Acute Coronary Syndrome PDF

Acute coronary syndrome (ACS) includes all syndromes compatible with acute Clinical Pharmacy and myocardial...

Acute coronary syndrome (ACS) includes all syndromes compatible with acute Clinical Pharmacy and myocardial ischemia resulting from imbalance between myocardial oxygen demand and supply. Acute Coronary Therapeutics PHCP 311 ACS is classified according to electrocardiographic (ECG) changes into: Syndrome Our Lady of Fatima University Ø A. ST segment- elevation myocardial infarction College of Pharmacy (STEMI) Ø B. non–ST-segment-elevation ACS (NSTE-ACS), which includes: Ø non–ST-segment-elevation MI (NSTEMI) Ø unstable angina (UA). Pathophysiology Ø Endothelial dysfunction, inflammation, and formation of fatty Subtypes of MI are based on etiology: streaks contribute to development of atherosclerotic coronary artery plaques. Ø Type 1: Rupture, fissure, or erosion of an Ø With rupture of an atherosclerotic plaque, exposure of collagen atherosclerotic plaque (90% of cases); and tissue factor induces platelet adhesion and activation, Ø Type 2: Reduced myocardial oxygen supply or promoting release of adenosine diphosphate (ADP) and increased demand in the absence of a coronary thromboxane A2 from platelets, leading to vasoconstriction and platelet activation. artery process; Ø A change in the conformation of the glycoprotein IIb/IIIa surface Ø Type 3: MI resulting in death without the receptors of platelets occurs that cross-links platelets to each possibility of measuring biomarkers; other through fibrinogen bridges. Ø Simultaneously, activation of the extrinsic coagulation cascade Ø Type 4: MI associated with percutaneous occurs as a result of exposure of blood to the thrombogenic lipid coronary intervention (PCI; Type 4a) or stent core and endothelium, which are rich in tissue factor. thrombosis (Type 4b); Ø This leads to formation of a fibrin clot composed of fibrin Ø Type 5: MI associated with coronary artery strands, cross-linked platelets, and trapped red blood cells. bypass graft (CABG) surgery Clinical Presentation Ø Ventricular remodeling after MI is Ø The predominant symptom is midline anterior characterized by left ventricular (LV) dilation chest pain (usually at rest), severe new-onset and reduced pumping function, leading to angina, or increasing angina that lasts at least 20 heart failure (HF). minutes. Ø Complications of MI include cardiogenic Ø Discomfort may radiate to the shoulder, down the shock, HF, valvular dysfunction, arrhythmias, left arm, to the back, or to the jaw. Accompanying symptoms may include nausea, vomiting, pericarditis, stroke secondary to LV thrombus diaphoresis, and shortness of breath. embolization, venous thromboembolism, LV Ø No specific features indicate ACS on physical free-wall or septal rupture, aneurysm examination. However, patients with ACS may formation, and ventricular and atrial present with signs of acute decompensated HF or tachyarrhythmias. arrhythmias. Ø Obtain 12-lead ECG Diagnosis of MI is confirmed with detection of rise and/or within 10 minutes of fall of cardiac biomarkers (mainly troponin T or I) with at presentation least one value above the 99th percentile of the upper Ø ST-segment reference limit and at least one of the following: depression, and T- wave inversion Ø Symptoms of ischemia Appearance of a new Ø Sew significant ST-segment–T-wave changes or new left bundle-branch block left bundle-branch block; with chest discomfort is Ø Pathological Q waves; highly specific for acute Ø Imaging evidence of new loss of viable myocardium or MI. new regional wall motion abnormality. Ø Typically, a blood sample is obtained once in the emergency department, then 3 to 6 hours after symptom onset. Goals of Treatment: Evaluation of the acute coronary syndrome patient Ø Short term goal: Ø 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), Ø