What are the diagnosis and management strategies for Non-ST-Elevation Myocardial Infarction (NSTEMI)?

From the Guidelines

NSTEMI diagnosis and management should prioritize immediate dual antiplatelet therapy with aspirin and a P2Y12 inhibitor, such as ticagrelor, along with anticoagulation and high-intensity statins, with an early invasive strategy using coronary angiography within 24-72 hours for most patients. The management of NSTEMI is guided by the principles of reducing morbidity, mortality, and improving quality of life. 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 NSTEMI Management

• Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor, such as ticagrelor (preferred over clopidogrel) 1, is crucial for reducing recurrent cardiovascular events.
• Anticoagulation with unfractionated heparin, low molecular weight heparin, or fondaparinux should be initiated promptly to prevent further thrombosis.
• High-intensity statins, such as atorvastatin or rosuvastatin, are recommended for all patients with NSTEMI to reduce morbidity and mortality.
• Beta-blockers and ACE inhibitors or ARBs should be used in patients with left ventricular dysfunction to improve outcomes.
• Pain management with nitroglycerin and morphine may be necessary for symptomatic relief.

Invasive Strategy

Most NSTEMI patients should undergo an early invasive strategy with coronary angiography within 24-72 hours, with timing based on risk stratification 1. High-risk features warranting urgent intervention include hemodynamic instability, recurrent angina, heart failure, or electrical instability. The 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 guidelines for the management of patients with unstable angina/NSTEMI also supports the use of an early invasive strategy for high-risk patients 1.

Secondary Prevention

Following the acute phase, secondary prevention includes lifelong aspirin, P2Y12 inhibitor for 6-12 months, statins, beta-blockers, and ACE inhibitors/ARBs as indicated, along with risk factor modification addressing hypertension, diabetes, smoking cessation, and cardiac rehabilitation. This comprehensive approach reduces mortality and recurrent cardiovascular events by addressing both the acute thrombotic process and underlying atherosclerotic disease. The most recent and highest quality study, the 2015 ESC guidelines 1, provides the basis for these recommendations, prioritizing morbidity, mortality, and quality of life as the primary outcomes.

From the FDA Drug Label

In the clinical trial that established the efficacy and safety of prasugrel tablets, the loading dose of prasugrel tablets was not administered until coronary anatomy was established in UA/NSTEMI patients and in STEMI patients presenting more than 12 hours after symptom onset 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) The primary outcome measure was the composite of cardiovascular death, nonfatal MI, or nonfatal stroke in the UA/NSTEMI population.

The diagnosis and management of NSTEMI involves the use of prasugrel to reduce the rate of thrombotic CV events. Key considerations include:

• Administering the loading dose of prasugrel after coronary anatomy is established in UA/NSTEMI patients
• Using prasugrel in combination with aspirin (75 mg to 325 mg) daily
• Considering a lower maintenance dose (5 mg) in patients weighing <60 kg due to increased exposure to the active metabolite and risk of bleeding
• Monitoring for bleeding events, as prasugrel increases the risk of bleeding, particularly in patients with a history of prior transient ischemic attack or stroke 2.

From the Research

Diagnosis of NSTEMI

• NSTEMI is defined as elevated cardiac biomarkers of necrosis in the absence of persistent ST-segment elevation in the setting of anginal symptoms or other acute event 3
• It can result from an acute atherothrombotic event ('Type 1') or as the result of other causes of mismatch of myocardial oxygen supply and demand ('Type 2') 3, 4
• Type 1 MI has a different underlying pathophysiology than type 2 through type 5 MI; type 1 MI is characterized primarily by intracoronary atherothrombosis and the other types by a variety of mechanisms, which can occur with or without an atherosclerotic component 4

Management of NSTEMI

• Dual antiplatelet therapy (DAPT) with aspirin and the P2Y12 receptor inhibitor clopidogrel significantly reduces the ischemic events in NSTEMI patients and has represented the mainstay of treatment for over a decade 5
• Novel generation P2Y12 receptor blockers, such as prasugrel and ticagrelor, or adjunctive antiplatelet or anticoagulant therapies, such as vorapaxar or rivaroxaban, respectively, may be used for more potent antithrombotic treatment regimens for the long-term prevention of atherothrombotic events in NSTEMI patients 5
• Prasugrel resulted in a reduction of the composite cardiovascular end point both versus clopidogrel and ticagrelor in patients intended to receive invasive management 6
• The 2020 European Society of Cardiology (ESC) Guidelines recommend the use of prasugrel over ticagrelor in patients with non-ST-elevation ACS (NSTE-ACS) intended to receive invasive management (class IIa recommendation) 6

Treatment Strategies

• The hospital medicine specialist is increasingly responsible for managing or coordinating the care of NSTEMI patients, and following published guidelines for risk stratification and basing anti-anginal, anticoagulant, antiplatelet, other pharmacologic therapies, and overall management approach on that individualized patient risk assessment can be expected to result in better short- and long-term clinical outcomes 3
• Prolonging intensified antiplatelet therapy beyond 1 year has also been investigated, but although intensified and prolonged antithrombotic treatment regimens reduce ischemic events, this occurs at the expense of an increased risk of bleeding complications 5, 7
• The clinical management of ACS patients undergoing PCI has evolved significantly in the last 2 decades, with a shift toward more rapid invasive management, broader use of drug-eluting stents, and the increasing recognition that major bleeding due to antiplatelet therapy is detrimental 7