Table 2.

Recommendations for Early Hospital Care Antiplatelet Therapy

2007 Recommendations2011 Focused Update RecommendationsComments
Class I
                ASA should be administered to UA/NSTEMI patients as soon as possible after hospital presentation and continued indefinitely in patients not known to be intolerant of that medication. (Level of Evidence: A) (Figs. 7 and 8; Box A)1. ASA should be administered to UA/NSTEMI patients as soon as possible after hospital presentation and continued indefinitely in patients who tolerate it.3–10* (Level of Evidence: A)Modified recommendation (changed wording for clarity).
                Clopidogrel (loading dose followed by daily maintenance dose) should be administered to UA/NSTEMI patients who are unable to take ASA because of hypersensitivity or major gastrointestinal intolerance. (Level of Evidence: A) (Figs. 7 and 8; Box A)2. Clopidogrel (loading dose followed by daily maintenance dose) should be administered to UA/NSTEMI patients who are unable to take ASA because of hypersensitivity or major gastrointestinal intolerance.11–13 (Level of Evidence: B)Modified recommendation (level of evidence changed from A to B because trials do not address the specific subgroups in this recommendation).
    In UA/NSTEMI patients with a history of gastrointestinal bleeding, when ASA and clopidogrel are administered alone or in combination, drugs to minimize the risk of recurrent gastrointestinal bleeding (eg, PPI), should be prescribed concomitantly. (Level of Evidence: B)Deleted recommendation (see ACCF/ACG/AHA PPI expert consensus document14).
    For UA/NSTEMI patients in whom an initial invasive strategy is selected, antiplatelet therapy in addition to ASA should be initiated before diagnostic angiography (upstream) with either clopidogrel (loading dose followed by daily maintenance dose) or an IV 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. 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.13,15–17 (Level of Evidence: A) ASA should be initiated on presentation.3–8,10 (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:

  • Clopidogrel13,17 (Level of Evidence: B); or

  • An IV GP IIb/IIIa inhibitor.18–21 (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 PCI13,17 (Level of Evidence: A); or

  • Prasugrel†22 (Level of Evidence: B); or

  • An IV GP IIb/IIIa inhibitor.18,21,23,24 (Level of Evidence: A)

Modified recommendation (modified to include prasugrel and define therapy more clearly).
    For UA/NSTEMI patients in whom an initial conservative (ie, noninvasive) strategy is selected (see Section 3.3), clopidogrel (loading dose followed by daily maintenance dose) should be added to ASA and anticoagulant therapy as soon as possible after admission and administered for at least 1 month (Level of Evidence: A) and ideally up to 1 year. (Level of Evidence: B) (Fig. 8; Box C2)4. For UA/NSTEMI patients in whom an initial conservative (ie, noninvasive) strategy is selected (see Section 3.3), clopidogrel (loading dose followed by daily maintenance dose) should be added to ASA and anticoagulant therapy as soon as possible after admission and administered for at least 1 month13 and ideally up to 1 year.11,13 (Level of Evidence: B)Modified recommendation (changed level of evidence from A to B for 1-month clopidogrel administration).
    For UA/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) (Fig. 8; Box D) 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: A) should be added to ASA and anticoagulant therapy before diagnostic angiography (upstream). (Level of Evidence: C)5. For UA/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.13,25,26 (Level of Evidence: A). Either an IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban19–21 [Level of Evidence: A]) or clopidogrel (loading dose followed by daily maintenance dose13,15 [Level of Evidence: B]) should be added to ASA and anticoagulant therapy before diagnostic angiography (upstream). (Level of Evidence: C)Modified recommendation (changed level of evidence from A to B for clopidogrel addition).
6.    A loading dose of thienopyridine is recommended for UA/NSTEMI patients for whom PCI is planned. Regimens should be 1 of the following:

  1. Clopidogrel 300 to 600 mg should be given as early as possible before or at the time of PCI13,27–31 (Level of Evidence: A) or

  2. 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.22 (Level of Evidence: B)

New recommendation (included to be concordant with 2009 STEMI and PCI Focused Update,32 modified for the UA/NSTEMI patient group).
7. The duration and maintenance dose of thienopyridine therapy should be as follows:

  1. In UA/NSTEMI patients undergoing PCI, clopidogrel 75 mg daily17 or prasugrel† 10 mg daily22 should be given for at least 12 months.13,17 (Level of Evidence: B)

  2. 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)

New recommendation (included to be concordant with 2009 STEMI and PCI Focused Update32).
Class IIa
    For UA/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)1. For UA/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 inhibitor before diagnostic angiography. (Level of Evidence: C)2007 recommendation remains current.
    For UA/NSTEMI patients in whom an initial invasive strategy is selected, it is reasonable to omit upstream administration of an IV GP IIb/IIIa antagonist before diagnostic angiography 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)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.16,33,34 (Level of Evidence: B)Modified recommendation (removed language about diagnostic angiography).
Class IIb
    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. (Level of Evidence: B) (Fig. 8; Box C2)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)2007 recommendation remains current.
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.22,35,36 (Level of Evidence: C)New recommendation
3. The use of upstream GP IIb/IIIa inhibitors may be considered in high-risk UA/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.19,20,25,27,37 (Level of Evidence: B)New recommendation
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)New recommendation
Class III: No Benefit
    Abciximab should not be administered to patients in whom PCI is not planned. (Level of Evidence: A)1. Abciximab should not be administered to patients in whom PCI is not planned.21,23 (Level of Evidence: A)2007 recommendation remains current.
2. In UA/NSTEMI patients who are at low risk for ischemic events (eg, 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.25,36–38 (Level of Evidence: B)New recommendation
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.22 (Level of Evidence: B)New recommendation (included to be concordant with 2009 STEMI and PCI Focused Update32).

  • * Refer to the ACC/AHA/SCAI Guideline for Percutaneous Coronary Intervention for long-term dosing of ASA following stent placement.

  • † 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).35