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CLINICAL STATEMENTS AND GUIDELINES

Circulation. 2025;151:e771–e862. DOI: 10.1161/CIR.0000000000001309 April 1, 2025 e789

RCT of patients with established atherosclerotic cardiovascular disease (ASCVD), 35% of whom had a previous MI, no significant differences were observed in MACE or major bleeding for patients treated with 81 mg of aspirin daily and those treated with 325 mg daily, although a high degree of crossover between study arms was observed.5 Together, these data support the use of low-dose aspirin (75-100 mg daily) for maintenance therapy. Based on an association between aspirin dosing and outcomes in a post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, aspirin doses of ≤100 mg daily should always be used in patients treated with ticagrelor.11

4.3.2 Oral P2Y12 Inhibitors During Hospitalization

Recommendations for Oral P2Y12 Inhibitors During Hospitalization Referenced studies that support recommendations are summarized in the Evidence Table.

COR LOE Recommendations All Patients With ACS (STEMI and NSTE-ACS)

1 A 1 In patients with ACS, an oral P2Y12 inhibitor

should be administered in addition to aspirin to reduce MACE.1–5

3: Harm B-R 2 In patients with a history of stroke or transient

ischemic attack, prasugrel should not be administered because of worse net clinical outcomes.*†4

In-Hospital Management in Patients With NSTE-ACS

1 B-R 3.	 In patients with NSTE-ACS undergoing PCI,

prasugrel or ticagrelor is recommended to reduce MACE and stent thrombosis.4–6

1 B-R 4 In patients with NSTE-ACS who are managed

without planned invasive evaluation, ticagrelor is recommended to reduce MACE.5,7

1 B-R 5 In patients with NSTE-ACS, clopidogrel is

recommended to reduce MACE when prasugrel or ticagrelor are unavailable, cannot be tolerated, or are contraindicated.1 2b B-NR 6 In patients with NSTE-ACS planned for an inva-

sive strategy with timing of angiography anticipated to be >24 hours, upstream treatment with clopidogrel or ticagrelor may be considered to reduce MACE.1,5,8

In-Hospital Management in Patients With STEMI

1 B-R 7.	 In patients with STEMI managed with PPCI,

prasugrel or ticagrelor should be administered to reduce MACE and stent thrombosis.4,5,9,10

1 C-LD 8.	 In patients with STEMI managed with PPCI,

clopidogrel is recommended to reduce MACE and stent thrombosis when prasugrel or ticagrelor are unavailable, cannot be tolerated, or are contraindicated.11

1 A 9 In patients with STEMI managed with fibrinolytic

therapy, clopidogrel should be administered concurrently to reduce death and MACE.2,3

*Modified from the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization”12 and the †”2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease.”13

Synopsis Oral inhibitors of the platelet P2Y12 receptor antagonize adenosine diphosphate–mediated activation of platelets. Across the spectrum of ACS, the addition of a P2Y12 inhibitor to aspirin significantly reduces platelet aggregation and has been shown to reduce the incidence of recurrent MACE but with an increased risk of bleeding.1–5,9,10 In addition to receiving aspirin, patients with ACS should therefore be treated with a loading dose of an oral P2Y12 inhibitor followed by daily dosing (Table 7). The selection of the specific type of oral P2Y12 inhibitor should involve several considerations, including the patient’s anticipated management strat-

Table 7.  Dosing Considerations for Oral Antiplatelet Therapy in Patients With ACS Agent Setting Dosing Considerations Aspirin NSTE-ACS or STEMI Loading dose 162-325 mg orally. Aspirin (nonenteric coated) should be chewed, when possible, to achieve faster onset of antiplatelet action. Loading dose should be administered for patients already on aspirin therapy.

Maintenance dose 75-100 mg orally daily (nonenteric coated)

Clopidogrel NSTE-ACS or STEMI without fibrinolytic Loading dose 300 or 600 mg orally

Maintenance 75 mg orally daily

STEMI with fibrinolytic Loading dose 300 mg orally if age ≤75 y; Initial dose 75 mg orally if age >75 y

Maintenance 75 mg orally daily

Prasugrel NSTE-ACS or STEMI without fibrinolytic, and undergoing PCI Loading dose 60 mg orally

Maintenance dose 10 mg orally daily if body weight ≥60 kg and age <75 y Maintenance dose 5 mg orally daily if body weight <60 kg or age ≥75 y (use caution)

Ticagrelor NSTE-ACS or STEMI without fibrinolytic Loading dose 180 mg orally

Maintenance dose 90 mg orally twice daily

NSTE-ACS indicates non–ST-segment elevation acute coronary syndromes; PCI, percutaneous coronary intervention; and STEMI, ST-segment elevation myocardial infarction.

Recommendations for Oral P2Y12 Inhibitors During Hospitalization (Continued )

COR LOE Recommendations

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