What is isosorbide dinitrate used for?

Isosorbide Dinitrate: Clinical Uses and Applications

Isosorbide dinitrate is primarily used for the treatment of angina pectoris due to coronary artery disease and as part of combination therapy with hydralazine for heart failure with reduced ejection fraction, particularly in African American patients.

Primary Indications

Angina Pectoris

• FDA-approved for prevention and treatment of angina pectoris due to coronary artery disease 1, 2
• Works through vasodilation, reducing cardiac preload and myocardial oxygen requirements 3
• Improves the ratio of myocardial oxygen demand to supply, alleviating myocardial ischemia 3
• Sublingual formulation can be used to abort an acute anginal episode, though it is not the first-line agent (nitroglycerin is preferred due to faster onset) 1

Heart Failure with Reduced Ejection Fraction (HFrEF)

• Used in combination with hydralazine, particularly for:
  • African American patients with NYHA class III-IV HFrEF who remain symptomatic despite standard therapy 3, 4
  • Patients who cannot tolerate ACE inhibitors or ARBs due to hypotension or renal insufficiency 3
• The combination has been shown to reduce mortality in African American patients with HFrEF 3, 4

Mechanism of Action

• Causes vasodilation of both venous and arterial vessels
• Reduces preload (venous dilation) and afterload (arterial dilation)
• Improves coronary blood flow by:
  • Dilating coronary arteries 3
  • Reversing vasoconstriction of small coronary arteries distal to obstructions 3
  • Dilating coronary collateral vessels 3
  • Reducing platelet aggregation 3

Dosing Considerations

• For angina prevention: Oral tablets taken 15 minutes before anticipated activity 1
• For heart failure (in combination with hydralazine):
  • Initial dose: 20 mg isosorbide dinitrate with 37.5 mg hydralazine three times daily 4
  • Can be increased to 40 mg isosorbide dinitrate with 75 mg hydralazine three times daily 4
• A nitrate-free interval of at least 10 hours daily is required to prevent tolerance 4, 5

Important Clinical Considerations

Nitrate Tolerance

• Develops rapidly with continuous 24-hour plasma levels 1, 5, 6
• Intermittent dosing with a daily nitrate-free interval (preferably >10-12 hours) is essential 5, 6
• Once-daily dosing of sustained-release formulations can help prevent tolerance 5

Adverse Effects

• Headache (most common side effect) 3, 4
• Hypotension, potentially causing reflex tachycardia 3, 4
• May aggravate hypoxemia by increasing ventilation-perfusion mismatch 3
• Gastrointestinal complaints 3

Special Precautions

• Use cautiously in patients with inferior wall MI with right ventricular involvement due to risk of profound hypotension 3
• Poor adherence is common due to frequent dosing requirements and side effects 3, 4
• Should not replace ACE inhibitors/ARBs in patients who can tolerate them 3

Therapeutic Hierarchy in Heart Failure

For patients with HFrEF, isosorbide dinitrate with hydralazine should be considered after or in addition to:

1. ACE inhibitors/ARBs/ARNi
2. Beta-blockers
3. Mineralocorticoid receptor antagonists
4. SGLT2 inhibitors 3

The combination is particularly beneficial for African American patients with HFrEF and should be added to standard therapy when patients remain symptomatic 3, 4.