Prevention of death and other complications, Normal Pattern Ø Prevention of coronary artery reocclusion, Ø Relief of ischemic chest discomfort, Ø Resolution of ST-segment and T-wave changes on ECG. Ø Long term goal: Ø control of cardiovascular (CV) risk factors, prevention of additional CV events, and improvement in quality of life  Ø Patients with STEMI are at high risk of death, so initiate immediate efforts to reestablish coronary perfusion and adjunctive pharmacotherapy. Ø 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. Ø For patients with NSTE-ACS, practice guidelines recommend an early (within 24 hours) invasive strategy with left heart catheterization, 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. ST Segment Elevation A Options after coronary angiography also All patients with STEMI and without contraindications include medical management alone or CABG surgery. should receive within the first day of hospitalization B Clopidogrel preferred P2Y12 inhibitor when fibrinolytic therapy is utilized. No loading dose and preferably in the emergency department: recommended if age older than 75 years. C Given for up to 48 hours or until ☐ A. Intranasal oxygen (if oxygen saturation is low), revascularization. D Given for the duration of hospitalization, up to 8 days or until revascularization. ☐ B. Sublingual (SL) nitroglycerin (NTG), E If pretreated with UFH, stop UFH infusion for 30 minutes prior to administration of bivalirudin (bolus plus infusion). ☐ C. Aspirin F In patients with STEMI receiving a fibrinolytic or who do not receive reperfusion therapy, administer clopidogrel for at least 14 days and ☐ D. P2Y12 platelet inhibitor ideally up to 1 year. (ACE, angiotensin-converting enzyme; ARB, ☐ E. anticoagulation with bivalirudin, unfractionated angiotensin receptor blocker; ASA, aspirin; CI, contraindication; FMC, first medical contact; heparin (UFH), enoxaparin, or fondaparinux GPI, glycoprotein IIb/IIIa inhibitor; IV, intravenous; MI, myocardial infarction; NTG, (depending on reperfusion strategy). nitroglycerin; PCI, percutaneous coronary intervention; SC, subcutaneous; SL, sublingual; UFH, unfractionated heparin.) Fibrinolytic therapy Contraindication for Fibrinolytics Ø Indicated in patients with STEMI who present Ø Any prior intracranial hemorrhage, known within 12 hours of the onset of chest discomfort to structural cerebrovascular lesion (eg, AV a hospital not capable of primary PCI and have at least a 1-mm STE in two or more contiguous ECG malformation), known intracranial neoplasm, leads, have no absolute contraindications to ischemic stroke within 3 months, active fibrinolytic therapy and cannot be transferred and bleeding (excluding menses), and significant undergo primary PCI within 120 minutes of closed head or facial trauma within 3 months. medical contact. Ø Primary PCI is preferred in these situations. Ø Fibrinolytic use between 12 and 24 hours after symptom onset should be limited to patients with ongoing ischemia. Ø Preference: Fibrin specific > Streptokinase  Aspirin Ø Treat eligible patients as soon as possible, but preferably Ø Administer aspirin to all patients without contraindications within 30 minutes from the time they present to the within 24 hours before or after hospital arrival. emergency department, with one of the following regimens: Ø It provides additional mortality benefit in patients receiving fibrinolytic therapy. Ø Alteplase Ø Give non–enteric-coated aspirin (which may be chewed for Ø Reteplase more rapid effect) 162 to 325 mg regardless of the Ø Tenecteplase reperfusion strategy being considered Ø Streptokinase Ø PCI not previously taking aspirin should receive 325- Ø Intracranial Hemorrhage mg non–enteric-coated aspirin Ø Most serious ADR of fibrinolytics Ø Maintenance dose: 75- 165 mg daily, if given with ADP inhibitor, 81 mg (low dose) is preferred to