Unstable angina / non ST elevation myocardial infarction GPIIb/IIIa inhibitor


 * Associate Editors-in-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Smita Kohli, M.D.

Glycoprotein IIb/IIIa Inhibitors in the Management of Unstable angina /NSTEMI
Three agents currently available are Abciximab, Eptifibatide and Tirofiban, all three of which are now included by the ACC/AHA guidelines for use in PCI.

Mechanism of action:
 * GP IIb/IIIa inhibitors inhibit the fibrinogen-mediated cross linkage of platelets, which is the final common pathway of platelet aggregation.

Clinical trial data:
 * ISAR-REACT 2 trial studied Abciximab in NSTEMI patients. This was a multicenter, randomized, double-blind, placebo-controlled study enrolling 2022 patients with non-ST-segment elevation ACS undergoing PCI. Results showed that Abciximab reduces the risk of adverse events in patients with non-ST-segment elevation ACS undergoing PCI after pretreatment with 600 mg of clopidogrel.
 * Most recently, EARLY ACS trial revealed that in patients who had acute coronary syndromes without ST-segment elevation, the use of eptifibatide 12 hours or more before angiography was not superior to the provisional use of eptifibatide after angiography. The early use of eptifibatide was associated with an increased risk of non-life-threatening bleeding and need for transfusion. Potential benefit with this class of drugs also led to study of oral GP IIa/IIIb inhibitors.
 * A major study involving Orbofiban(an oral GP IIb/IIIa inhibitor) failed to demonstrate improved outcomes and was associated with increased mortality.

Indications:
 * The benefits provided by abciximab appear to be confined to patients presenting with an elevated troponin level.
 * The benefit of GP IIb/IIIa inhibition appears greater when used in high-risk patients and in those with ST segment changes.
 * The benefit was also seen in high risk patients with or without revascularization.

Contraindications:
 * Abciximab is not recommended if PCI is not planned. Eptifibatide and Tirofiban are preferred agents when delay in coronary angiography and PCI is anticipated.

Dosing:
 * All three agents are for intravenous usage and are given by bolus and continuous infusion.
 * Optimal timing of GP IIb/IIIa inhibition remains controversial with no clear data available from current trials. More so, most of the trials related to timing of GP IIa/IIIb inhibitors involve patients with STEMI and hence cannot be applied to all ACS patients.

Disadvantage of GP IIb/IIIa inhibitors:
 * A major side effect of GP IIb/IIIa inhibitors is thrombocytopenia and hence increased bleeding. Therefore, platelet monitoring is indicated during its use.

==ACC / AHA Guidelines for Antiplatelet therapy in Unstable Angina/NSTEMI (DO NOT EDIT) ==

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Class I
1. Patients with definite Unstable angina / NSTEMI at medium or high risk and in whom an initial invasive strategy is selected should receive dual-antiplatelet therapy on presentation. (Level of Evidence: A) ASA should be initiated on presentation. (Level of Evidence: A)The choice of a second antiplatelet therapy to be added to ASA on presentation includes 1 of the following:

Before PCI:
 * Clopidogrel (Level of Evidence: B); or
 * An IV GP IIb/IIIa inhibitor. (Level of Evidence: A) IV eptifibatide or tirofiban are the preferred GP IIb/IIIa inhibitors.

At the time of PCI:
 * Clopidogrel if not started before PCI (Level of Evidence: A); or
 * Prasugrel (Level of Evidence: B); or
 * An IV GP IIb/IIIa inhibitor. (Level of Evidence: A)

2. For Unstable angina / NSTEMI patients in whom an initial invasive strategy is selected, antiplatelet therapy in addition to aspirin should be initiated before diagnostic angiography (upstream) with either clopidogrel (loading dose followed by daily maintenance dose) or an intravenous GP IIb/IIIa inhibitor. (Level of Evidence: A) Abciximab as the choice for upstream GP IIb/IIIa therapy is indicated only if there is no appreciable delay to angiography and PCI is likely to be performed; otherwise, IV eptifibatide or tirofiban is the preferred choice of GP IIb/IIIa inhibitor. (Level of Evidence: B)

3. For Unstable angina / NSTEMI patients in whom an initial conservative strategy is selected, if recurrent symptoms/ischemia, HF, or serious arrhythmias subsequently appear, then diagnostic angiography should be performed. (Level of Evidence: A). Either an IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban [Level of Evidence: A]) or clopidogrel (loading dose followed by daily maintenance dose [Level of Evidence: B]) should be added to ASA and anticoagulant therapy before diagnostic angiography (upstream). (Level of Evidence: C)

Class IIa
1. For Unstable angina / NSTEMI patients in whom an initial conservative strategy is selected and who have recurrent ischemic discomfort with clopidogrel, ASA, and anticoagulant therapy, it is reasonable to add a GP IIb/IIIa antagonist before diagnostic angiography. (Level of Evidence: C)

2. For Unstable angina / NSTEMI patients in whom an initial invasive strategy is selected, it is reasonable to omit administration of an IV GP IIb/IIIa inhibitor if bivalirudin is selected as the anticoagulant and at least 300 mg of clopidogrel was administered at least 6 hours earlier than planned catheterization or PCI. (Level of Evidence: B)

Class IIb
1. For Unstable angina / NSTEMI patients in whom an initial conservative (i.e., noninvasive) strategy is selected, it may be reasonable to add eptifibatide or tirofiban to anticoagulant and oral antiplatelet therapy. (Level of Evidence: B)

2. The use of upstream GP IIb/IIIa inhibitors may be considered in high-risk Unstable angina / NSTEMI patients already receiving ASA and a thienopyridine who are selected for an invasive strategy, such as those with elevated troponin levels, diabetes, or significant ST-segment depression, and who are not otherwise at high risk for bleeding. (Level of Evidence: B)

Class III
No Benefit

1. Abciximab should not be administered to patients in whom PCI is not planned. (Level of Evidence: A)

2. In Unstable angina / NSTEMI patients who are at low risk for ischemic events (e.g., TIMI risk score ≥2) or at high risk of bleeding and who are already receiving ASA and clopidogrel, upstream GP IIb/IIIa inhibitors are not recommended. (Level of Evidence: B)}}