What are the standard acute treatment protocols for acute coronary syndrome (ACS), including ST-elevation myocardial infarction (STEMI) and non-ST-elevation ACS (NSTE-ACS), and what is the role of antiplatelet, anticoagulant, and beta-blocker therapy in its management?

From the Guidelines

The standard acute treatment protocol for acute coronary syndrome (ACS) involves immediate medical intervention with antiplatelet, anticoagulant, and beta-blocker therapies, with specific approaches for ST-elevation myocardial infarction (STEMI) versus non-ST-elevation ACS (NSTE-ACS), as recommended by the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1. For STEMI, immediate reperfusion therapy is crucial, preferably primary percutaneous coronary intervention (PCI) within 90 minutes of first medical contact, or fibrinolytic therapy within 30 minutes if PCI is unavailable. For NSTE-ACS, an early invasive strategy is recommended for high-risk patients, while conservative management may be appropriate for lower-risk cases.

Antiplatelet Therapy

Antiplatelet therapy begins with aspirin (162-325mg loading dose, then 81mg daily) for all ACS patients, as recommended by the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1. A P2Y12 inhibitor is added: ticagrelor (180mg loading, 90mg twice daily) or prasugrel (60mg loading, 10mg daily) are preferred over clopidogrel (600mg loading, 75mg daily) according to the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline 1. Dual antiplatelet therapy typically continues for 12 months.

Anticoagulation

Anticoagulation includes unfractionated heparin (60 U/kg IV bolus, then 12 U/kg/hr), low molecular weight heparin (enoxaparin 1mg/kg twice daily), or bivalirudin (0.75 mg/kg bolus, then 1.75 mg/kg/hr infusion), as outlined in the 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes 1.

Beta-Blockers

Beta-blockers (metoprolol 5mg IV every 5 minutes for 3 doses, then 25-100mg orally twice daily) should be initiated within 24 hours if no contraindications exist.

Additional Interventions

Additional immediate interventions include oxygen therapy for hypoxemic patients, sublingual nitroglycerin for ongoing chest pain, and morphine for pain unresponsive to nitrates. High-dose statins (atorvastatin 80mg daily) should be started promptly. ACE inhibitors or ARBs are indicated for patients with left ventricular dysfunction. This comprehensive approach targets reducing myocardial oxygen demand, preventing further thrombosis, and achieving myocardial reperfusion to limit infarct size and improve outcomes.

Clinical Circumstances for Withholding Therapy

Acute antiplatelet and/or anticoagulant therapy is typically withheld in patients with active bleeding, severe thrombocytopenia, or other contraindications to these therapies, as noted in the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1.

Delaying Anticoagulation and Antiplatelet Therapy

It is not preferable to delay the immediate initiation of anticoagulation and antiplatelet therapy when a cardiac catheterization lab is readily accessible, as prompt treatment is crucial for improving outcomes in ACS patients, according to the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1.

Role of Beta-Blockers

Beta-blockers play a crucial role in the management of ACS, as they reduce myocardial oxygen demand and improve survival, and should be initiated within 24 hours if no contraindications exist, as recommended by the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1. Some key points to consider in the management of ACS include:

• A strategy of complete revascularization is recommended in patients with ST-segment elevation myocardial infarction or non–ST-segment elevation ACS, as outlined in the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1.
• The choice of revascularization method (ie, coronary artery bypass graft surgery versus multivessel PCI) in non–ST-segment elevation ACS and multivessel disease should be based on the complexity of the coronary artery disease and comorbid conditions.
• PCI of significant nonculprit stenoses for patients with ST-segment elevation myocardial infarction can be performed in a single procedure or staged with some preference toward performing multivessel PCI in a single procedure.
• In patients with ACS and cardiogenic shock, emergency revascularization of the culprit vessel is indicated; however, routine PCI of non–infarct-related arteries at the time of PCI is not recommended, as noted in the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1.

From the FDA Drug Label

The effectiveness of clopidogrel tablets results from its antiplatelet activity, which is dependent on its conversion to an active metabolite by the cytochrome P450 (CYP) system, principally CYP2C19 [see Warnings and Precautions(5. 1), Clinical Pharmacology(12.3)]. Clopidogrel tablets are indicated to reduce the rate of myocardial infarction (MI) and stroke in patients with non-ST-segment elevation ACS (unstable angina [UA]/non-ST -elevation myocardial infarction [NSTEMI]), including patients who are to be managed medically and those who are to be managed with coronary revascularization Clopidogrel tablets are indicated to reduce the rate of myocardial infarction and stroke in patients with acute ST-elevation myocardial infarction (STEMI) who are to be managed medically. Ticagrelor tablets are indicated to reduce the risk of cardiovascular (CV) death, myocardial infarction (MI), and stroke in patients with acute coronary syndrome (ACS) or a history of MI.