avoid bleeding Ø Fibrin specific > streptokinase Ø Discontinue NSAIDs and COX inhibitors at the time of Ø Systemic bleeding STEMI Ø Streptokinase > Fibrin specific Ø Increase risk of death, reinfarction and heart failure Ø ADR: dyspepsia, nausea, bleeding Platelet P2Y12 Inhibitors ( ADP inhibitors) Glycoprotein IIb/IIIa Receptor Inhibitors Ø Prevents binding of ADP to the receptor and subsequent Ø GPIs block the final common pathway of platelet aggregation, namely, cross- expression of platelet GP IIb/IIIa receptors, reducing linking of platelets by fibrinogen bridges between the GP IIb and IIIa receptors on platelet aggregation. the platelet surface Ø Oral: Clopidogrel, Prasugrel, Ticagrelor Ø Do not administer GPIs to patients with STEMI who will not be undergoing Ø IV: Cangrelor PCI. ☐ In adults younger than 75 years receiving fibrinolytics, o Abciximab: 0.25-mg/kg IV bolus given 10 to 60 minutes before the the first dose of clopidogrel can be a 300-mg loading start of PCI, followed by 0.125 mcg/kg/min (maximum 10 mcg/min) for dose 12 hours. o 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. Ø ADP inhibitor + Aspirin: recommended for all STEMI patients o Tirofiban: 25-mcg/kg IV bolus, then 0.15 mcg/kg/min up to 18 to 24 hours after PCI. Ø ARD: Ø Contraindications: Ø Clopidogrel: hypersensitivity, Thrombocytopenic Ø Px with history of hemorrhagic stroke or recent ischemic stroke. purpura Ø Px with CKD Ø Ticagrelor: Nausea, diarrhea, dyspnea (19%), o Reduce dose of Epfibatide and tirfiban brady arrhythmias Ø ADR: immune-mediated thrombocytopenia Anticoagulants β-Adrenergic Blocker Ø Either UFH or bivalirudin is preferred for patients undergoing Ø Blockade of β1 receptors in the myocardium primary PCI, whereas for fibrinolysis, either UFH, enoxaparin, or o reduces heart rate, myocardial contractility, and BP, thereby fondaparinux may be used. decreasing myocardial oxygen demand Ø UFH: initial dose for primary PCI is 50 to 70 units/kg IV bolus o Reduced heart rate increases diastolic time, thus improving if a GPI is planned and 70 to 100 units IV bolus if no GPI is ventricular filling and coronary artery perfusion. planned; o Reduce risk for recurrent ischemia, infarct size, reinfarction, and Ø Enoxaparin: 1 mg/kg subcutaneous (SC) every 12 hours ventricular arrhythmias in the hours and days after an MI (creatinine clearance [Clcr] ≥30 mL/min) or once every 24 Ø Limited to patients who present with hypertension or signs of myocardial hours if impaired renal function (Clcr 15–29 mL/min). ischemia and do not have signs or symptoms of acute HF. Ø Bivalirudin dose for PCI in STEMI is 0.75 mg/kg IV bolus, o Risk of Cardiogenic shock Ø Patients already taking β-blockers can continue taking them. followed by 1.75 mg/kg/h infusion. Discontinue at the end of Ø Metoprolol, Propranolol, Atenolol PCI o Continue β-blockers for at least 3 years in patients with normal LV Ø Fondaparinux dose is 2.5 mg IV bolus followed by 2.5 mg SC function and indefinitely in patients with LV systolic dysfunction and once daily starting on hospital day 2. LVEF of 40% or less. Ø For patients undergoing PCI, discontinue anticoagulation o ADR: hypotension, acute HF, bradycardia, and heart block. immediately after the procedure. Statins Nitrates Ø NTG causes venodilation, which lowers preload and myocardial oxygen Ø Administer a high-intensity statin demand. Ø Arterial vasodilation may lower BP, thereby reducing myocardial oxygen (atorvastatin 80 mg or rosuvastatin 40 mg) demand. to all patients prior to PCI (regardless of prior Ø Arterial dilation also relieves coronary artery vasospasm and improves myocardial blood flow and oxygenation lipid-lowering therapy) to reduce the frequency Ø Immediately upon presentation, administer one SL NTG tablet (0.4 mg) every 5 minutes for up to three doses to relieve chest pain and of periprocedural MI (Type IVa