The correct answer is: C. Enoxaparin 1 mg/kg SC every 12 hours, continued for the duration of hospitalization or until PCI is performed.

Two initial treatment strategies are available for patients hospitalized with non–ST-elevation acute coronary syndromes (NSTE-ACS): the invasive strategy which triages patients to an invasive coronary angiography (either early or delayed) vs. the initial ischemia-guided strategy. The latter is more conservative at first and aims to identify those patients at higher risk (clinically, electrocardiographically, or via non-invasive tests for ischemia) who should undergo coronary angiography. The presence of diabetes, an elevated troponin, and ST changes on her electrocardiogram place this patient at high risk for recurrent myocardial infarction (MI) and death; therefore ,triage to the invasive strategy is appropriate. Regardless of the initial treatment strategy, all patients with definite NSTE-ACS (in the absence of absolute contraindications to antithrombotic therapy) should receive upon admission optimal oral antiplatelets, as well as parenteral anticoagulation.¹ The latter is given in order to inhibit thrombin activity. The combination of the two is more effective than either treatment alone.² Answer option A is, therefore, incorrect.

Several parenteral anticoagulants, which act differently on the coagulation cascade, have been studied in NSTE-ACS and are available for clinical use:

• Unfractionated heparin (UFH) is an indirect thrombin inhibitor that has a narrow therapeutic window that requires frequent aPTT monitoring. It is poorly absorbed by the subcutaneous route and, therefore, in the setting of NSTE-ACS, is given intravenously. The combination of UFH plus aspirin vs. aspirin alone in NSTE-ACS was shown to reduce ischemic events at the cost of an increased risk of bleeding.² Furthermore, this was demonstrated prior to the use of dual antiplatelet therapy and the early revascularization era. In the setting of NSTE-ACS, UFH should be administered for 48 hours or until PCI is performed (COR I, LOE B). Answer option B is not the best option because the timing of PCI may be delayed beyond 48 hours in this case. In addition, metanalyses of trials comparing low molecular weight heparins (LMWH; e.g., enoxaparin) to UFH demonstrated no significant differences between the two compounds for death at 30 days.^3,4 However, a significant reduction of the composite endpoint of death or MI at 30 days was observed in favor of enoxaparin vs. UFH treatment. No difference was found in major bleeding or blood transfusions at seven days after randomization. Furthermore, heparin-induced thrombocytopenia occurs in up to 15% of patients treated with UFH and is less frequent under LMWH. Given the better efficacy and similar safety profile of enoxaparin vs. UFH, it is also recommended by current guidelines (COR I, LOE A). ¹            
• Fondaparinux is an activated factor X inhibitor. In the OASIS-5 trial, SC fondaparinux was non-inferior to enoxaparin in terms of composite ischemic endpoints.⁵ However, fewer major bleeding events and more catheter-related thrombosis events during PCI were observed in the fondaparinux group. In patients treated initially with fondaparinux, UFH should be added during PCI in order to prevent catheter-related thrombosis. Based on current guidelines, fondaparinux should be continued during hospitalization or until PCI is performed (COR I, LOE B). Answer option D is not optimal because the duration of use of fondaparinux depends on the treatment strategy and use of PCI. 
• Bivalirudin is a direct thrombin inhibitor. In 13,819 patients with NSTE-ACS who were planned for an invasive strategy in the ACUITY trial, bivalirudin alone or with provisional glycoprotein (GP) IIb/IIIa receptor inhibitors showed similiar efficacy to heparin/LMWH plus GP IIbIIIa receptor inhibitors in reducing ischemic events, while significantly lowering major bleeding complications.⁶ However, the Acute Catheterization and Urgent Intervention Triage strategY (ACUITY) trial only included moderate-to-high-risk NSTE-ACS patients who were planned for invasive treatment. Therefore, current guidelines recommend initially using bivalirudin only in NSTE-ACS patients that are triaged to the early invasive strategy (COR I, LOE B). Since the treatment strategy for the patient above has not yet been determined, answer option E is not preferred.

In summary, several parenteral anticoagulants are approved for the treatment of a patient admitted with NSTE-ACS. Each has its own merits and drawbacks. These antithrombotic treatment recommendations are based mostly on randomized trials performed prior to the use of the more potent oral anti-platelets (e.g., ticagrelor, prasugrel) or use of contemporary PCI techniques. Thus, it is not clear whether their comparative efficacy, and not less important their comparative safety profile, implies to current practice. In general, all parenteral anticoagulation administered to a patient hospitalized with NSTE-ACS should be discontinued after coronary angiography is performed, unless otherwise indicated. The use of GP IIb/IIIa receptor inhibitors is beyond the scope of this paper, yet in brief, these agents may be administered nowadays during high risk PCI. There is no role for fibrinolytic therapy in patients with NSTE-ACS. Finally, it is prudent and essential for each clinician who admits a patient with NSTE-ACS to choose the most appropriate anticoagulant treatment, based on individual clinical and laboratory characteristics, while taking into account the patient’s ischemic and bleeding risks.

References

1. Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non–ST-elevation acute coronary syndromes: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2014 Sep 23. [Epub ahead of print]
2. Eikelboom JW, Anand SS, Malmberg K, et al. Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis. Lancet 2000;355:1936-42.
3. Petersen JL, Mahaffey KW, Hasselblad V, et al. Efficacy and bleeding complications among patients randomized to enoxaparin or unfractionated heparin for antithrombin therapy in non-ST-Segment elevation acute coronary syndromes: a systematic overview. JAMA 2004;292:89-96.
4. Murphy S, Gibson C, Morrow D, et al. Efficacy and safety of the low-molecular weight heparin enoxaparin compared with unfractionated heparin across the acute coronary syndrome spectrum: a meta-analysis. Eur Heart J 2007;28:2077–86.
5. Yusuf S, Mehta SR, Chrolavicius S, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 2006;354:1464-76.
6. Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006;355:2203-16.