Anticoagulant therapy in acute ST elevation myocardial infarction
- A Michael Lincoff, MD
A Michael Lincoff, MD
- Director, Center for Clinical Research
- Professor of Medicine
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
- Donald Cutlip, MD
Donald Cutlip, MD
- Section Editor — Interventional Cardiology
- Professor of Medicine
- Harvard Medical School
- Beth Israel Deaconess Medical Center
- Section Editors
- Freek Verheugt, MD, FACC, FESC
Freek Verheugt, MD, FACC, FESC
- Section Editor — Coronary Heart Disease
- Onze Lieve Vrouwe Gasthuis, Netherlands
- Christopher P Cannon, MD
Christopher P Cannon, MD
- Section Editor — Coronary Heart Disease
- Professor of Medicine
- Harvard Medical School
Acute myocardial infarction (MI) results from rupture of an atherosclerotic plaque, which leads to intraluminal thrombosis. Intraluminal thrombus impairs distal blood flow and may lead to myocardial ischemia or infarction. Intraluminal hemostasis is a dynamic process involving both clot formation and intrinsic fibrinolysis. The goal of antithrombotic therapy (the combination of anticoagulant and antiplatelet therapy) is to prevent clot extension and clot reformation in cases where the clot has undergone fibrinolysis either by intrinsic mechanisms, fibrinolytic treatment, or mechanical means. (See "The role of the vulnerable plaque in acute coronary syndromes" and "Overview of hemostasis".)
This topic will review the evidence that parenteral anticoagulant therapy is beneficial in all patients with acute ST-elevation MI (STEMI) and will provide recommendations for its use according to whether the patient receives fibrinolysis, primary percutaneous coronary intervention, or no reperfusion therapy. Information regarding anticoagulant agents in non-ST elevation acute coronary syndromes (unstable angina or non-ST elevation MI) and the role of antiplatelet therapy in STEMI is discussed separately. (See "Anticoagulant therapy in non-ST elevation acute coronary syndromes" and "Antiplatelet agents in acute ST elevation myocardial infarction".)
CLASSIFICATION OF ANTICOAGULANT AGENTS
There are three classes of anticoagulants (figure 1) that have been evaluated in the management of acute coronary syndromes:
●The heparins, including unfractionated heparin (UFH) and the low molecular weight heparins (LMWH), are indirect thrombin inhibitors that complex with antithrombin (AT, formerly known as AT III) and convert AT from a slow to a rapid inactivator of thrombin, factor Xa, and to a lesser extent, factors XIIa, XIa, and IXa. (See "Overview of hemostasis" and "Heparin and LMW heparin: Dosing and adverse effects".)
There are a number of intrinsic limitations to UFH therapy in patients with acute myocardial infarction (MI). The most important is that the heparin-antithrombin complex cannot bind or inactivate thrombin bound within a clot . Such clot-bound thrombin acts as an important thrombogenic stimulus at a site of coronary thrombosis, particularly after clot disruption by fibrinolytic agents . An additional concern with the administration of UFH has been heparin-induced thrombocytopenia (HIT). The risk is much lower with LMWH than with UFH and is not seen with the direct thrombin inhibitors or fondaparinux. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia" and "Management of heparin-induced thrombocytopenia".)
LMWH inactivates factor Xa, like UFH, but has a lesser effect on thrombin. As a result, LMWHs do not prolong the aPTT in a predictable fashion. They have a number of advantages over UFH, including a more predictable anticoagulant effect and a reduced likelihood of inducing immune-mediated thrombocytopenia.
●The direct thrombin inhibitors (eg, hirudin, bivalirudin, lepirudin) bind to and inactivate one or more of the active sites on the thrombin molecule . For patients with ST elevation MI, only bivalirudin is clinically used [4-7]. (See "Direct oral anticoagulants: Dosing and adverse effects", section on 'Direct thrombin inhibitors'.)
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- CLASSIFICATION OF ANTICOAGULANT AGENTS
- FIBRINOLYTIC THERAPY
- Anticoagulant compared to placebo
- UFH compared to LMWH
- Direct thrombin inhibitors
- PRIMARY PCI
- UFH compared to bivalirudin
- UFH compared to enoxaparin
- NO REPERFUSION THERAPY
- Unfractionated heparin
- Low molecular weight heparin
- ANTICOAGULANT REGIMENS
- RECOMMENDATIONS OF OTHERS
- SUMMARY AND RECOMMENDATIONS