ISMN vs ISDN for Myocardial Infarction
For acute myocardial infarction, intravenous nitroglycerin is the preferred nitrate—not ISDN or ISMN—because it is the only IV nitrate available in the United States and offers superior titratability with its short half-life of several minutes. 1
Pharmacokinetic Differences
The key pharmacokinetic distinctions between these agents directly impact their clinical utility in MI:
ISDN undergoes extensive hepatic metabolism to two active metabolites (isosorbide-2-mononitrate and ISMN), with a half-life of 40-90 minutes and variable bioavailability due to first-pass metabolism 1
ISMN is the principal active metabolite of ISDN, does not undergo hepatic metabolism, achieves 100% bioavailability after oral dosing, and has a longer half-life of 4-5 hours 1
Nitroglycerin IV has a half-life of only several minutes, making it ideal for acute titration and the only nitrate formulated for intravenous use in the United States 1, 2
Evidence for Nitrate Use in Acute MI
The mortality benefit of nitrates in acute MI is modest at best:
The ISIS-4 trial (58,050 patients) compared controlled-release oral ISMN with placebo and found only a small, nonsignificant reduction in 35-day mortality (7.34% vs 7.54%) 1
Meta-analysis of all randomized trials shows a small but statistically significant relative mortality reduction of 5.5% ± 2.6% (p=0.003), representing approximately 4 lives saved per 1000 treated 1
The totality of evidence does not support routine long-term nitrate therapy in uncomplicated acute MI 1
Recommended Approach for Acute MI
Use IV nitroglycerin for the first 24-48 hours in patients with acute MI who have: 1
- Recurrent ischemia
- Congestive heart failure
- Hypertension requiring management
Transition to oral or topical nitrates only in patients with CHF and large transmural MIs 1
IV Nitroglycerin Protocol
- Starting dose: 5-10 mcg/min 2
- Titration: Increase by 5-10 mcg/min every 3-5 minutes based on blood pressure and symptom response 2
- Maximum dose: Typically 200 mcg/min 2
- Monitoring: Avoid systolic BP <90 mmHg or >30 mmHg below baseline 2
Comparative Onset of Action
When rapid action is required:
IV ISDN demonstrates significantly faster onset than IV ISMN in acute ischemic episodes, with perfusion defects reduced or resolved in 84.1% of patients at 3 minutes versus only 15.38% with ISMN 3
By 45 minutes, both agents show equivalent therapeutic effects with no statistically significant difference 3
ISDN should be preferred over ISMN when rapid onset is desired for acute ischemic episodes 3
Critical Safety Considerations
Exercise extreme caution in inferior wall MI because of frequent association with right ventricular infarction—these patients depend on adequate RV preload and can experience profound hypotension during nitrate administration 1, 4, 2
Contraindications include: 2, 5
- Sildenafil use within 24 hours
- Tadalafil use within 48 hours
- Initial systolic BP <90 mmHg
- Marked bradycardia or tachycardia
Hypotension management: Leg elevation, rapid fluid administration, and atropine are appropriate interventions 1, 4
Tolerance Prevention
Provide a nitrate-free interval of at least 10 hours to prevent tolerance development, which typically occurs after 24 hours of continuous therapy 4, 2
Oral Nitrate Dosing (When Indicated)
If transitioning to oral therapy for CHF or large transmural MI:
- ISDN: Start 20 mg three times daily, target 40 mg three times daily after 2-4 weeks if tolerated 2
- ISMN: Standard dosing is 20 mg twice daily with 12-24 hour duration of effect 4
Both ISDN and ISMN are available in sustained-release formulations 1