Acute Coronary Syndromes Overview

Acute Coronary Syndromes (ACS)

• ACS encompasses all syndromes compatible with acute myocardial ischemia stemming from an imbalance between myocardial oxygen demand and supply.
• Classified into:
  • ST-segment-elevation myocardial infarction (STEMI)
  • Non–ST-segment-elevation ACS (NSTE-ACS)
    • Non–ST-segment-elevation MI (NSTEMI)
    • Unstable angina (UA)

Pathophysiology

• Endothelial dysfunction, inflammation and fatty streaks contribute to the development of atherosclerotic coronary artery plaques.
• Rupture of a plaque exposes collagen and tissue factor, inducing platelet adhesion and activation.
• Platelets release adenosine diphosphate (ADP) and thromboxane A2, leading to vasoconstriction and activation.
• Glycoprotein IIb/IIIa receptor conformation changes, enabling platelets to cross-link through fibrinogen bridges.
• Activation of the extrinsic coagulation cascade occurs due to exposure of blood to the thrombogenic lipid core and endothelium.
• This leads to the formation of a fibrin clot composed of fibrin strands, platelets and trapped red blood cells.
• Ventricular remodeling post-MI is characterized by left ventricular (LV) dilation and reduced pumping function, leading to heart failure (HF).

Clinical Presentation

• Predominant symptom is midline anterior chest pain, often at rest.
• Severe, new-onset angina or increasing angina lasting at least 20 minutes.
• Discomfort may radiate to the shoulder, left arm, back or jaw.
• Accompanying symptoms can include nausea, vomiting, diaphoresis and shortness of breath.

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 exhibit no ECG changes, requiring biochemical markers and coronary artery disease risk factors evaluation.
• MI diagnosis is confirmed with rising and/or falling cardiac biomarkers (mainly troponin T or I) along with ECG changes.
• Blood samples are typically taken once in the emergency department and again 3 to 6 hours after symptom onset.

Treatment Goals

• Short-term goals include:
  • Early restoration of blood flow to the infarct-related artery.
  • Prevention of death and other complications.
  • Prevention of coronary artery reocclusion.
  • Relief of ischemic chest discomfort.
  • Resolution of ST-segment and T-wave changes on ECG.
• Long-term goals involve controlling cardiovascular (CV) risk factors, preventing additional CV events and enhancing quality of life.

Nonpharmacologic Therapy

• For STEMI patients 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 preferred treatment.
• For NSTE-ACS patients, practice guidelines recommend early (within 24 hours) coronary angiography and revascularization with either PCI or CABG surgery as early treatment for high-risk patients.

Pharmacologic Therapy

• Fibrinolytics
  • Fibrinolytics are used to dissolve blood clots and restore blood flow to the heart.
  • They are given intravenously (IV) and should be administered as soon as possible after the onset of symptoms.
  • Available therapies include:
    • Alteplase
    • Reteplase
    • Tenecteplase
    • Streptokinase
  • ICH and major bleeding are the most serious side effects.
• Aspirin
  • Administer aspirin to all patients without contraindications within 24 hours before or after hospital arrival.
  • Provides additional mortality benefit in patients receiving fibrinolytic therapy.
  • Give non–enteric-coated aspirin 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.
  • Low-dose aspirin (81 mg daily) is preferred following PCI due to increased bleeding risk when combined with a P2Y12 inhibitor.
  • Discontinue other NSAIDs and COX-2 selective inhibitors at the time of STEMI.
  • The most frequent side effects of aspirin include dyspepsia and nausea.
• Unfractionated Heparin (UFH)
  • Administer IV UFH to all patients with STEMI or NSTE-ACS.
  • Titrate to maintain a target aPTT of 1.5 to 2 times control.
  • 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.
• Low-Molecular-Weight Heparin (LMWH)
  • Encoxaparin: 1 mg/kg SC every 12 hours (creatinine clearance [Clcr] ≥30 mL/min) or once every 24 hours if Clcr is impaired.
  • For STEMI receiving fibrinolytics: 30-mg IV bolus followed immediately by 1 mg/kg SC every 12 hours if younger than 75 years, 0.75 mg/kg SC every 12 hours for patients 75 years and older.
  • Continue enoxaparin throughout hospitalization or up to 8 days.
• Direct Thrombin Inhibitor
  • Bivalirudin: 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.
• Factor Xa Inhibitor
  • Fondaparinux: 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.
• β-Adrenergic Blockers
  • Benefits include reduced heart rate, myocardial contractility and BP, decreasing myocardial oxygen demand.
  • Reduce risk for recurrent ischemia, infarct size, reinfarction and ventricular arrhythmias.
  • Β-blockers (particularly IV) should be limited to patients presenting with hypertension or signs of myocardial ischemia who do not have signs/symptoms of acute HF.
  • Usual doses include:
    • Metoprolol
    • Propranolol
    • Atenolol
  • The most serious side effects early include hypotension, acute HF, bradycardia and heart block.
  • 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 to all patients prior to PCI, regardless of prior lipid-lowering therapy.
• Nitrates
  • NTG causes venodilation, lowering preload and myocardial oxygen demand.
  • Arterial vasodilation may lower BP, reducing myocardial oxygen demand.
  • Arterial dilation also relieves coronary artery vasospasm and improves myocardial blood flow and oxygenation.
  • Administer one SL NTG tablet (0.4 mg) every 5 minutes for up to three doses to relieve chest pain and myocardial ischemia.
  • IV NTG is indicated for patients with an ACS without contraindications and who have persistent ischemic discomfort, HF or uncontrolled high BP.

General Information

• Patients presenting with symptoms suggestive of ACS should undergo prompt evaluation and treatment.
• Timely and accurate diagnosis and management of ACS are crucial for improving patient outcomes and reducing mortality.