Can isosorbide (isosorbide mononitrate or isosorbide dinitrate) be used to treat hypertension?

Isosorbide for Hypertension: Limited Role Outside of Specific Heart Failure Scenarios

Isosorbide (mononitrate or dinitrate) is not recommended as a primary treatment for hypertension but has a specific role in African American patients with heart failure and hypertension.

Primary Role in Heart Failure with Hypertension

Isosorbide nitrates have a limited but important role in specific hypertension scenarios:

For African American Patients with Heart Failure and Hypertension

• The combination of hydralazine and isosorbide dinitrate is recommended for African American patients with NYHA class III-IV heart failure with reduced ejection fraction (HFrEF) who remain symptomatic despite standard therapy 1
• This combination should be added to the regimen of diuretic, ACE inhibitor/ARB, and beta-blocker 1
• The fixed-dose combination has shown significant mortality benefit in this population, with the A-HeFT trial demonstrating reduction in mortality from 10.2% to 6.2% 1

For Patients Intolerant to First-Line Agents

• In patients with HFrEF who cannot tolerate ACE inhibitors or ARBs due to drug intolerance, hypotension, or renal insufficiency, the combination of hydralazine and isosorbide dinitrate might be considered 1
• This is a Class IIa recommendation with Level of Evidence B 1

Important Limitations and Precautions

Not for Primary Hypertension

• Nitrate tolerance has limited the ability of long-term nitrates alone to be effective as antihypertensive agents 1
• Monotherapy with hydralazine in ischemic heart disease is not recommended due to lack of randomized trial evidence and concerns that it may provoke angina 1

Proper Administration to Avoid Tolerance

• If using the fixed-dose combination, start with 1 tablet containing 37.5 mg hydralazine and 20 mg isosorbide dinitrate three times daily 1
• Can be increased to 2 tablets three times daily (total daily dose: 225 mg hydralazine and 120 mg isosorbide dinitrate) 1
• When used separately, both drugs should be administered at least 3 times daily 1
• A nitrate-free interval of at least 10 hours may minimize tolerance 1

Common Side Effects and Adherence Issues

• Headache and hypotension are the most common side effects 1
• Poor adherence is common due to:
  • Large number of tablets required
  • Frequent administration (three times daily)
  • High incidence of adverse reactions including headaches, dizziness, and gastrointestinal complaints 1

Evidence from Research Studies

Some small studies have shown potential benefits of isosorbide in specific hypertension scenarios:

• In maintenance hemodialysis patients with hypertension, sustained-release isosorbide mononitrate (30-120 mg daily) effectively controlled blood pressure and decreased left ventricular hypertrophy 2
• Isosorbide dinitrate aerosol has shown effectiveness in hypertensive crises, reducing mean arterial pressure from 136.6±8 to 109.5±7 mmHg within 30 minutes 3
• Extended-release isosorbide mononitrate (60-120 mg once daily) has demonstrated long-term effectiveness in systolic hypertension as adjunct therapy 4

First-Line Treatments for Hypertension in Heart Failure

For patients with hypertension and heart failure, the following medications should be prioritized before considering isosorbide:

1. ACE inhibitors or ARBs
2. Beta-blockers (carvedilol, metoprolol succinate, bisoprolol, or nebivolol)
3. Aldosterone receptor antagonists
4. Thiazide or thiazide-type diuretics 1

Conclusion

While isosorbide has some utility in specific scenarios, particularly in combination with hydralazine for African American patients with heart failure, it is not a first-line agent for the general treatment of hypertension. Its use should be reserved for specific indications as outlined in current guidelines.