Isosorbide Mononitrate Uses
Isosorbide mononitrate is indicated for the prevention of angina pectoris due to coronary artery disease, providing symptomatic relief by reducing myocardial oxygen demand through vasodilation, but it does not improve mortality or prevent cardiovascular events. 1
Primary Indication
- Isosorbide mononitrate is FDA-approved specifically for prevention of angina pectoris in patients with coronary artery disease. 1
- The onset of action is not sufficiently rapid to abort acute anginal episodes—sublingual nitroglycerin should be used for acute attacks instead. 1
Mechanism of Action
Isosorbide mononitrate works through multiple hemodynamic effects that reduce cardiac workload:
- Venodilation reduces preload by decreasing venous return to the heart, lowering ventricular volume and myocardial wall tension. 2
- Arterial vasodilation reduces afterload through peripheral arterial dilation. 2
- At higher doses, it dilates coronary arteries, prevents coronary spasm, and improves subendocardial blood flow to ischemic areas. 3
- The net effect is decreased cardiac work and lower myocardial oxygen requirements. 2
Clinical Efficacy and Limitations
Critical limitation: Nitrates provide symptomatic relief only and offer no prognostic benefit—they do not reduce myocardial infarction or death. 3, 4
- Meta-analyses show no differences in symptom relief or exercise parameters between nitrates and other antianginal agents. 3
- Nitrates are effective for patients with macrovascular or microvascular angina who have overlapping coronary spasm. 3
- However, nitrates have disappointing results in pure microvascular angina because small arterioles are nitrate-resistant. 3
Optimal Dosing Strategy
The most effective regimen is 20 mg twice daily with a nitrate-free interval of at least 10-14 hours to prevent tolerance. 4, 5
- Standard dosing: 20 mg twice daily (morning and midday) or 60-240 mg once daily for sustained-release formulations. 4
- Tolerance develops rapidly with continuous 24-hour exposure—a nitrate-free interval of 10-14 hours is essential. 4, 5
- Higher doses (50-100 mg once daily) lose efficacy after one week due to tolerance development. 6, 7
Combination Therapy
Combining isosorbide mononitrate with beta-blockers provides synergistic anti-ischemic effects by blocking reflex tachycardia. 3
- Nitrates alone can cause reflex sympathetic activation with increased heart rate and contractility. 3
- Beta-blockers should be optimized first before adding nitrates for additional symptom control. 4
Critical Contraindications
Absolute contraindication: Do not use within 24 hours of sildenafil or 48 hours of tadalafil due to risk of profound hypotension, myocardial infarction, and death. 2, 4, 5
- Use with extreme caution in right ventricular infarction, as these patients depend on adequate RV preload to maintain cardiac output. 2, 5
- Patients with inferior wall MI with RV involvement risk profound hypotension. 2, 5
Common Side Effects
- Headache is the most frequent side effect but usually improves with continued therapy. 2, 8
- Hypotension may cause reflex tachycardia and paradoxically worsen myocardial ischemia. 2
- Dizziness related to blood pressure changes is common. 2
- Hypotension can be managed by dose adjustment, leg elevation, fluid administration, or atropine if severe. 2
Special Populations
- African American patients with heart failure may benefit from combination therapy with hydralazine and isosorbide dinitrate (37.5 mg/20 mg three times daily). 5
- In acute myocardial infarction, isosorbide mononitrate 20 mg three times daily can be safely used to prevent post-infarction angina without hemodynamic deterioration. 9