MI) following myocardial ischemia. Ø Intravenous NTG is indicated for patients with an ACS who do not have PCI a contraindication and who have persistent ischemic discomfort, HF, or uncontrolled high BP. ☐ Oral nitrates play a limited role in ACS Ø ADR: tachycardia, flushing, headache, and hypotension Ø C/I: Patients taking PD5-I o sildenafil or vardenafil within the prior 24 hours o tadalafil within the prior 48 hours Calcium Channel Blockers Ø After STEMI, calcium channel blockers (CCBs) are used for relief of ischemic symptoms in patients who have contraindications to β-blockers. Ø Non dihydropyridine ( diltiazem, verapamil) > dihydropyridine ØExcept: LV systolic dysfunction, bradycardia, or heart block. ☐Give Amlodipine or Felodipine ☐Avoid Nifedipine ☐causes reflex sympathetic activation tachycardia, and worsened myocardial ischemia. Important Precautions Ø Early pharmacotherapy for NSTE-ACS is similar to that for STEMI. Ø 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). Ø 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). Ø Administer a P2Y12 inhibitor to all patients; choice and timing depend on the interventional approach selected. Ø Give IV β-blockers and IV NTG to select patients. Ø Initiate oral β-blockers within the first 24 hours in patients without cardiogenic shock. Ø Give morphine to patients with refractory angina Ø Never administer fibrinolytic therapy in NSTE-ACS. Aspirin Anticoagulants Ø Aspirin reduces risk of death or MI by Ø Early invasive approach with early coronary approximately 50% compared with no angiography and PCI, administer UFH, antiplatelet therapy in patients with NSTE- enoxaparin, fondaparinux, or bivalirudin. ACS. Ø If Initial ischemia-guided strategy: (no coronary angiography or revascularization), enoxaparin, UFH, or low-dose fondaparinux is recommended Ø Continue therapy for at least 48 hours for UFH, until the patient is discharged from the hospital P2Y12 Inhibitors Nitrates Ø A P2Y12 receptor inhibitor (plus aspirin) is Ø Administer SL NTG followed by IV NTG to recommended for most patients with NSTE-ACS. Ø They are the preferred antiplatelet agents because patients with NSTE-ACS and ongoing of efficacy and ease of use, resulting in decreased ischemia, HF, or uncontrolled high BP. use of IV antiplatelet agents such as GPIs Ø Continue IV NTG for approximately 24 hours Ø invasive management strategy: Ticagrelor or after ischemia relief. clopidogrel prehospital or in ED Ø Following PCI, continue dual oral antiplatelet therapy for at least 12 months. Ø initial conservative strategy: clopidogrel or ticagrelor can be administered in addition to aspirin. ☐ Continue dual antiplatelet therapy for at least 12 months. β-Blockers Calcium Channel Blockers Ø In the absence of contraindications, Ø limited to patients with certain administer oral β-blockers to patients with contraindications to β-blockers and those with NSTE-ACS within 24 hours of hospital continued ischemia despite β-blocker and admission. nitrate therapy. Ø Continue β-blockers indefinitely in patients Ø Diltiazem and verapamil are preferred unless with LVEF of 40% or less and for at least 3 the patient has LV dysfunction, years in patients with normal LV function. Ø Alternative: Amlodipine or Felodipine Ø C/I: Nifedipine SECONDARY PREVENTION FOLLOWING MI Ø 1. treat and control modifiable risk factors such as hypertension, dyslipidemia, obesity, smoking, and diabetes mellitus (DM). Ø 2. indefinite treatment with: A. Aspirin 81 mg/day (or clopidogrel if aspirin contraindications) B. ACE inhibitor or ARBs C. High-intensity statin D. β-blocker for at least 3 years in patients with normal LV function and indefinitely in patients with LVEF of 40% or less; o Alternative: CCBs E. P2Y12 inhibitor for at least 1 year in most patients with STEMI or NSTEACS. F. Short-acting SL NTG or lingual NTG spray, PRN for anginal relief