Unstable angina NSTEMI Antiplatelet therapy recommendations

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The current most updated guidelines state that for UA/NSTEMI patients presenting to the hospital, aspirin should be administered immediately, and if the patient cannot take aspirin, another anti-platelet agent, namely clopidogrel or prasugrel (in PCI treated patients) should be given. UA/NSTEMI patients at moderate to high risk who will be undergoing PCI should be given dual antiplatelet therapy consisting of aspirin and one of the following; clopidogrel, ticagrelor, eptifibatide and prasugrel, depending on whether the second agent is given before or during PCI. Addtional situation specific guidelines are given below.

2012 ACCF/AHA Focused Update of the Guideline for the Management of Patients With Unstable Angina/Non–ST-Elevation Myocardial Infarction (Updating the 2007 Guideline and Replacing the 2011 Focused Update) (DO NOT EDIT)[1]

Antiplatelet therapy (DO NOT EDIT)[1]

Class I
"1. Aspirin should be administered to UA/NSTEMI patients as soon as possible after hospital presentation and continued indefinitely in patients who tolerate it.[2][3][4][5][6] (Level of Evidence: A)"
"2. A loading dose followed by daily maintenance dose of either clopidogrel[7][8][9] (Level of Evidence: C), prasugrel* (in PCI-treated patients)[10] (Level of Evidence: C), or ticagrelor**[11] (Level of Evidence: C) should be administered to UA/NSTEMI patients who are unable to take aspirin because of hypersensitivity or major GI intolerance."
"3. Patients with definite UA/NSTEMI at medium or high risk and in whom an initial invasive strategy is selected should receive dual antiplatelet therapy on presentation.[7][12][13][14] (Level of Evidence: A) Aspirin should be initiated on presentation.[2][15][16][4][5][6][17] (Level of Evidence: A) The choice of a second antiplatelet therapy to be added to aspirin on presentation includes 1 of the following:

a) Before PCI:

b) At the time of PCI:

"4. For UA/NSTEMI patients in whom an initial conservative (ie, noninvasive) strategy is selected, clopidogrel or Ticagrelor** (loading dose followed by daily maintenance dose) should be added to aspirin and anticoagulant therapy as soon as possible after admission and administered for up to 12 months.[18][24][7] (Level of Evidence: B)"
"5. For UA/NSTEMI patients in whom an initial conservative strategy is selected, if recurrent symptoms/ischemia, heart failure, or serious arrhythmias subsequently appear, then diagnostic angiography should be performed.[25][26] (Level of Evidence: A) Either an IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban[23][19][20] Level of Evidence: A), clopidogrel (loading dose followed by daily maintenance dose[7] Level of Evidence: B), or ticagrelor** (loading dose followed by daily maintenance dose[18] Level of Evidence: B) should be added to aspirin and anticoagulant therapy before diagnostic angiography (upstream). (Level of Evidence: C)"
"6. A loading dose of P2Y12 receptor inhibitor therapy is recommended for UA/NSTEMI patients for whom PCI is planned.*** Regimens should be 1 of the following:

a) Clopidogrel 600 mg should be given as early as possible before or at the time of PCI[27][28][29] (Level of Evidence: A) or

b) Prasugrel* 60 mg should be given promptly and no later than 1 hour after PCI once coronary anatomy is defined and a decision is made to proceed with PCI.[30] (Level of Evidence: B)

c) Ticagrelor** 180 mg should be given as early as possible before or at the time of PCI.[18] (Level of Evidence: B)"

"7. The duration and maintenance dose of P2Y12 receptor inhibitor therapy should be as follows:

a) In UA/NSTEMI patients undergoing PCI, either clopidogrel 75 mg daily[7][12], prasugrel* 10 mg daily[30], or ticagrelor** 90 mg twice daily[18] should be given for at least 12 months. (Level of Evidence: B)

b) If the risk of morbidity because of bleeding outweighs the anticipated benefits afforded by thienopyridine therapy, earlier discontinuation should be considered. (Level of Evidence: C)"

