrated up to 75 7  to 100 mcg/min until relief of symptoms or limiting side effects (eg, headache or hypotension). Discontinue IV infusion after 24 to 48 hours. 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 STEMI, 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 ACS 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. o ✓ Diltiazem: 120 to 360 mg sustained release orally once daily o ✓ Verapamil: 180 to 480 mg sustained release orally once daily o ✓ Amlodipine: 5 to 10 mg orally once daily EARLY PHARMACOTHERAPY FOR NSTE-ACS Early pharmacotherapy for NSTE-ACS is similar to that for STEMI (FIG. 5–3). 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 GPI (optional with either UFH or enoxaparin but should be avoided with bivalirudin). Administer a P2Y12 inhibitor to all patients; choice and timing depend on the interventional approach selected. 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. Never administer fibrinolytic therapy in NSTE-ACS. 8 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, fondaparinux, or bivalirudin. If an initial ischemia-guided 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 units IV bolus (maximum 4000 units), followed by a continuous IV infusion of 12 units/kg/h (maximum 1000 units/h). Titrate the dose to maintain aPTT between 1.5 and 2 times control. P2Y12 Inhibitors A P2Y12 receptor inhibitor (plus aspirin) is recommended for most patients with NSTE-ACS. They are the preferred antiplatelet agents because of efficacy and ease of use, resulting in decreased use of IV antiplatelet agents such as GPIs. With an ischemia-guided approach, either ticagrelor (preferred) or clopidogrel (300– 600 mg loading dose followed by 75 mg daily) can be used with low-dose aspirin and continued for up to 12 months. If an invasive management strategy is selected, either ticagrelor (preferred) or clopidogrel can be used either prehospital or in the ED. After PCI in patients not already treated with a P2Y12 inhibitor, clopidogrel, prasugrel or ticagrelor can be used and should be initiated at the time of or within 1 hour after PCI and continued for at least 12 months. 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 9  The role of GPIs in NSTE-ACS is diminishing as P2Y12 inhibitors are used earlier, and bivalirudin is often selected for early interventional approaches. 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 receiving a conservative management strategy, there is no role for routine GPIs 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 patients with NSTE- ACS within 24 hours of hospital admission. Benefits are assumed to be similar to those seen in patients with STEMI. 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 for STE-ACS, CCBs should be limited to patients with certain contraindications to β-blockers and those with continued ischemia despite β-blocker and nitrate therapy. Diltiazem and verapamil are preferred unless the patient has LV dysfunction, bradycardia, or heart block; amlodipine or felodipine is preferred in those situations. Immediate-release nifedipine is contraindicated. PHARMACOTHERAPY For all ACS patients, treat and control modifiable risk factors such as hypertension, dyslipidemia, obesity, smoking, and diabetes mellitus (DM). Start pharmacotherapy that has been proven to decrease mortality, HF, reinfarction or stroke, and stent thrombosis prior to hospital discharge for secondary prevention. After an 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. Chronic aspirin doses should not exceed 81 mg/day. 10  Start an oral ACE inhibitor early (within 24 hours) and continue indefinitely in all patients after MI to reduce mortality, decrease reinfarction, and prevent HF. Use a low initial dose and titrate to the dose used in clinical trials if tolerated. For example: o ✓ Captopril: 6.25 to 12.5 mg initially; target dose 50 mg two or three times daily o ✓ Enalapril: 2.5 to 5 mg initially; target dose 10 mg twice daily o ✓ Lisinopril: 2.5 to 5 mg initially; target dose 10 to 20 mg once daily o ✓ Ramipril: 1.25 to 2.5 mg initially; target dose 5 mg twice daily or 10 mg once daily o ✓ 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: o ✓ Candesartan: 4 to 8 mg initially; target dose 32 mg once daily o ✓ Valsartan: 40 mg initially; target dose 160 mg twice daily o ✓ Losartan: 12.5 to 25 mg initially; target dose 100 mg once daily All patients, regardless of LDL-cholesterol level, should ideally be prescribed a high- intensity statin. Patients over 75 years of age may be prescribed a moderate-intensity statin. Continue a β-blocker for at least 3 years in patients with normal LV function and indefinitely in patients with LVEF of 40% or less. 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 1 year in most patients with STEMI or NSTE- ACS. For patients with STEMI managed with fibrinolytics, continue clopidogrel for at least 14 days and ideally 1 year. New guidelines indicate that it is reasonable to continue dual antiplatelet therapy after 12 months in patients with STEMI and NSTE- ACS who were medically treated, who received fibrinolytics, or who had a PCI if they are not at high risk of bleeding and have not had overt bleeding. To reduce mortality, consider an aldosterone antagonist (eplerenone or spironolactone) within the first 7 days after MI in all patients already receiving an ACE inhibitor (or angiotensin receptor blocker) and a β-blocker and have an LVEF of 40% or less and either HF symptoms or DM. The drugs are continued indefinitely. o ✓ Eplerenone: 25 mg initially; target dose 50 mg once daily o ✓ Spironolactone: 12.5 mg initially; target dose 25 to 50 mg once daily 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 ito reduce CHD events after MI and are not used in ACS patients who have undergone 11  revascularization unless the patient has stable ischemic heart disease or significant coronary stenoses that were not revascularized. EVALUATION OF THERAPEUTIC OUTCOMES Monitoring parameters for efficacy for both STEMI 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. 12