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CLINICAL STATEMENTS AND GUIDELINES April 1, 2025 Circulation. 2025;151:e771–e862. DOI: 10.1161/CIR.0000000000001309 e794 ACS diagnosis for medical stabilization prior to planned angiography and PCI. In the EARLY-ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients with Non–ST-segment Elevation Acute Coronary Syndrome) trial, 9406 patients with NSTE-ACS were randomized to routine upstream use of eptifibatide (within 8 hours after presentation to the hospital) versus ad hoc adjunctive use at the time of PCI among patients with NSTE-ACS.4 Ischemic outcomes were not improved and bleeding was increased in the routine upstream eptifibatide arm. An alternative approach is routine adjunctive use of a glycoprotein IIb/IIIa inhibitor at the time of PCI for patients with STEMI or NSTE-ACS. Although early trials performed prior to use of potent P2Y12 inhibitors suggested that this approach improved procedural outcomes and reduced periprocedural myocardial necrosis, studies performed among patients receiving pretreatment with clopidogrel have not confirmed reduction of ischemic events with routine adjunctive glycoprotein IIb/IIIa inhibition and have increased bleeding complications.5,11 4.4 Parenteral Anticoagulation Recommendations for Parenteral Anticoagulation Referenced studies that support recommendations are summarized in the Evidence Table. COR LOE Recommendations NSTE-ACS: Upstream* Anticoagulant Therapy 1 B-R 1 In patients with NSTE-ACS, intravenous unfractionated heparin (UFH) is useful to reduce ischemic events.†1–4 1 B-R 2 In patients with NSTE-ACS in whom an early invasive approach is not anticipated, either enoxaparin or fondaparinux are recommended alternatives to UFH to reduce ischemic events.5–11 Anticoagulant Therapy in Patients Undergoing Coronary Revascularization 1 C-LD 3 In patients with ACS undergoing coronary revascularization (CABG or PCI) in the same admission, parenteral anticoagulation should be continued until revascularization to reduce ischemic events.12,13 Anticoagulant Therapy to Support PCI in ACS (STEMI and NSTE-ACS) 1 C-EO 4. In patients with ACS undergoing PCI, intravenous UFH is useful to reduce ischemic events.† 1 B-R 5 In patients with STEMI undergoing PCI, bivalirudin is useful as an alternative to UFH to reduce mortality and bleeding.†14–19 2b B-R 6. In patients with NSTE-ACS undergoing PCI, bivalirudin may be reasonable as an alternative to UFH to reduce bleeding.†16,20–23 2b B-R 7 In patients with ACS, intravenous enoxaparin may be considered as an alternative to UFH at the time of PCI to reduce ischemic events.‡7,8,24–26 3: Harm B-R 8 In patients with ACS, fondaparinux should not be used to support PCI because of the risk of catheter thrombosis.5,27 STEMI: Anticoagulant Therapy Treated With Fibrinolytic Therapy 1 A 9 In patients with STEMI treated with fibrinolytic therapy, parenteral anticoagulation should be continued for the duration of the hospital stay (maximum of 8 days) or until revascularization is performed to reduce ischemic events.9,10,27–29 1 A 10 In patients with STEMI treated with fibrinolytic therapy who are not intended to undergo an invasive approach, enoxaparin is the recommended anticoagulant to reduce ischemic events.9,10,28,29 1 B-R 11 In patients with STEMI treated with fibrinolytic therapy who are not intended to undergo an invasive approach, fondaparinux is a recommended alternative to reduce ischemic events.27,30 *At the time of diagnosis and prior to invasive coronary angiography if planned. †Adapted or ‡modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization.”31 Synopsis Parenteral anticoagulation is recommended for all patients with ACS, irrespective of the initial treatment strategy, to treat the underlying pathophysiologic process (coronary atherothrombosis) and reduce the risk of recurrent MACE (Table 10). Although eventual diagnostic reclassification can occur (ie, to other nonatherothrombotic ACS diagnoses such as coronary spasm or other conditions that can mimic ACS, such as stress cardiomyopathy or myocarditis), initial parenteral anticoagulation is intended to treat thrombus caused by atherosclerotic plaque disruption (rupture or erosion) in patients with presumed type 1 MI.32 Anticoagulation strategies are to be initiated upstream (at the time of diagnosis and prior to coronary angiography) and to support PCI or other reperfusion therapy. In patients with ACS undergoing PCI, intraprocedural thrombin generation and platelet aggregation may occur, for which reason parenteral anticoagulation is recommended to reduce the risk for thrombotic complications.33 The choice of a parenteral anticoagulant can be complex because it is influenced by various factors, including vascular access site, renal function, and concomitant use of other antiplatelet or anticoagulant agents. Heparin-induced thrombocytopenia can occur with both UFH and low-molecular-weight heparin; in this context, argatroban and bivalirudin are direct thrombin inhibitors that are acceptable alternative anticoagulants for patients with known heparin-induced thrombocytopenia.34,35 Recommendation-Specific Supportive Text 1 UFH has traditionally been the preferred anti- coagulant to treat patients with NSTE-ACS.1–4 However, limitations to its use include the lack of Recommendations for Parenteral Anticoagulation (Continued ) COR LOE Recommendations Downloaded from http://ahajournals.org by on October 7, 2026