What is the management of inferior ST-elevation myocardial infarction (STEMI) with nitroglycerin (glyceryl trinitrate)?

From the Guidelines

Nitroglycerin should be used with caution in patients with inferior ST-elevation myocardial infarction (STEMI) and its use is generally not recommended unless the patient has hypertension or heart failure, as stated in the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction 1. When considering the use of nitroglycerin in inferior STEMI, it is crucial to rule out right ventricular involvement by obtaining right-sided ECG leads, such as V4R, as recommended in the 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation 1. Some key points to consider when managing inferior STEMI include:

• The primary treatment for inferior STEMI remains urgent reperfusion therapy via primary percutaneous coronary intervention (PCI) or fibrinolysis if PCI is not available within 120 minutes.
• If right ventricular infarction is present, management should focus on maintaining adequate preload with IV fluids, such as normal saline boluses of 500-1000mL, reassessing after each bolus.
• For pain management in these patients, consider morphine sulfate (2-4mg IV) instead of nitroglycerin.
• If nitroglycerin must be used in patients without right ventricular involvement, start with a low dose (0.4mg sublingual or 5-10mcg/min IV) and monitor blood pressure closely, as recommended in the 2013 ACCF/AHA guideline 1. It is essential to prioritize the patient's hemodynamic stability and consider alternative treatments, such as morphine sulfate, for pain management in inferior STEMI patients with right ventricular involvement.

From the FDA Drug Label

The benefits of sublingual nitroglycerin in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use nitroglycerin in these conditions, careful clinical or hemodynamic monitoring must be used because of the possibility of hypotension and tachycardia. The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle. Although venous effects predominate, nitroglycerin produces, in a dose-related manner, dilation of both arterial and venous beds Dilation of postcapillary vessels, including large veins, promotes peripheral pooling of blood, decreases venous return to the heart, and reduces left ventricular end-diastolic pressure (preload)

• Inferior STEMI: The FDA drug label does not provide specific information about the use of nitroglycerin in inferior STEMI.
• Nitroglycerin administration: The label warns that the benefits of sublingual nitroglycerin in patients with acute myocardial infarction have not been established, and careful monitoring is required due to the possibility of hypotension and tachycardia 2. In general, nitroglycerin can reduce systolic, diastolic, and mean arterial blood pressure, and can decrease myocardial oxygen consumption. However, the label does not provide specific guidance on the use of nitroglycerin in inferior STEMI 2.

From the Research

Inferior STEMI and Nitroglycerin Administration

• The administration of nitroglycerin (NTG) to patients with inferior ST elevation myocardial infarction (STEMI) has been studied to determine its safety and effectiveness 3, 4, 5.
• A study published in 2016 found that NTG administration to patients with inferior STEMI is not associated with a higher rate of hypotension compared to patients with STEMI in other territories 3.
• Another study published in 2019 found that field NTG did not result in a clinically significant decrease in blood pressure when compared with patients who did not receive NTG, but it did cause a clinically significant reduction in pain 4.
• A systematic review and meta-analysis published in 2023 found that the use of nitrates during right ventricular myocardial infarction (RVMI) is not associated with an increased risk of adverse events, and that nitrates may be a reasonable treatment modality to consider during RVMI 5.

Mechanisms and Risks

• Nitroglycerin achieves its benefit by giving rise to nitric oxide (NO), which causes vasodilation and increases blood flow to the myocardium 6.
• However, continuous delivery of GTN results in tolerance, limiting the use of this drug, and sustained treatment may negatively affect cardiomyocyte viability following ischemia, resulting in increased infarct size 6.
• Coadministration of Alda-1, an activator of ALDH2, with GTN may improve metabolism of reactive aldehyde adducts and prevent the GTN-induced increase in cardiac dysfunction following MI 6.

Clinical Implications

• The current guidelines of the American Heart Association (AHA) and European Society of Cardiology (ESC) recommend that when right ventricular myocardial infarction (RVMI) is present, patients are not administered nitrates, due to the risk of decreasing preload and precipitating hypotension 5.
• However, the evidence suggests that this contraindication may not be supported by evidence, and that nitrates may be a reasonable treatment modality to consider during RVMI 5.
• Further studies are needed to fully understand the benefits and risks of NTG administration in patients with inferior STEMI and RVMI 3, 4, 5.