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Anticoagulant therapy in non-ST elevation acute coronary syndromes

Authors
Michael Simons, MD
Donald Cutlip, MD
A Michael Lincoff, MD
Section Editors
Christopher P Cannon, MD
Freek Verheugt, MD, FACC, FESC
Deputy Editor
Gordon M Saperia, MD, FACC

INTRODUCTION

Rupture of an atherosclerotic plaque is the usual initiating event in an acute coronary syndrome (ACS). Persistent thrombotic occlusion at the site of plaque rupture results in acute myocardial infarction. (See "The role of the vulnerable plaque in acute coronary syndromes".)

Thrombin activity at the site of plaque rupture may result in delayed or incomplete reperfusion of occluded vessels and contributes to reocclusion. Thrombin is a central mediator of clot formation through its activation of platelets, conversion of fibrinogen to fibrin, and activation of factor XIII, leading to fibrin cross-linking and clot stabilization. Anticoagulants, including heparins, direct thrombin inhibitors, and fondaparinux interfere with the activity of thrombin. (See "Overview of hemostasis".)

This topic will review the evidence that supports the use of parenteral anticoagulant therapy in all patients with an acute non-ST elevation ACS (NSTEACS), which includes both unstable angina and acute non-ST elevation myocardial infarction, and will provide recommendations for its use according to whether the patient receives reperfusion with percutaneous coronary intervention or no reperfusion therapy. Information regarding anticoagulant agents in ST elevation myocardial infarction and the role of antiplatelet therapy in NSTEACS is found elsewhere. (See "Anticoagulant therapy in acute ST elevation myocardial infarction" and "Antiplatelet agents in acute non-ST elevation acute coronary syndromes".)

CLASSIFICATION OF ANTICOAGULANT AGENTS

There are three classes of anticoagulants 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 MI. The most important is that the heparin-antithrombin (AT, formerly called antithrombin III) complex cannot bind or inactivate thrombin bound within a clot [1]. Such clot-bound thrombin acts as an important thrombogenic stimulus at a site of coronary thrombosis, particularly after clot disruption by fibrinolytic agents [2]. An additional concern with the administration of UFH has been heparin-induced thrombocytopenia (HIT). The risk is much lower but not absent with LMWH than with UFH and is not seen with the direct thrombin inhibitors or fondaparinux. (See "Anticoagulant therapy in acute ST elevation myocardial infarction", section on 'Classification of anticoagulant agents'.)

LMWH inactivates factor Xa, like UFH, but has a lesser effect on thrombin (figure 1). As a result, LMWH 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.

                      

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Literature review current through: Nov 2016. | This topic last updated: Mon Jan 04 00:00:00 GMT+00:00 2016.
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