Unstable angina NSTEMI Antiplatelet therapy recommendations

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Arzu Kalayci, M.D. [2]

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.

2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease (Updating the 2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes (DO NOT EDIT))

Recommendations for Duration of DAPT in Patients With ACS Treated With Medical Therapy Alone[1]

Class I
"1.In patients with ACS who are managed with medical therapy alone (without revascularization or fibrinolytic therapy) and treated with DAPT, P2Y12 inhibitor therapy (clopidogrel or ticagrelor) should be continued for at least 12 monthsLevel of Evidence: B-R)"
"2.In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 100 mg) is recommended(Level of Evidence: B-NR)"
Class IIa
"1.In patients with NSTE–ACS who are managed with medical therapy alone (without revascularization or fibrinolytic therapy) and treated with DAPT, it is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy(Level of Evidence: B-R)"
Class IIb
"1.In patients with ACS treated with medical therapy alone (without revascularization or fibrinolytic therapy) who have

tolerated DAPT without bleeding complication and who are not at high bleeding risk (e.g., prior bleeding on DAPT, coagulopathy, oral anticoagulant use), continuation of DAPT for longer than 12 months may be reasonable(Level of Evidence: A SR)"

Initial Oral and Intravenous Antiplatelet Therapy in Patients With Definite or Likely NSTEACS Treated With an Initial Invasive or Ischemia-Guided Strategy

Class I
"1. Non–enteric-coated, chewable aspirin (162 mg to 325 mg) should be given to all patients with NSTE-ACS without contraindications as soon as possible after presentation, and a maintenance dose of aspirin (81 mg/d to 162 mg/d) should be continued indefinitely. (Level of Evidence: A)"
"2. In patients with NSTE-ACS who are unable to take aspirin because of hypersensitivity or major gastrointestinal intolerance, a loading dose of clopidogrel followed by a daily maintenance dose should be administered. (Level of Evidence: B)"
"3. A P2Y12 inhibitor (either clopidogrel or ticagrelor) in addition to aspirin should be administered for up to 12 months to all patients with NSTE-ACS without contraindications who are treated with either an early invasive§ or ischemia-guided strategy. Options include:
Class IIa
"1. It is reasonable to use ticagrelor in preference to clopidogrel for P2Y12 treatment in patients with NSTE-ACS who undergo an early invasive or ischemia-guided strategy. (Level of Evidence: B)"
Class IIb
"1. In patients with NSTE-ACS treated with an early invasive strategy and dual antiplatelet therapy (DAPT) with intermediate/high-risk features (e.g., positive troponin), a GP IIb/IIIa inhibitor may be considered as part of initial antiplatelet therapy. Preferred options are eptifibatide or tirofiban. (Level of Evidence: B)"

PCI—Antiplatelet and Anticoagulant Therapy

Oral and Intravenous Antiplatelet Agents

Class I
"1. Patients already taking daily aspirin before PCI should take 81 mg to 325 mg non–enteric-coated aspirin before PCI. (Level of Evidence: B)"
"2. Patients not on aspirin therapy should be given non–enteric-coated aspirin 325 mg as soon as possible before PCI. (Level of Evidence: B)"
"3. After PCI, aspirin should be continued indefinitely at a dose of 81 mg to 325 mg daily. (Level of Evidence: B)"
"4. A loading dose of a P2Y12 receptor inhibitor should be given before the procedure in patients undergoing PCI with stenting. (Level of Evidence: A) Options include:

a. Clopidogrel: 600 mg (Level of Evidence: B) or
b. Prasugrel: 60 mg (Level of Evidence: B) or
c. Ticagrelor: 180 mg (Level of Evidence: B)"

"5. In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) not adequately pretreated with clopidogrel or ticagrelor, it is useful to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-dose bolus tirofiban) at the time of PCI. (Level of Evidence: A)"
"6. In patients receiving a stent (bare-metal stent or drug-eluting stent [DES]) during PCI for NSTEACS,

P2Y12 inhibitor therapy should be given for at least 12 months. Options include:
a. Clopidogrel: 75 mg daily (Level of Evidence: B) or
b. Prasugrel: 10 mg daily (Level of Evidence: B) or
c. Ticagrelor: 90 mg twice daily (Level of Evidence: B)"

