Table 3.

Recommendations for Additional Management of Antiplatelet and Anticoagulant Therapy

2007 Recommendations2011 Focused Update RecommendationsComments
Class I
    For UA/NSTEMI patients in whom an initial conservative strategy is selected and no subsequent features appear that would necessitate diagnostic angiography (recurrent symptoms/ischemia, HF, or serious arrhythmias), a stress test should be performed. (Level of Evidence: B) (Fig. 8; Box O)
  1. If, after stress testing, the patient is classified as not at low risk, diagnostic angiography should be performed. (Level of Evidence: A) (Fig. 8; Box E1)

  2. If, after stress testing, the patient is classified as being at low risk (Fig. 8; Box E2), the instructions noted below should be followed in preparation for discharge (Fig. 8; Box K) (Level of Evidence: A):

    1. Continue ASA indefinitely. (Level of Evidence: A)

    2. Continue clopidogrel for at least 1 month (Level of Evidence: A) and ideally up to 1 year. (Level of Evidence: B)

    3. Discontinue IV GP IIb/IIIa inhibitor if started previously. (Level of Evidence: A)

    4. Continue UFH for 48 hours or administer enoxaparin or fondaparinux for the duration of hospitalization, up to 8 days, and then discontinue anticoagulant therapy. (Level of Evidence: A)

1. For UA/NSTEMI patients in whom an initial conservative strategy is selected and no subsequent features appear that would necessitate diagnostic angiography (recurrent symptoms/ischemia, HF, or serious arrhythmias), a stress test should be performed.26 (Level of Evidence: B)
  1. If, after stress testing, the patient is classified as not at low risk, diagnostic angiography should be performed.25,26 (Level of Evidence: A)

  2. If, after stress testing, the patient is classified as being at low risk, the instructions noted below should be followed in preparation for discharge25,26:

    1. Continue ASA indefinitely.4,6,10 (Level of Evidence: A)

    2. Continue clopidogrel for at least 1 month13 and ideally up to 1 year.11,13 (Level of Evidence: B)

    3. Discontinue IV GP IIb/IIIa inhibitor if started previously.19,20 (Level of Evidence: A)

    4. Continue UFH for 48 hours8,39 (Level of Evidence: A) or administer enoxaparin4042 (Level of Evidence: A) or fondaparinux43 (Level of Evidence: B) for the duration of hospitalization, up to 8 days, and then discontinue anticoagulant therapy.

Modified recommendation (changed level of evidence from A to B for 1-month clopidogrel administration; clarified levels of evidence for UFH, enoxaparin, and fondaparinux).
    For UA/NSTEMI patients in whom CABG is selected as a postangiography management strategy, the instructions noted below should be followed (Fig. 9; Box G).
  1. Continue ASA. (Level of Evidence: A)

  2. Discontinue clopidogrel 5 to 7 days before elective CABG. (Level of Evidence: B) More urgent surgery, if necessary, may be performed by experienced surgeons if the incremental bleeding risk is considered acceptable. (Level of Evidence: C)

  3. Discontinue IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban) 4 hours before CABG. (Level of Evidence: B)

  4. Anticoagulant therapy should be managed as follows:

    1. Continue UFH. (Level of Evidence: B)

    2. Discontinue enoxaparin* 12 to 24 hours before CABG and dose with UFH per institutional practice. (Level of Evidence: B)

    3. Discontinue fondaparinux 24 hours before CABG and dose with UFH per institutional practice. (Level of Evidence: B)

    4. Discontinue bivalirudin 3 hours before CABG and dose with UFH per institutional practice. (Level of Evidence: B)

2. For UA/NSTEMI patients in whom CABG is selected as a postangiography management strategy, the instructions noted below should be followed.
  1. Continue ASA.4448 (Level of Evidence: A)

  2. See Class I, #3, in this section.

  3. Discontinue IV GP IIb/IIIa inhibitor (eptifibatide or tirofiban) 4 hours before CABG.4951 (Level of Evidence: B)

  4. Anticoagulant therapy should be managed as follows:

    1. Continue UFH.40,5254 (Level of Evidence: B)

    2. Discontinue enoxaparin 12 to 24 hours before CABG and dose with UFH per institutional practice.40,5254 (Level of Evidence: B)

    3. Discontinue fondaparinux 24 hours before CABG and dose with UFH per institutional practice.55,56 (Level of Evidence: B)