The standard acute treatment protocols for ST-elevation myocardial infarction (STEMI) and non-ST-elevation ACS (NSTE-ACS) include the administration of antiplatelet and anticoagulant therapy.

• For STEMI, the treatment protocol includes the administration of aspirin and clopidogrel or ticagrelor, with or without anticoagulant therapy.
• For NSTE-ACS, the treatment protocol includes the administration of aspirin, clopidogrel or ticagrelor, and anticoagulant therapy. The specific clinical circumstances under which acute antiplatelet and/or anticoagulant therapy is typically withheld include:
• Active bleeding or a history of intracranial hemorrhage
• Hypersensitivity to the medication
• Use of other medications that may interact with antiplatelet or anticoagulant therapy It is not preferable to delay the immediate initiation of anticoagulation and antiplatelet therapy when a cardiac catheterization lab is readily accessible, as prompt treatment is essential to reduce the risk of cardiovascular events. The current guidelines and role of beta-blockers in the management of ACS recommend the use of beta-blockers in patients with ACS, unless contraindicated, to reduce the risk of cardiovascular events 2 3.
• Beta-blockers should be administered as soon as possible after the diagnosis of ACS is made, and continued indefinitely in patients with a history of MI.
• The use of beta-blockers in patients with ACS has been shown to reduce the risk of cardiovascular events, including myocardial infarction and stroke. Key points to consider:
• Antiplatelet therapy: Aspirin, clopidogrel, or ticagrelor should be administered to all patients with ACS, unless contraindicated.
• Anticoagulant therapy: Anticoagulant therapy, such as heparin or low-molecular-weight heparin, should be administered to patients with ACS, unless contraindicated.
• Beta-blocker therapy: Beta-blockers should be administered to all patients with ACS, unless contraindicated.

From the Research

Standard Acute Treatment Protocols for STEMI and NSTE-ACS

• The standard acute treatment protocols for STEMI include immediate referral to cardiac catheterization and the administration of aspirin and a second antiplatelet agent, such as clopidogrel, ticagrelor, or prasugrel, unless contraindicated 4.
• For NSTE-ACS, the current guidelines of the European Society of Cardiology (ESC) recommend the use of high-sensitivity cardiac troponin assay (hs-cTn) combined with verified diagnostic algorithms to enable a rapid triage decision 5.
• The management of NSTE-ACS also involves the use of antithrombotic treatment, invasive or non-invasive coronary diagnostics, and long-term treatment, as outlined in the ESC guidelines 5.

Clinical Circumstances for Withholding Antiplatelet and/or Anticoagulant Therapy

• Antiplatelet and/or anticoagulant therapy may be withheld in patients with a high risk of bleeding, such as those with active gastrointestinal bleeding or a history of bleeding disorders 4.
• The decision to withhold antiplatelet and/or anticoagulant therapy should be made on a case-by-case basis, taking into account the individual patient's risk factors and clinical circumstances 4.

Delaying Initiation of Anticoagulation and Antiplatelet Therapy

• The initiation of anticoagulation and antiplatelet therapy should not be delayed when a cardiac catheterization lab is readily accessible, as prompt treatment is essential for improving outcomes in patients with ACS 4.
• However, the timing of initiation of anticoagulation and antiplatelet therapy may vary depending on the individual patient's clinical circumstances and the availability of cardiac catheterization facilities 4.

Role of Beta-Blockers in the Management of ACS

• Beta-blockers are recommended for all patients with ACS, unless contraindicated, as they have been shown to reduce mortality and morbidity in these patients 4.
• The use of beta-blockers in the management of ACS is supported by the American Heart Association (AHA) and the American College of Cardiology (ACC) guidelines, as well as the ESC guidelines 4, 6.
• Beta-blockers should be initiated as soon as possible after diagnosis, and continued indefinitely in patients with a history of ACS, unless contraindicated 4.

Antiplatelet Therapy in ACS

• Antiplatelet therapy is a cornerstone of treatment for ACS, and includes the use of aspirin and a second antiplatelet agent, such as clopidogrel, ticagrelor, or prasugrel 7, 8.
• The choice of antiplatelet agent depends on the individual patient's clinical circumstances, including their risk of bleeding and their planned treatment strategy 7, 8.
• Novel antiplatelet agents, such as intravenous P2Y12 antagonists and oral PAR-1 antagonists, are being developed and may offer improved efficacy and safety compared to existing agents 7, 8.