Class III: No Benefit
"1. Abciximab should not be administered to patients in whom PCI is not planned.[23][22] (Level of Evidence: A)"
"2. In UA/NSTEMI patients who are at low risk for ischemic events (eg, TIMI risk score <2 or =2) or at high risk of bleeding and who are already receiving aspirin and a P2Y12 receptor inhibitor, upstream GP IIb/IIIa inhibitors are not recommended.[31][32][33] (Level of Evidence: B)"
Class III: Harm
"1. In UA/NSTEMI patients with a prior history of stroke and/or TIA for whom PCI is planned, prasugrel* is potentially harmful as part of a dual antiplatelet therapy regimen.[30] (Level of Evidence: B)"
Class IIa
"1. For UA/NSTEMI patients in whom an initial conservative strategy is selected and who have recurrent ischemic discomfort with aspirin, a P2Y12 receptor inhibitor (clopidogrel or ticagrelor), and anticoagulant therapy, it is reasonable to add a GP IIb/IIIa inhibitor before diagnostic angiography. (Level of Evidence: C)"
"2. For UA/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.[34][35][36] (Level of Evidence: B)"
Class IIb
"1. For UA/NSTEMI patients in whom an initial conservative (ie, noninvasive) strategy is selected, it may be reasonable to add eptifibatide or tirofiban to anticoagulant and oral antiplatelet therapy.[19][20] (Level of Evidence: B)"
"2. Prasugrel* 60 mg may be considered for administration promptly upon presentation in patients with UA/NSTEMI for whom PCI is planned, before definition of coronary anatomy if both the risk for bleeding is low and the need for CABG is considered unlikely.[30][33] (Level of Evidence: C)"
"3. The use of upstream GP IIb/IIIa inhibitors may be considered in high-risk UA/NSTEMI patients already receiving aspirin and a P2Y12 receptor inhibitor (clopidogrel or ticagrelor) 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.[19][20][25][31][37] (Level of Evidence: B)"
"4. In patients with definite UA/NSTEMI undergoing PCI as part of an early invasive strategy, the use of a loading dose of clopidogrel of 600 mg, followed by a higher maintenance dose of 150 mg daily for 6 days, then 75 mg daily may be reasonable in patients not considered at high risk for bleeding.[27] (Level of Evidence: B)"

* Patients weighing <60 kg have an increased exposure to the active metabolite of prasugrel and an increased risk of bleeding on a 10-mg once– daily maintenance dose. Consideration should be given to lowering the maintenance dose to 5 mg in patients who weigh <60 kg, although the effectiveness and safety of the 5-mg dose have not been studied prospectively. For post-PCI patients receiving a BMS or DES, a daily maintenance dose should be given for at least 12 months and for up to 15 months unless the risk of bleeding outweighs the anticipated net benefit afforded by a thienopyridine. Do not use prasugrel in patients with active pathological bleeding or a history of TIA or stroke. In patients >75 years of age, prasugrel is generally not recommended because of the increased risk of fatal and intracranial bleeding and uncertain benefit except in high-risk situations (patients with diabetes or a history of prior MI), in which its effect appears to be greater and its use may be considered. Do not start prasugrel in patients likely to undergo urgent CABG. When possible, discontinue prasugrel at least 7 days before any surgery.35 Additional risk factors for bleeding include body weight <60 kg, propensity to bleed, and concomitant use of medications that increase the risk of bleeding (eg, warfarin, heparin, fibrinolytic therapy, or chronic use of nonsteroidal anti-inflammatory drugs).

** The recommended maintenance dose of aspirin to be used with ticagrelor is 81 mg daily. Ticagrelor's benefits were observed irrespective of prior therapy with clopidogrel. When possible, discontinue ticagrelor at least 5 days before any surgery. Issues of patient compliance may be especially important. Consideration should be given to the potential and as yet undetermined risk of intracranial hemorrhage in patients with prior stroke or TIA.

*** Applies to patients who were not treated chronically with these medications.

References

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