    4. Discontinue bivalirudin 3 hours before CABG and dose with UFH per institutional practice.57,58 (Level of Evidence: B)

Modified recommendation (changed item “b” to include prasugrel and be a stand-alone recommendation; see Class I, #3, in this section).
    For UA/NSTEMI patients in whom CABG is selected as a postangiography management strategy, the instructions noted below should be followed (Fig. 9; Box G). b. Discontinue clopidogrel 5 to 7 days before elective CABG. (Level of Evidence: B) More urgent surgery, if necessary, may be performed by experienced surgeons if the incremental bleeding risk is considered acceptable. (Level of Evidence: C)3. In patients taking a thienopyridine in whom CABG is planned and can be delayed, it is recommended that the drug be discontinued to allow for dissipation of the antiplatelet effect13 (Level of Evidence: B) The period of withdrawal should be at least 5 days in patients receiving clopidogrel13,18,59 (Level of Evidence: B) and at least 7 days in patients receiving prasugrel*35 (Level of Evidence: C) unless the need for revascularization and/or the net benefit of the thienopyridine outweighs the potential risks of excess bleeding.60 (Level of Evidence: C)Modified recommendation (changed to include prasugrel and update length of withdrawal period; from Class I, #2, in this section).
    For UA/NSTEMI patients in whom PCI has been selected as a postangiography management strategy, the instructions noted below should be followed (Fig. 9; Box H):
  1. Continue ASA. (Level of Evidence: A)

  2. Administer a loading dose of clopidogrel if not started before diagnostic angiography. (Level of Evidence: A)

  3. Administer an IV GP IIb/IIIa inhibitor (abciximab, eptifibatide, or tirofiban) if not started before diagnostic angiography for troponin-positive and other high-risk patients (Level of Evidence: A). See Class IIa recommendation below if bivalirudin was selected as the anticoagulant.

  4. Discontinue anticoagulant therapy after PCI for uncomplicated cases. (Level of Evidence: B)

4. For UA/NSTEMI patients in whom PCI has been selected as a postangiography management strategy, the instructions noted below should be followed:
  1. Continue ASA.4,6,10 (Level of Evidence: A)

  2. Administer a loading dose of a thienopyridine if not started before diagnostic angiography.12,29,31,61,62 (Level of Evidence: A)

  3. See Class IIa, #1, in this section.

  4. Discontinue anticoagulant therapy after PCI for uncomplicated cases.40,41,6365 (Level of Evidence: B)

Modified recommendation (included language to allow for prasugrel as choice of thienopyridine; class of item “c” changed from I to IIa).
    For UA/NSTEMI patients in whom medical therapy is selected as a management strategy and in whom no significant obstructive CAD on angiography was found, antiplatelet and anticoagulant therapy should be administered at the discretion of the clinician (Level of Evidence: C). For patients in whom evidence of coronary atherosclerosis is present (eg, luminal irregularities or intravascular ultrasound-demonstrated lesions), albeit without flow-limiting stenoses, long-term treatment with ASA and other secondary prevention measures should be prescribed. (Fig. 9; Box I) (Level of Evidence: C)5.    For UA/NSTEMI patients in whom medical therapy is selected as a management strategy and in whom no significant obstructive CAD on angiography was found, antiplatelet and anticoagulant therapy should be administered at the discretion of the clinician (Level of Evidence: C). For patients in whom evidence of coronary atherosclerosis is present (eg, luminal irregularities or intravascular ultrasound-demonstrated lesions), albeit without flow-limiting stenoses, long-term treatment with ASA and other secondary prevention measures should be prescribed. (Level of Evidence: C)2007 recommendation remains current.
    For UA/NSTEMI patients in whom medical therapy is selected as a management strategy and in whom CAD was found on angiography, the following approach is recommended (Fig. 9; Box J):
  1. Continue ASA. (Level of Evidence: A)

  2. Administer a loading dose of clopidogrel† if not given before diagnostic angiography. (Level of Evidence: A)

  3. Discontinue IV GP IIb/IIIa inhibitor if started previously. (Level of Evidence: B)

  4. Anticoagulant therapy should be managed as follows:

    1. Continue IV UFH for at least 48 hours or until discharge if given before diagnostic angiography. (Level of Evidence: A)

    2. Continue enoxaparin for duration of hospitalization, up to 8 days, if given before diagnostic angiography. (Level of Evidence: A)

    3. Continue fondaparinux for duration of hospitalization, up to 8 days, if given before diagnostic angiography. (Level of Evidence: B)

    4. Either discontinue bivalirudin or continue at a dose of 0.25 mg/kg per hour for up to 72 hours at the physician's discretion, if given before diagnostic angiography. (Level of Evidence: B)

6. For UA/NSTEMI patients in whom medical therapy is selected as a management strategy and in whom CAD was found on angiography, the following approach is recommended:
  1. Continue ASA.4,6,10 (Level of Evidence: A)

  2. Administer a loading dose of clopidogrel if not given before diagnostic angiography.13 (Level of Evidence: B)

  3. Discontinue IV GP IIb/IIIa inhibitor if started previously.16,19,20,38 (Level of Evidence: B)

  4. Anticoagulant therapy should be managed as follows:

    1. Continue IV UFH for at least 48 hours or until discharge if given before diagnostic angiography.8,39,40 (Level of Evidence: A)

    2. Continue enoxaparin for duration of hospitalization, up to 8 days, if given before diagnostic angiography.4042,56 (Level of Evidence: A)

    3. Continue fondaparinux for duration of hospitalization, up to 8 days, if given before diagnostic angiography.43 (Level of Evidence: B)

