Isosorbide in Angina Management
Primary Role and Indication
Isosorbide dinitrate (ISDN) and isosorbide mononitrate (ISMN) are indicated exclusively for the prevention of angina pectoris, not for acute relief of anginal episodes. 1, 2 These agents function as symptomatic therapy only and provide no mortality or myocardial infarction reduction benefit. 3, 4
Formulation Selection and Dosing
Isosorbide Mononitrate (ISMN) - Preferred Agent
- ISMN is preferred over ISDN for long-term prophylaxis due to simpler once-daily dosing, more predictable pharmacokinetics, and superior patient compliance. 4
- Dose range: 60-240 mg once daily for sustained daytime antianginal effect without tolerance development. 3, 4
- Duration of action: 12-24 hours, making it suitable for once or twice daily dosing. 3
Isosorbide Dinitrate (ISDN) - Alternative Agent
- Dose range: 5-80 mg, 2-3 times daily with asymmetric dosing schedules (e.g., 7 AM and noon). 3, 4
- Requires more frequent dosing than ISMN. 4
Critical Tolerance Prevention Strategy
A mandatory 10-12 hour nitrate-free interval is required daily to prevent tolerance development for both ISDN and ISMN. 3, 4, 5
- Tolerance develops after 24 hours of continuous therapy and is dose and duration dependent. 5
- Without this nitrate-free interval, antianginal efficacy is lost. 3, 4
Hierarchical Treatment Algorithm
Step 1: Optimize Prognostic Therapy First
Before initiating isosorbide, ensure the following are optimized:
- Aspirin 75 mg daily for prognostic benefit. 6, 4
- Statin therapy regardless of baseline lipid levels. 6, 4
- Beta-blockers as first-line antianginal therapy (unless contraindicated). 6, 3
- Beta-blockers should be optimized to maximal tolerated dose before adding nitrates. 3, 4
Step 2: Add Isosorbide for Additional Symptom Control
- Isosorbide (ISDN or ISMN) may be added as second-line therapy when beta-blockers alone provide inadequate symptom control. 6, 3
- Alternatively, calcium channel blockers can be used instead of or in addition to nitrates. 6
Step 3: Consider Revascularization
- If symptoms remain uncontrolled despite optimal medical therapy including isosorbide, coronary arteriography should be undertaken with a view to revascularization. 6
Absolute Contraindications
Isosorbide is absolutely contraindicated in the following situations:
- Use within 24 hours of sildenafil or 48 hours of tadalafil due to risk of profound hypotension, myocardial infarction, and death. 3, 4
- Severe hypotension. 4
- Marked bradycardia or tachycardia. 4
- Right ventricular infarction. 4
- Angle-closure glaucoma. 4
- Severe anemia. 4
- ISMN is specifically contraindicated in cirrhotic patients older than 50 years due to increased mortality risk. 4
Common Side Effects and Management
- Dose-dependent headache is the most common side effect. 3, 5
- Postural hypotension, especially with overdosing or first use. 5
- Reflexogenic tachycardia leading to "paradoxical" angina with excessive dosing. 5
Special Considerations for Vasospastic Angina
For patients with confirmed vasospastic angina:
- Calcium channel blockers (e.g., verapamil 40 mg BID uptitrated) are first-line therapy. 6
- Long-acting nitrates (e.g., ISMN 10 mg BID) are second-line therapy, added to calcium channel blockers. 6
- This represents a specific exception where nitrates have a more prominent role in the treatment algorithm. 6
Critical Clinical Pitfall
Isosorbide formulations have onset of action that is NOT sufficiently rapid for aborting acute anginal episodes. 1, 2
- For acute angina relief, sublingual nitroglycerin (0.3-0.6 mg) or spray (0.4 mg) must be used instead. 4, 5
- An angina attack not responding to short-acting nitroglycerin should be regarded as possible myocardial infarction. 5