Dosing Table for Antiplatelet and Anticoagulant Therapy Discussed in This Focused Update to Support PCI in NSTEMI
| Drug* | During PCI | Comments ▶All Patients to Receive ASA (162–325 mg) | |
|---|---|---|---|
| Patient Received Initial Medical Treatment (With a Thienopyridine) | Patient Did Not Receive Initial Medical Treatment (With a Thienopyridine) | ||
| GP IIb/IIIa receptor antagonists | |||
| Abciximab | Of uncertain benefit | LD of 0.25 mg/kg IV bolus MD of 0.125 mcg/kg per min (maximum 10 mcg/min) (Class I, LOE: A) | ▶Continue for up to 12 h at the discretion of the physician.198,199 |
| Eptifibatide | Of uncertain benefit | LD of 180 mcg/kg IV bolus followed 10 min later by second IV bolus of 180 mcg/kg MD of 2.0 mcg/kg per min, started after first bolus; reduce infusion by 50% in patients with estimated creatinine clearance <50 mL/min (Class I, LOE: A) | ▶An LD of eptifibatide is FDA approved when the medication is initiated in UA/NSTEMI patients who are started on medical therapy and when there is an appreciable delay to angiography/PCI: LD of 180 mcg/kg IV bolus followed by MD of 2.0 mcg/kg per min started after bolus; reduce infusion by 50% in patients with estimated creatinine clearance <50 mL/min (Class I, LOE:B). ▶Infusion should be continued for 12 to 18 h at the discretion of the physician.198 |
| Tirofiban | Of uncertain benefit | LD of 25 mcg/kg IV bolus MD of IV infusion of 0.15 mcg/kg per min; reduce rate of infusion by 50% in patients with estimated creatinine clearance <30 mL/min (Class I, LOE: B) | ▶Increased dosing over previous recommendation.199,202 ▶Continue for up to 18 h at the discretion of the physician.202 ▶A lower-dose regimen for tirofiban is FDA approved and has been shown to be effective when used to treat UA/NSTEMI patients who are started on medical therapy and when there is a substantial delay to angiography/PCI (eg, 48 h):LD of 50 mcg/mL administered at an initial rate of 0.4 mcg/kg per min for 30 min MD of a continuous infusion of 0.1 mcg/kg per min. Continue the infusion through angiography and for 12 to 24 h after angioplasty or atherectomy.19 |
| Thienopyridines | |||
| Clopidogrel† | If 600 mg given orally, then no additional treatment. A second LD of 300 mg may be given orally to supplement a prior LD of 300 mg (Class I, LOE: C) | LD of 300–600 mg orally (Class I, LOE: A) MD of 75 mg orally per d (Class I, LOE: A) An MD of 150 mg orally per d for initial 6 d may be considered (Class IIb, LOE: B) | ▶Optimum LD requires clinical consideration. ▶Dose for patients >75 y of age has not been established. ▶There is a recommended duration of therapy for all post-PCI patients receiving a BMS or DES. ▶Period of withdrawal before surgery should be at least 5 d.(For full explanations, see footnote.) |
| Prasugrel‡ | No data are available to guide decision making | LD of 60 mg orally MD of 10 mg orally per d (Class I, LOE: B) | ▶There are no data for treatment with prasugrel before PCI. ▶MD of 5 mg orally per d in special circumstances. ▶Special dosing for patients <60 kg. ▶There is a recommended duration of therapy for all post-PCI patients receiving a DES. ▶Prasugrel is generally not recommended for patients ≥75 y of age because of increased bleeding risk and uncertain benefit compared with clopidogrel. ▶Contraindicated for use in patients with prior history of TIA or stroke. (For full explanations, see footnote.) |
| Parenteral anticoagulants | |||
| Bivalirudin | For patients who have received UFH, wait 30 min, then give 0.75 mg/kg bolus, then 1.75 mg/kg per h infusion (Class I, LOE: B) | 0.75 mg/kg bolus, 1.75 mg/kg per h infusion | ▶Bivalirudin may be used to support PCI and UA/NSTEMI with or without previously administered UFH with the addition of 600 mg of clopidogrel.198 ▶In UA/NSTEMI patients undergoing PCI who are at high risk of bleeding, bivalirudin anticoagulation is reasonable.198 |
| UFH | IV GP IIb/IIIa planned: target ACT 200–250 s No IV GP IIb/IIIa planned: target ACT 250–300 s for HemoTec, 300–350 s for Hemochron (Class I, LOE: B) | IV GP IIb/IIIa planned: 50–70 units/kg bolus to achieve an ACT of 200–250 s. No IV GP IIb/IIIa planned: 70–100 units/kg bolus to achieve target ACT of 250–300 s for HemoTec, 300–350 s for Hemochron (Class I, LOE:B) | |
* This list is in alphabetical order and is not meant to indicate a particular therapy preference. This drug table does not make recommendations for combinations of listed drugs. It is only meant to indicate an approved or recommended dosage if a drug is chosen for a given situation.
† The optimum LD of clopidogrel has not been established. Randomized trials establishing its efficacy and providing data on bleeding risks used an LD of 300 mg orally followed by a daily oral dose of 75 mg.22,203 Higher oral LDs such as 600 mg or >900 mg204 of clopidogrel more rapidly inhibit platelet aggregation and achieve a higher absolute level of inhibition of platelet aggregation, but the additive clinical efficacy and safety of higher oral LD have not been rigorously established. For post-PCI patients receiving a DES, a daily MD should be given for at least 12 mo unless the risk of bleeding outweighs the anticipated net benefit afforded by a thienopyridine. For post-PCI patients receiving a BMS, an MD should be given for a minimum of 1 mo98 and ideally up to 12 mo (unless the risk of bleeding outweighs the anticipated net benefit afforded by a thienopyridine; then it should be given for a minimum of 2 wks). The necessity for giving an LD of clopidogrel before PCI is driven by the pharmacokinetics of clopidogrel, for which a period of several hours is required to achieve desired levels of platelet inhibition. Patients who have a reduced-function CYP2C19 allele have significantly lower levels of the active metabolite of clopidogrel, diminished platelet inhibition, and a higher rate of MACE, including stent thrombosis.81 In NSTEMI patients taking clopidogrel for whom CABG is planned and can be delayed, it is reasonable to discontinue the clopidogrel to allow for dissipation of the antiplatelet effect unless the urgency for revascularization and/or the net benefit of clopidogrel outweigh the potential risks of excess bleeding. The period of withdrawal should be at least 5 d in patients receiving clopidogrel.59
‡ 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 mo and for up to 15 mo 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 y 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 d 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
ACT indicates activated clotting time; ASA, aspirin; BMS, bare-metal stent; CABG, coronary artery bypass graft; DES, drug-eluting stent; FDA, Food and Drug Administration; GP, glycoprotein; IV, intravenous; LD, loading dose; LOE, level of evidence; MACE, major adverse cardiac events; MD, maintenance dose; MI, myocardial infarction; NSTEMI, non–ST-elevation myocardial infarction; PCI, percutaneous coronary intervention; PPI, proton pump inhibitor; STEMI, ST-elevation myocardial infarction; TIA, transient ischemic attack; UA/NSTEMI, unstable angina/non–ST-elevation myocardial infarction; and UFH, unfractionated heparin.