A 45-year-old man is brought to a rural emergency department due to severe chest pain, sweating, and nausea. The symptoms began suddenly an hour ago. He has no significant medical history. His father died at age 50 after experiencing sudden-onset chest pain. The patient smokes a pack of cigarettes daily. He does not take any medications and has no known drug allergies. Examination shows normal heart sounds and breath sounds. ECG shows sinus tachycardia with ST segment elevation in leads II, III, and aVF. Medical management for the patient's acute condition is initiated. After initial treatment, the chest pain decreases in intensity and a reperfusion complex ventricular arrhythmia emerges. The arrhythmia is asymptomatic and resolves spontaneously. Which of the following drugs is most likely responsible for rapid reperfusion in this patient?
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This patient had an ST-elevation myocardial infarction (STEMI) and, following medical treatment, experienced symptomatic improvement and reperfusion-related arrhythmia; this is most likely the result of fibrinolytic (thrombolytic) therapy. Fibrinolytic agents (eg, alteplase) are indicated in patients with acute STEMI who cannot receive percutaneous coronary intervention in a timely manner. Administration of these agents leads to breakdown of fibrin clot and often restoration of myocardial perfusion; some patients develop a self-limiting reperfusion-related arrhythmia (most commonly an accelerated idioventricular rhythm).
In the fibrinolytic pathway, tissue plasminogen activator (tPA) is released by the endothelium and cleaves plasminogen to form plasmin. Plasmin then acts to both degrade individual fibrinogen molecules and break down fibrin clot that has already formed. The breakdown of fibrin clot leads to elevated levels of fibrin split products (eg, d-dimer) in the blood.
Pharmacologic fibrinolytic agents that are used clinically include streptokinase and recombinant forms of tPA (eg, alteplase, tenecteplase). All of these agents inherently increase bleeding risk and are contraindicated in patients with increased risk of bleeding complications (eg, recent hemorrhagic stroke).
(Choices B and C) Apixaban is a direct factor Xa inhibitor used in the treatment and prevention of venous thromboembolism, and argatroban is a direct thrombin inhibitor used to treat heparin-induced thrombocytopenia. Both of these drugs are anticoagulants; neither causes fibrinolysis or is typically used in the treatment of STEMI.
(Choices D and F) Aspirin inhibits cyclooxygenase to reduce thromboxane levels, and P2Y12 receptor blockers (eg, clopidogrel, prasugrel) prevent the binding of adenosine diphosphate to platelets; both actions lead to irreversible inhibition of platelet aggregation. These drugs are used together in acute STEMI to prevent the development of additional platelet thrombus; however, they do not cause lysis of existing thrombus.
(Choice E) Heparin potentiates the activity of antithrombin III to inhibit thrombin and factor Xa and exert an anticoagulation effect. Heparin is used in acute STEMI to prevent further progression of clot formation, but it does not cause thrombolysis.
(Choice G) Statins (eg, rosuvastatin) are used for acute STEMI as they may stabilize atherosclerotic plaques, reduce vascular inflammation, and promote long-term regression of atherosclerosis. However, they do not cause thrombolysis.
Educational objective:
In the fibrinolytic pathway, tissue plasminogen activator (tPA) converts plasminogen to plasmin, which then breaks down fibrin clot. The administration of a tPA analogue (eg, alteplase, tenecteplase, streptokinase) triggers fibrinolysis and can restore myocardial perfusion in patients with ST-elevation myocardial infarction who cannot undergo timely percutaneous coronary intervention.