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CLINICAL STATEMENTS AND GUIDELINES

April 1, 2025 Circulation. 2025;151:e771–e862. DOI: 10.1161/CIR.0000000000001309 e788

used solely to mask these symptoms. Concerns have also been raised that the use of opiates may delay gastric and intestinal absorption of orally administered P2Y12 inhibitors, thereby delaying their pharmacodynamic effects in patients undergoing PCI.7–10 However, the clinical relevance of these pharmacodynamic findings remains disputed.11–14 Use of nonaspirin nonsteroidal anti-inflammatory drugs should be avoided for management of suspected or known ischemia pain whenever possible.15–17 Use of nonsteroidal anti-inflammatory drugs is associated with increased risk of MACE in patients with and without prior cardiac disease, with no documented benefit to support routine use in patients with ACS.15–19

4.3 Antiplatelet Therapy

4.3.1 Aspirin

Recommendation for Aspirin Referenced studies that support recommendations are summarized in the Evidence Table.

COR LOE Recommendation

1 A 1 In patients with ACS, an initial oral loading

dose of aspirin, followed by daily low-dose aspirin, is recommended to reduce death and MACE.1–5

Synopsis Aspirin has long been considered an integral part of antiplatelet therapy to prevent recurrent atherothrombotic events among patients with ACS.1–3,6 Aspirin reduces the incidence of vascular death after AMI,3 and in secondary prevention trials (that include patients after MI), it reduces the occurrence of vascular and coronary events, including MI and stroke.2 Although aspirin use after ACS was traditionally considered lifelong, a strategy of aspirin discontinuation, rather than P2Y12 inhibitor discontinuation, may now be considered in the maintenance phase after 1 to 3 months in selected patients to reduce risk of bleeding (Section 11.1, “DAPT Strategies in the First 12 Months Postdischarge”). Aspirin discontinuation after 1 to 4 weeks after PCI is also appropriate for patients on a full-dose anticoagulant in combination with continued use of a P2Y12 inhibitor (Section 11.1.1, “Antiplatelet Therapy in Patients on Anticoagulation Postdischarge”). For patients in whom a history of aspirin hypersensitivity is reported, aspirin desensitization is preferred whenever possible to allow for initial use of dual antiplatelet therapy.7–9 The use of a P2Y12 inhibitor is recommended in all patients with ACS regardless of whether they have a history of aspirin hypersensitivity, but should be administered with a loading dose as early as possible for those patients unable to take aspirin at presentation.

Recommendation-Specific Supportive Text

1 Aspirin should be initiated with a loading dose

(162-325 mg) in patients with ACS without an absolute contraindication as soon as possible on presentation irrespective of final management strategy (invasive or noninvasive), followed by a daily maintenance dose (Table 7 in Section 4.3.2, “Oral P2Y12 Inhibitors During Hospitalization”). In patients who cannot take oral medication, rectal or intravenous (where available) administration are options for administration. Current evidence supports the use of uncoated low-dose aspirin (75- 100 mg) for daily maintenance therapy. The 75 to 100 mg daily dose of aspirin exceeds the minimal effective dose required for platelet thromboxane A2 suppression, allowing for some interindividual variability in drug response.10 Among patients with ACS referred for an invasive strategy, continued use of full-dose aspirin (300-325 mg daily) for 30 days (following an initial loading dose) was not superior to low-dose aspirin (75-100 mg daily) for reduction of MACE but was associated with increased minor and gastrointestinal bleeding.4 In an open-label

Table 6.  Analgesic Treatment Options for Cardiac Chest Pain Medication Route Suggested Dosing Considerations Nitroglycerin* SL (tablets, spray) 0.3 or 0.4 mg every 5 min as needed up to a total of 3 doses Use in hemodynamically stable patients with SBP ≥90 mm Hg. Nitroglycerin* IV Start at 10 μg/min and titrate to pain relief and hemodynamic tolerability. Consider for persistent anginal pain after oral nitrate therapy, or if ACS is accompanied by hypertension or pulmonary edema.20–22 Avoid use in suspected RV infarction, SBP <90 mm Hg or a change in SBP >30 mm Hg below baseline. Tachyphylaxis may occur after approximately 24 h. Morphine IV 2-4 mg; may repeat if needed every 5-15 min. Doses up to 10 mg may be considered. Use for relief of pain that is resistant to other maximally tolerated anti-ischemic medications. May delay the effects of oral P2Y12 therapy.7,9–12 Monitor closely for adverse effects. Fentanyl IV 25-50 μg; may repeat if needed. Doses up to 100 μg may be considered. Use for relief of pain that is resistant to other maximally tolerated anti-ischemic medications. May delay the effects of oral P2Y12 therapy.8 Monitor closely for adverse effects. *Nitrates should not be administered after recent PDE5 inhibitor use. Avoid use of nitrates/nitroglycerin within 12 h of avanafil, 24 h of sildenafil/vardenafil, or 48 h of tadalafil.23–25

ACS indicates acute coronary syndromes; PDE5, phosphodiesterase-5 inhibitor; RV, right ventricular; SBP, systolic blood pressure; and SL, sublingual.

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