Is isosorbide dinitrate (Isordil) effective for treating hypertension?

From the Guidelines

Isosorbide dinitrate is not typically recommended as a first-line treatment for hypertension. It is primarily used to treat and prevent angina (chest pain) and can be used in heart failure management, but it is not FDA-approved specifically for hypertension. The medication works by relaxing blood vessels through the release of nitric oxide, which can temporarily lower blood pressure, but it develops tolerance quickly when used continuously, making it ineffective for long-term blood pressure control.

Key Points to Consider

• For hypertension management, first-line medications include thiazide diuretics, calcium channel blockers, ACE inhibitors, or angiotensin II receptor blockers, which have better evidence for long-term blood pressure control and reduction of cardiovascular events 1.
• If isosorbide dinitrate is needed for angina in a patient with hypertension, it should be used alongside proper antihypertensive medications.
• The typical dosage for angina is 5-40 mg orally 2-3 times daily for the immediate-release form, or 40-80 mg daily for extended-release preparations, but dosing should be individualized.
• Side effects may include headache, dizziness, and hypotension, especially when starting therapy.

Special Considerations

• In certain cases, such as African American patients with heart failure and reduced ejection fraction, the addition of hydralazine and isosorbide dinitrate to standard therapy may be beneficial 1.
• However, this is not a recommendation for the general treatment of hypertension, and other factors such as comorbidities and individual patient needs should be considered.

Evidence-Based Recommendations

• The American Heart Association recommends controlling hypertension in accordance with contemporary guidelines to lower the risk of developing heart failure 1.
• Patients with heart failure with reduced ejection fraction should be treated with guideline-directed medical therapy, including diuretics, ACE inhibitors or ARBs, β-blockers, and aldosterone receptor antagonists, which have been proven to improve outcomes for patients with heart failure and can lower blood pressure in hypertensive patients with heart failure with reduced ejection fraction 1.

From the Research

Isosorbide Dinitrate for Hypertension

• Isosorbide dinitrate (ISDN) has been used in combination with other antianginal agents to treat angina pectoris, hypertension, and congestive heart failure 2.
• The addition of ISDN to other standard and proven antianginal agents, including calcium antagonists, may be a fruitful area for further clinical research benefiting patients with these conditions 2.
• However, the use of ISDN for hypertension is not well-established, and its efficacy and safety in this context are not clearly defined in the provided studies.
• One study suggests that ISDN may be used in combination with hydralazine to improve survival in patients with heart failure, but this combination therapy is inferior to ACE inhibitors 3.
• Another study found that the fixed-dose combination of ISDN and hydralazine was effective in reducing mortality and morbidity in African-American patients with heart failure, regardless of whether they were taking ACE inhibitors or beta-blockers 4.
• The importance of circadian rhythms on drug response in hypertension and coronary heart disease has been highlighted, and it is suggested that anti-hypertensive drugs should be given in the early morning for hypertensive dippers, whereas in non-dippers, it may be necessary to add an evening dose or use a single evening dose 5.
• ISDN has been shown to provide more rapid relief of pain than sublingual tablets in elderly patients with angina pectoris when administered as an oral spray 6.

Mechanisms and Effects

• The exact mechanism responsible for in-vitro tolerance to nitrates, including ISDN, remains unknown, but several mechanisms have been proposed, including depletion of sulfhydryl groups and reduced biotransformation of nitrates to NO or nitrosothiols 3.
• In-vivo tolerance of the beneficial effects of nitrates on hemodynamics, myocardial ischemia, and exercise performance develops rapidly, and the use of agents to counteract these mechanisms has produced conflicting results 3.
• The development of venous tolerance and not arterial tolerance may be responsible for the attenuation of nitrate effects during long-term nitrate therapy, but this remains to be proven 3.

Clinical Implications

• The use of ISDN in combination with other agents, such as hydralazine, may be beneficial in certain patient populations, such as those with heart failure 4.
• The timing of anti-hypertensive drug administration may be important, with morning dosing potentially being more effective for hypertensive dippers and evening dosing potentially being more effective for non-dippers 5.
• ISDN oral spray may be a useful alternative to sublingual tablets for the treatment of angina pectoris in elderly patients, providing more rapid relief of pain 6.