Class III (No Benefit)
"1. Prasugrel should not be administered to patients with a prior history of stroke or transient ischemic attack. (Level of Evidence: B-R)"
Class IIa
"1. It is reasonable to choose ticagrelor over clopidogrel for P2Y12 inhibition treatment in patients with NSTE-ACS treated with an early invasive strategy and/or coronary stenting. (Level of Evidence: B)"
"2. It is reasonable to choose prasugrel over clopidogrel for P2Y12 treatment in patients with NSTEACS who undergo PCI who are not at high risk of bleeding complications. (Level of Evidence: B)"
"3. In patients with NSTE-ACS and high-risk features (e.g., elevated troponin) treated with UFH and adequately pretreated with clopidogrel, it is reasonable to administer a GP IIb/IIIa inhibitor (abciximab, double-bolus eptifibatide, or high-bolus dose tirofiban) at the time of PCI. (Level of Evidence: B)"
"4. After PCI, it is reasonable to use 81 mg per day of aspirin in preference to higher maintenance doses. (Level of Evidence: B)"
"5. If the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of P2Y12 inhibitor therapy after stent implantation, earlier discontinuation (e.g., <12 months) of P2Y12 inhibitor therapy is reasonable. (Level of Evidence: C)"
"6. In patients with ACS (NSTE-ACS or STEMI) treated with DAPT after coronary stent implantation and in patients with NSTE-ACS treated with medical therapy alone (without revascularization), it is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy (Level of Evidence: B-R)"
"7. In patients with ACS (NSTE-ACS or STEMI) treated with DAPT after coronary stent implantation who are not at high risk for bleeding complications and who do not have a history of stroke or TIA, it is reasonable to choose prasugrel over clopidogrel for maintenance P2Y12 inhibitor therapy (Level of Evidence: B-R)"

Recommendation for aspirin dosing in patients treated with DAPT

Class I
"1. In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 100 mg) is recommended(Level of Evidence: B-NR)"

Recommendations for duration of DAPT in patients with ACS treated with PCI

Class I
"1. In patients with ACS (NSTE-ACS or STEMI) treated with DAPT after BMS or DES implantation, P2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor) should be given for at least 12 months(Level of Evidence: B-R)"
"2. In patients treated with DAPT, a daily aspirin dose of 81 mg (range, 75 mg to 100 mg) is recommended(Level of Evidence: B-NR)"
Class IIa
"1. In patients with ACS (NSTE-ACS or STEMI) treated with DAPT after coronary stent implantation, it is reasonable to use ticagrelor in preference to clopidogrel for maintenance P2Y12 inhibitor therapy ( (Level of Evidence: B-R)"
"2. In patients with ACS (NSTE-ACS or STEMI) treated with DAPT after coronary stent implantation who are not at high risk for bleeding complications and who do not have a history of stroke or TIA, it is reasonable to choose prasugrel

over clopidogrel for maintenance P2Y12 inhibitor therapy (Level of Evidence: B-R)"

Class IIb
"1. In patients with ACS (NSTE-ACS or STEMI) treated with coronary stent implantation who have tolerated DAPT without a bleeding complication and who are not at high bleeding risk (e.g., prior bleeding on DAPT, coagulopathy,

oral anticoagulant use), continuation of DAPT (clopidogrel, prasugrel, or ticagrelor) for longer than 12 months may be reasonable (Level of Evidence: A)"

"2. In patients with ACS treated with DAPT after DES implantation who develop a high risk of bleeding (e.g., treatment with oral anticoagulant therapy), are at high risk of severe bleeding complication (e.g., major intracranial surgery),

or develop significant overt bleeding, discontinuation of P2Y12 inhibitor therapy after 6 months may be reasonable (Level of Evidence: C-LD)"

Class III (Harm)
"1. Prasugrel should not be administered to patients with a prior history of stroke or TIA (Level of Evidence: B-R)"

Medical Regimen and Use of Medications at Discharge

Combined Oral Anticoagulant Therapy and Antiplatelet Therapy in Patients With NSTEACS

Class I
"1. The duration of triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor in patients with NSTE-ACS should be minimized to the extent possible to limit the risk of bleeding. (Level of Evidence: C)"
"2. Proton pump inhibitors should be prescribed in patients with NSTE-ACS with a history of gastrointestinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor. (Level of Evidence: C)"
Class IIa
"1. Proton pump inhibitor use is reasonable in patients with NSTE-ACS without a known history of gastrointestinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor. (Level of Evidence: C)"
Class IIb
"1. Targeting oral anticoagulant therapy to a lower international normalized ratio (INR) (e.g., 2.0 to 2.5) may be reasonable in patients with NSTE-ACS managed with aspirin and a P2Y12 inhibitor. (Level of Evidence: C)"

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)[2]

Antiplatelet therapy (DO NOT EDIT)[2]

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.[3][4][5][6][7] (Level of Evidence: A)"
"2. A loading dose followed by daily maintenance dose of either clopidogrel[8][9][10] (Level of Evidence: C), prasugrel* (in PCI-treated patients)[11] (Level of Evidence: C), or ticagrelor**[12] (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.[8][13][14][15] (Level of Evidence: A) Aspirin should be initiated on presentation.[3][16][17][5][6][7][18] (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.[19][25][8] (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.[26][27] (Level of Evidence: A) Either an IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban[24][20][21] Level of Evidence: A), clopidogrel (loading dose followed by daily maintenance dose[8] Level of Evidence: B), or ticagrelor** (loading dose followed by daily maintenance dose[19] 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[28][29][30] (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.[31] (Level of Evidence: B)

c) Ticagrelor** 180 mg should be given as early as possible before or at the time of PCI.[19] (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[8][13], prasugrel* 10 mg daily[31], or ticagrelor** 90 mg twice daily[19] 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.[24][23] (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.[32][33][34] (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.[31] (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.[35][36][37] (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.[20][21] (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.[31][34] (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.[20][21][26][32][38] (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.[28] (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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References