What are the 2025 guidelines for the management of Non-ST-Elevation Myocardial Infarction (NSTEMI)?

From the Guidelines

The 2025 guidelines for NSTEMI management recommend an initial selection of oral P2Y12 inhibitor, with aspirin + ticagrelor or prasugrel (Class 1) for patients undergoing PCI, and aspirin + clopidogrel (Class 1) for those undergoing CABG. According to the 2025 ACC/AHA/ACEP/NAEMSP/SCAI guideline for the management of patients with acute coronary syndromes 1, the initial choice of P2Y12 inhibitor is crucial in the management of NSTEMI.

Key Recommendations

• For patients undergoing PCI, aspirin + ticagrelor or prasugrel (Class 1) is recommended, with clopidogrel as an alternative when ticagrelor or prasugrel are not available, cannot be tolerated, or are contraindicated.
• For patients undergoing CABG, aspirin + clopidogrel (Class 1) is recommended, with aspirin + ticagrelor or clopidogrel (Class 1) as an alternative.
• For patients with no planned invasive evaluation, clopidogrel is recommended when ticagrelor is not available, cannot be tolerated, or is contraindicated.

Rationale

The guideline recommendations are based on the latest evidence and aim to reduce morbidity, mortality, and improve quality of life for patients with NSTEMI. The choice of P2Y12 inhibitor is critical in preventing recurrent ischemic events and reducing the risk of bleeding complications.

Clinical Implications

The 2025 guidelines provide a comprehensive approach to the management of NSTEMI, emphasizing the importance of early risk stratification, antiplatelet and anticoagulant therapy, and long-term management with DAPT and pharmacotherapy. By following these guidelines, clinicians can provide evidence-based care that improves patient outcomes and reduces the risk of recurrent events.

From the FDA Drug Label

1.1 Acute Coronary Syndrome Prasugrel tablets are indicated to reduce the rate of thrombotic CV events (including stent thrombosis) in patients with acute coronary syndrome (ACS) who are to be managed with percutaneous coronary intervention (PCI) as follows: Patients with unstable angina (UA) or non-ST-elevation myocardial infarction (NSTEMI) Patients with ST-elevation myocardial infarction (STEMI) when managed with primary or delayed PCI.

The 2025 guidelines on management of NSTEMI are not explicitly stated in the provided drug labels. However, according to the labels, prasugrel is indicated to reduce the rate of thrombotic CV events in patients with acute coronary syndrome (ACS), including those with NSTEMI, who are to be managed with percutaneous coronary intervention (PCI). The recommended dosage is a single 60 mg oral loading dose, followed by 10 mg orally once daily, in combination with aspirin (75 mg to 325 mg) daily 2.

From the Research

Management of NSTEMI

The management of non-ST-elevation myocardial infarction (NSTEMI) involves anticoagulation and antiplatelet therapy.

• Anticoagulants play a vital role as part of the antithrombotic therapy of myocardial infarction and are complementary to antiplatelet therapies 3.
• Patients presenting with NSTEMI should be initiated on anticoagulation (e.g. heparin/low molecular weight heparin) for the initial hospitalization period for those medically managed or until percutaneous coronary intervention 3.

Antithrombotic Therapy

Antithrombotic therapy in patients with NSTEMI comprises antiplatelet and anticoagulant therapy.

• Dual antiplatelet therapy composed of aspirin plus a third generation P2Y12 inhibitor (prasugrel or ticagrelor) represents the gold standard, while aspirin plus second generation P2Y12 inhibitor (clopidogrel) may be used as an alternative in the presence of contraindications for third generation P2Y12 inhibitors and/or a high risk of bleeding 4.
• Longer term management of NSTEMI for patients with an existing indication for long-term anticoagulation should comprise triple antithrombotic therapy of anticoagulant (preferably DOAC) with aspirin and clopidogrel for up to 1 month, followed by DOAC plus clopidogrel for up to 1 year, and then DOAC monotherapy thereafter 3.

Invasive and Antiplatelet Treatment

Clinical guidelines for the treatment of patients with NSTEMI recommend an invasive strategy with cardiac catheterization, revascularization when clinically appropriate, and initiation of dual antiplatelet therapy regardless of whether the patient receives revascularization.

• However, although patients with NSTEMI have a higher long-term mortality risk than patients with ST-segment elevation myocardial infarction (STEMI), they are often treated less aggressively; with those who have the highest ischemic risk often receiving the least aggressive treatment (the "treatment-risk paradox") 5.
• Potential approaches to address this issue include: developing guidelines and protocols that incorporate rigorous definitions of NSTEMI; risk assessment and integrated quality assessment measures; providing education to physicians on the management of long-term cardiovascular risk in patients with NSTEMI; and making stents and antiplatelet therapies more accessible to patients 5.

Antiplatelet and Anticoagulation Agents

Mortality and morbidity in acute coronary syndromes (ACSs) have been reduced by a combination of antithrombotic agents (antiplatelet drugs and anticoagulants) and early revascularization.

• Aspirin is the foundation antiplatelet agent, and new P2Y12 receptor inhibitors (prasugrel and ticagrelor) have clear benefits compared with clopidogrel for dual antiplatelet therapy 6.
• Anticoagulation uses 1 of 4 choices: bivalirudin, unfractionated heparin, enoxaparin, and fondaparinux, and some patients require triple therapy with aspirin, clopidogrel, plus an anticoagulant, frequently a vitamin K antagonist 6.

Oral Antithrombotic Therapy

Patients with NSTEMI are at high risk for atherothrombotic recurrences, and dual antiplatelet therapy (DAPT) with aspirin and the P2Y12 receptor inhibitor clopidogrel significantly reduces the ischemic events in NSTEMI patients.

• However, a considerable number of patients continue to experience thrombotic complications, which may be in part due to inadequate platelet inhibition induced by this treatment regimen, and novel generation P2Y12 receptor blockers, such as prasugrel and ticagrelor, or adjunctive antiplatelet or anticoagulant therapies, such as vorapaxar or rivaroxaban, may be used 7.