    4. Either discontinue bivalirudin or continue at a dose of 0.25 mg/kg per hour for up to 72 hours at the physician's discretion if given before diagnostic angiography.34,67,68 (Level of Evidence: B)

Modified recommendation (changed level of evidence from A to B for clopidogrel loading dose).
    For UA/NSTEMI patients in whom a conservative strategy is selected and who do not undergo angiography or stress testing, the instructions noted below should be followed (Fig. 8; Box K):
  1. Continue ASA indefinitely. (Level of Evidence: A)

  2. Continue clopidogrel for at least 1 month (Level of Evidence: A) and ideally up to 1 year. (Level of Evidence: B)

  3. Discontinue IV GP IIb/IIIa inhibitor if started previously. (Level of Evidence: A)

  4. Continue UFH for 48 hours or administer enoxaparin or fondaparinux for the duration of hospitalization, up to 8 days, and then discontinue anticoagulant therapy. (Level of Evidence: A)

7. For UA/NSTEMI patients in whom a conservative strategy is selected and who do not undergo angiography or stress testing, the instructions noted below should be followed:
  1. Continue ASA indefinitely.4,6,10 (Level of Evidence: A)

  2. Continue clopidogrel for at least 1 month13 and ideally up to 1 year.11,13,121 (Level of Evidence: B)

  3. Discontinue IV GP IIb/IIIa inhibitor if started previously.19,20 (Level of Evidence: A)

  4. Continue UFH for 48 hours8,39 (Level of Evidence: A) or administer enoxaparin4042 (Level of Evidence: A) or fondaparinux (Level of Evidence: B) for the duration of hospitalization, up to 8 days,43 and then discontinue anticoagulant therapy.

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 and in whom no subsequent features appear that would necessitate diagnostic angiography (recurrent symptoms/ischemia, HF, or serious arrhythmias), LVEF should be measured. (Level of Evidence: B) (Fig. 8; Box L)8. For UA/NSTEMI patients in whom an initial conservative strategy is selected and in whom no subsequent features appear that would necessitate diagnostic angiography (recurrent symptoms/ischemia, HF, or serious arrhythmias), LVEF should be measured.25,6972 (Level of Evidence: B)2007 recommendation remains current.
Class IIa
1. For UA/NSTEMI patients in whom PCI has been selected as a postangiography management strategy, it is reasonable to administer an IV GP IIb/IIIa inhibitor (abciximab, eptifibatide, or tirofiban) if not started before diagnostic angiography, particularly for troponin-positive and/or other high-risk patients.25,27 (Level of Evidence: A)Modified recommendation (see Class I, #4, in this section).
    For UA/NSTEMI patients in whom PCI is selected as a management strategy, it is reasonable to omit administration of an IV GP IIb/IIIa antagonist if bivalirudin was selected as the anticoagulant and at least 300 mg of clopidogrel was administered at least 6 hours earlier. (Level of Evidence: B) (Fig. 9)2. For UA/NSTEMI patients in whom PCI is selected as a management strategy, it is reasonable to omit administration of an IV GP IIb/IIIa inhibitor if bivalirudin was selected as the anticoagulant and at least 300 mg of clopidogrel was administered at least 6 hours earlier.16,25 (Level of Evidence: B)2007 recommendation remains current.
    If LVEF is ≤0.40, it is reasonable to perform diagnostic angiography. (Level of Evidence: B) (Fig. 8; Box M)3. If LVEF is ≤0.40, it is reasonable to perform diagnostic angiography.6972 (Level of Evidence: B)2007 recommendation remains current.
    If LVEF is greater than 0.40, it is reasonable to perform a stress test. (Level of Evidence: B) (Fig. 8; Box N)4. If LVEF is greater than 0.40, it is reasonable to perform a stress test.69 (Level of Evidence: B)2007 recommendation remains current.
Class IIb
    For UA/NSTEMI patients in whom PCI is selected as a management strategy, it may be reasonable to omit an IV GP IIb/IIIa inhibitor if not started before diagnostic angiography for troponin-negative patients without other clinical or angiographic high-risk features. (Level of Evidence: C)Deleted recommendation
1. Platelet function testing to determine platelet inhibitory response in patients with UA/NSTEMI (or, after ACS and PCI) on thienopyridine therapy may be considered if results of testing may alter management.7377 (Level of Evidence: B)New recommendation
2. Genotyping for a CYP2C19 loss of function variant in patients with UA/NSTEMI (or, after ACS and with PCI) on clopidogrel therapy might be considered if results of testing may alter management.7884 (Level of Evidence: C)New recommendation
Class III: No Benefit
    IV fibrinolytic therapy is not indicated in patients without acute ST-segment elevation, a true posterior MI, or a presumed new left bundle-branch block. (Level of Evidence: A)1. IV fibrinolytic therapy is not indicated in patients without acute ST-segment elevation, a true posterior MI, or a presumed new left bundle-branch block.85 (Level of Evidence: A)2007 recommendation remains current.
  • * 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 bare-metal stent (BMS) or drug-eluting stent (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