Is IMDUR (isosorbide mononitrate) used in the treatment of acute myocardial infarction?

IMDUR (Isosorbide Mononitrate) in Acute Myocardial Infarction

IMDUR should NOT be routinely used in acute myocardial infarction, as large randomized trials and current guidelines demonstrate no mortality benefit and the FDA explicitly states that benefits in acute MI have not been established. 1, 2

Evidence Against Routine Use

The totality of evidence from major clinical trials does not support routine nitrate therapy in acute MI:

• The ISIS-4 trial (58,050 patients) compared 28-day treatment of controlled-release oral isosorbide mononitrate versus placebo and found only a small, nonsignificant reduction in 35-day mortality (7.34% versus 7.54%). 1

• The GISSI-3 trial (19,394 patients) tested routine intravenous nitrate administration versus selective use and found no significant mortality reduction at 6 weeks. 1

• Meta-analysis of all randomized trials shows only a small 5.5% ± 2.6% relative mortality reduction (p=0.003), representing approximately 4 lives saved per 1000 treated—a clinically marginal benefit that does not justify routine use. 1, 3

• The 2017 European Society of Cardiology guidelines explicitly state that routine use of nitrates in STEMI was of no benefit in randomized controlled trials and is therefore not recommended. 1, 3

FDA Position on IMDUR in Acute MI

The FDA drug label clearly states: "The benefits of ISMN in patients with acute myocardial infarction have not been established; because the effects of isosorbide mononitrate are difficult to terminate rapidly, this drug is not recommended in these settings." 2

If IMDUR is used in acute MI, the FDA mandates careful clinical or hemodynamic monitoring to avoid the hazards of hypotension and tachycardia. 2

When Nitrates ARE Indicated in Acute MI

Use intravenous nitroglycerin (NOT IMDUR) for the first 24-48 hours in patients with acute MI who have: 1, 4

• Recurrent ischemia
• Congestive heart failure
• Hypertension requiring management

Why IV Nitroglycerin Over IMDUR:

• Nitroglycerin is the only nitrate available for intravenous use in the United States. 4
• Half-life of only several minutes allows for rapid titration and prompt termination if side effects occur. 1, 4
• IMDUR has a 12-24 hour duration of action, making effects difficult to terminate rapidly—a critical disadvantage in the unstable acute MI setting. 5, 2

IV Nitroglycerin Protocol:

• Starting dose: 5-10 mcg/min, titrated by 10 mcg/min every 3-5 minutes based on blood pressure and symptom response. 4, 3
• Maximum dose typically 200 mcg/min. 4
• **Avoid systolic BP <90 mmHg** or >30 mmHg below baseline. 4

Transition to Oral Nitrates

Transition to oral or topical nitrates (including IMDUR) only in patients with CHF and large transmural MIs after the acute phase (>48 hours). 1, 3

If oral isosorbide mononitrate is used:

• Provide a nitrate-free interval of at least 10-14 hours daily to prevent tolerance development. 4, 5
• Tolerance typically develops after 24 hours of continuous therapy. 4

Critical Safety Contraindications

Absolute contraindications for any nitrate use in acute MI: 4, 5, 3

• Sildenafil use within 24 hours or tadalafil use within 48 hours—risk of profound hypotension, MI, and death
• Systolic BP <90 mmHg
• Inferior wall MI with suspected right ventricular involvement—these patients depend on adequate RV preload and can experience profound hypotension during nitrate administration

Common Pitfalls to Avoid

1. Do not use IMDUR for acute symptom relief—the FDA label explicitly states that onset of action is not sufficiently rapid for aborting an acute anginal episode. 2

2. Do not use IMDUR when rapid titration is needed—its prolonged duration of action (12-24 hours) prevents rapid adjustment in the hemodynamically unstable acute MI patient. 5, 2

3. Do not assume all nitrates are equivalent—IV nitroglycerin's short half-life and titratability make it vastly superior to IMDUR in acute settings. 1, 4

4. Monitor for hypotension and reflex tachycardia, which can worsen myocardial ischemia. 5, 2

Bottom Line Algorithm

For uncomplicated acute MI: No routine nitrate therapy of any kind. 1, 3

For acute MI with recurrent ischemia, CHF, or hypertension: Use IV nitroglycerin (not IMDUR) for 24-48 hours. 1, 4

For post-MI patients with persistent CHF and large transmural infarcts: Consider transitioning to oral IMDUR after 48 hours with mandatory 10-14 hour nitrate-free interval. 4, 3

IMDUR is FDA-approved only for prevention of angina pectoris due to coronary artery disease—not for acute MI management. 2