What is the appropriate dosing of oral nitrates after a ST-Elevation Myocardial Infarction (STEMI)?

From the Guidelines

Oral nitrates should not be used routinely in the convalescent phase of STEMI, as they do not attenuate myocardial injury associated with epicardial coronary artery occlusion. According to the 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction 1, nitrates are not recommended for routine use in the convalescent phase of STEMI. The guideline suggests that intravenous nitroglycerin may be useful to treat patients with STEMI and hypertension or heart failure, but oral nitrates are not indicated for routine use.

When considering the use of nitrates, it's essential to weigh the potential benefits against the risks, including hypotension, marked bradycardia or tachycardia, and RV infarction. Additionally, nitrates should not be given to patients who have used 5'phosphodiesterase inhibitors within the previous 24 to 48 hours 1.

Key considerations for nitrate use include:

• Contraindications: hypotension, marked bradycardia or tachycardia, RV infarction, or 5'phosphodiesterase inhibitor use within the previous 24 to 48 hours
• Potential benefits: reducing LV preload and increasing coronary blood flow, but not attenuating myocardial injury associated with epicardial coronary artery occlusion
• Alternative treatments: other medications or therapies may be more effective in improving outcomes for patients after STEMI, and should be considered instead of oral nitrates.

From the FDA Drug Label

Attempts to overcome tolerance by dose escalation, even to doses far in excess of those used acutely, have consistently failed. Only after nitrates have been absent from the body for several hours has their antianginal efficacy been restored Isosorbide mononitrate extended-release tablets, during long-term use over 42 days dosed at 120 mg once daily, continued to improve exercise performance at 4 hours and at 12 hours after dosing The mean plasma elimination half-life of ISMN is approximately 5 hours.

The dosing of oral nitrates after a STEMI is not directly addressed in the provided drug label. However, based on the information about the pharmacokinetics and pharmacodynamics of isosorbide mononitrate, nitrate tolerance can be a concern with continuous dosing.

• The drug label suggests that tolerance can be avoided by allowing a nitrate-free interval of several hours.
• The elimination half-life of isosorbide mononitrate is approximately 5 hours.
• Dose escalation does not overcome tolerance. Given the information provided, a conservative approach would be to dose oral nitrates in a way that allows for a nitrate-free interval, but the exact dosing schedule after a STEMI is not specified in the label 2.

From the Research

Oral Nitrate Dosing after STEMI

• The use of nitrates in patients with STEMI (ST-Elevation Myocardial Infarction) is a common practice to reduce ischemic episodes and improve symptoms 3, 4.
• Studies have shown that oral nitrate dosing can be effective in reducing angina episodes and improving exercise tolerance in patients with STEMI 4, 5.
• However, the development of nitrate tolerance is a significant concern, which can be prevented by using a once-daily sustained-release formulation of isosorbide mononitrate 6, 7, 5.
• A daily low-nitrate interval is required to prevent tolerance development, and a 12-h patch-free interval or a nitrate-free period during each 24 h dosing interval can help prevent tolerance 6, 3.

Dosage and Administration

• The recommended dosage of isosorbide mononitrate for STEMI patients is 20 mg t.i.d. or 50 mg once daily using a sustained-release formulation 4, 5.
• The use of a sustained-release formulation can provide a rapid rise in plasma nitrate concentration and maintain prolonged efficacy throughout the dosing interval 5.
• Treatment should be started at low doses and gradually increased, with a free period usually at night, which can be covered by other anti-ischaemic drugs if necessary 3.

Efficacy and Safety

• Studies have shown that oral nitrate dosing can be safely used in patients with STEMI without the risk of hemodynamic deterioration, and can help prevent post-infarction angina 4.
• The use of nitrates can also improve exercise tolerance and reduce the frequency of angina episodes in patients with STEMI 7, 5.
• However, nitrates can cause adverse effects such as headache, postural hypotension, and facial erythema, which can be controlled by dosage adaptation 3.