Section F: Clinical guidelines ACC/AHA guidelines for UA/NSTEMI: Class I recommendations for antithrombotic therapy Content Points: The American College of Cardiology (ACC)/American Heart Association (AHA) classification I refers to “Conditions for which there is evidence and/or general agreement that a given procedure or treatment is useful and effective.”1 As shown on the slide, ACC/AHA class I recommendations for antithrombotic therapy tailor the intensity of treatment to individual risk. An LMWH can be substituted for UFH in patients for whom ACS is likely or definite. However, the recommendations at present reserve UFH for patients undergoing intervention, although it is noted that data suggest that enoxaparin may provide more reproducible inhibition of platelet aggregation and less prolongation in bleeding time. Ongoing trials may provide further insight into the role of LMWH in patients for whom PCI is planned.

TIMI risk score: Suggested method for estimating early risk Content Points: Antman et al developed a risk score based on data from the TIMI 11B trial.46 The score has been validated in ESSENCE, TACTICS–TIMI 18, and PRISM-PLUS (Platelet Receptor Inhibition in Ischemic Syndrome Management in Patients Limited by Unstable Signs and Symptoms). Seven prognostic variables are listed on this slide. As the risk score increases from 0 to 7, patients will derive progressively greater benefit from LMWH, IV GP IIb/IIIa inhibition, and early PCI.19

ACC/AHA guidelines for UA/NSTEMI Content Points: Antiplatelet therapy is a cornerstone in the management of UA/NSTEMI. The ACC/AHA guidelines consider the following three classes of antiplatelet therapy to be useful: aspirin, thienopyridines, and IV GP IIb/IIIa inhibition. – Antiplatelet therapy with aspirin should be initiated promptly and continued indefinitely.1 This is a class I recommendation. Clopidogrel is the preferred thienopyridine over ticlopidine. – Clopidogrel should be administered to patients who are hypersensitive or have major gastrointestinal intolerance to aspirin (level of evidence: A, indicating that the data on which this recommendation is based are derived from multiple large-scale randomized trials) In patients for whom an early intervention strategy is planned, combined therapy of aspirin and clopidogrel should be initiated as soon as possible on admission and continued for at least 1 month (level of evidence: A). – Clopidogrel may be continued for up to 9 months (level of evidence: B, indicating that the data on which this recommendation is based were derived from a limited number of randomized trials that involved small numbers of patients, or from careful analysis of non-randomized trials or observational registries) In patients for whom PCI is planned, clopidogrel should be started and continued for at least 1 month (level of evidence: A) and up to 9 months in patients who are not at high risk for bleeding (level of evidence: B). However, clopidogrel should be withheld from patients 5 to 7 days before a planned coronary artery bypass procedure (level of evidence: B).

ACC/AHA guidelines for UA/NSTEMI: IV GP IIb/IIIa inhibition Content Points: The ACC/AHA recommendations reflect the large database of positive studies on IV GP IIb/IIIa inhibition in the setting of PCI. Class I recommendations are that GP IIb/IIIa inhibition, aspirin, and heparin should be administered to patients scheduled for catheterization and PCI.1 GP IIb/IIIa inhibition may also be administered just prior to PCI (level of evidence: A).

ACC/AHA guidelines for UA/NSTEMI: IV GP IIb/IIIa inhibition Content Points: Class IIa recommendations indicate conflicting evidence and/or divergence of opinion about the usefulness/efficacy of a treatment, although the weight of evidence is in favor of usefulness/efficacy.1 ACC/AHA class IIa recommendations for IV GP IIb/IIIa inhibition concern its use in patients already receiving clopidogrel and the specific roles of eptifibatide and tirofiban. Eptifibatide and tirofiban are the GP IIb/IIIa inhibitors of choice for patients in whom an invasive management strategy is not planned (level of evidence: A). In patients for whom catheterization and PCI are planned (and for whom clopidogrel is now recommended), GP IIb/IIIa inhibition may also be administered (level of evidence: B).

ACC/AHA guidelines for UA/NSTEMI: IV GP IIb/IIIa inhibition Content Points: Class IIb recommendations indicate conflicting evidence and/or divergence of opinion about the usefulness/efficacy of a treatment, with the usefulness/efficacy less well-established by evidence/opinion as for class IIa.1 Class IIb recommendations for eptifibatide and tirofiban are that they may be added to antiplatelet (aspirin plus clopidogrel) plus anticoagulant (heparins) therapy in patients without continuing ischemia and in whom PCI is not planned (level of evidence: B). That is, GP IIb/IIIa inhibition is of questionable benefit in patients who do not undergo PCI unless these patients have high-risk features.

ACC/AHA guidelines for UA/NSTEMI Content Points: Class III recommendations indicate that there is evidence and/or general agreement that the procedure/treatment is not useful/effective and in some cases may be harmful.1 Use of fibrinolytic therapy in patients with ACS is a class III indication, unless patients have ST-segment elevation, a true posterior MI, or presumed new left bundle-branch block (level of evidence: A). Based on GUSTO IV-ACS results, use of abciximab in patients for whom PCI is not planned is a class III indication.1,15

ACC/AHA guidelines for UA/NSTEMI: Heparins Content Points: The ACC/AHA guidelines provide the following class I recommendation regarding anticoagulation therapy with heparins: – Anticoagulation with subcutaneous LMWH or IV UFH should be added to antiplatelet therapy with aspirin and/or clopidogrel (level of evidence: A) – This is given an upgraded level of evidence from the previous (2000) guidelines Because of the number of studies that have appeared supporting the use of enoxaparin, the following class IIa recommendation is given: – Enoxaparin is preferable to UFH unless coronary artery bypass is planned within 24 hours, since the anticoagulant effect of UFH can be reversed more readily It is also noted that data are emerging to show that enoxaparin can be safely used as anticoagulant therapy in the setting of PCI.33,47 An alternative suggested approach is to use LMWH during the period of initial stabilization and to withhold the dose on the morning of the procedure.1 – If an intervention is required and more than 8 hours have elapsed since the last dose of LMWH, UFH can be used for the PCI

ACC/AHA guidelines for UA/NSTEMI Content Points: With advances in anticoagulation and antiplatelet therapies, and in stent design and implantation techniques, an early invasive strategy may provide advantages over medical management in many patients. The ACC/AHA provide guidelines for considering early invasive strategy.1 High-risk indicators are listed on the slide. In the absence of any of these indicators, either an early conservative or an early invasive strategy may be offered in hospitalized patients without contraindications for revascularization (level of evidence: B).