What is the diagnosis and treatment for Non-ST-Elevation Myocardial Infarction (NSTEMI)?

From the Guidelines

The diagnosis and treatment of Non-ST-Elevation Myocardial Infarction (NSTEMI) should prioritize antithrombotic treatment with aspirin and parenteral anticoagulation, along with ticagrelor as the preferred P2Y12 inhibitor over clopidogrel, especially in patients not at high bleeding risk and intended for a conservative treatment strategy. The management of NSTEMI involves a multifaceted approach, including the use of antiplatelet and anticoagulant therapies to prevent further clot formation, as well as medications to address the underlying atherosclerotic disease and protect the heart from further damage. According to the 2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation 1, the choice of antithrombotic regimen should be based on the selected management strategy and revascularization modality.

Key components of the treatment include:

• Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor, with ticagrelor preferred over clopidogrel in patients not at high bleeding risk and intended for conservative treatment 1
• Anticoagulation with heparin or low molecular weight heparin
• High-intensity statins to address the underlying atherosclerotic disease
• Beta-blockers to protect the heart from further damage and adverse remodeling
• ACE inhibitors or ARBs for patients with reduced ejection fraction or diabetes

Early cardiac catheterization (within 24-72 hours) is also recommended for most patients to determine if revascularization is needed, as this approach can help improve outcomes by addressing both the immediate clot formation and the underlying disease process. The dosing of antithrombotic agents should take into account patient age and renal function, as emphasized in the guidelines 1.

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.

1.1 Acute Coronary Syndrome (ACS) 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

The diagnosis of Non-ST-Elevation Myocardial Infarction (NSTEMI) is not directly addressed in the provided drug labels. The treatment for NSTEMI includes the use of antiplatelet agents such as prasugrel and clopidogrel to reduce the rate of thrombotic CV events, in conjunction with aspirin and management with percutaneous coronary intervention (PCI) or coronary revascularization. The dosing regimens for prasugrel and clopidogrel are as follows:

• Prasugrel: a single 60 mg oral loading dose and then 10 mg orally once daily
• Clopidogrel: a single 300 mg oral loading dose and then 75 mg once daily It is essential to consider the patient's individual characteristics, such as weight and history of bleeding, when selecting a treatment regimen 23.

From the Research

Diagnosis and Treatment of Non-ST-Elevation Myocardial Infarction (NSTEMI)

• The diagnosis and treatment of NSTEMI involve an invasive strategy with cardiac catheterization, revascularization when clinically appropriate, and initiation of dual antiplatelet therapy regardless of whether the patient receives revascularization 4.
• 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 5.
• The challenges for the treatment of patients with NSTEMI can be categorized into four "P" factors that contribute to poor clinical outcomes: patient characteristics being heterogeneous; physicians underestimating the high ischemic risk compared with bleeding risk; procedure availability; and policy within the healthcare system 4.

Anticoagulation Therapy

• Unfractionated heparin (UFH) has been the unchallenged mainstay in anticoagulation for ACS for many decades and is still widely used in patients with ACS treated interventionally 5.
• Novel alternative parenteral anticoagulant strategies include the low molecular weight heparin enoxaparin and the synthetic pentasaccharide fondaparin 5.
• The direct parenteral factor IIa (thrombin) inhibitor bivalirudin, when used as sole anticoagulant in patients with ACS undergoing PCI, is as effective as the regimen of UFH plus GPIIb/IIIa inhibitor in NSTEMI and superior to the latter regimen in patients with STEMI 5.

Oral P2Y12 Inhibitors

• Potent P2Y12 inhibition with the use of prasugrel or ticagrelor is the mainstay of treatment after an acute coronary syndrome (ACS) 6.
• Prasugrel resulted in a reduction of the composite cardiovascular end point both versus clopidogrel and ticagrelor in patients intended to receive invasive management 6.
• Prasugrel ranked as the most efficient treatment in the composite cardiovascular efficacy outcome, all-cause death, myocardial infarction and definite stent thrombosis, while clopidogrel ranked as safest in the bleeding outcomes 6.
• Newer oral P2Y12 inhibitors (prasugrel or ticagrelor) significantly decreased major cardiovascular events (MACE) and myocardial infarction (MI) at the expense of a significant increase in the risk of bleeding compared to clopidogrel 7.