Is isosorbide (isosorbide dinitrate) effective for treating acute decompensated heart failure?

From the Guidelines

Isosorbide dinitrate can be effective for treating acute decompensated heart failure, particularly when combined with hydralazine, as evidenced by the 2022 AHA/ACC/HFSA guideline 1. For acute management, intravenous nitroglycerin is typically preferred over oral isosorbide dinitrate due to its faster onset and easier titration. When using oral isosorbide dinitrate in acute settings, dosing typically starts at 10-20 mg every 6-8 hours, which can be titrated up as needed and tolerated. The combination of isosorbide dinitrate with hydralazine (typically 10-40 mg isosorbide with 25-75 mg hydralazine three to four times daily) is particularly beneficial in African American patients with heart failure, as shown in a post hoc retrospective analysis of vasodilator trials 1. Isosorbide dinitrate works as a vasodilator that reduces preload by dilating venous vessels, decreasing venous return to the heart, and consequently reducing pulmonary congestion. It also provides some afterload reduction through arterial dilation. Common side effects include headache, hypotension, and dizziness. Nitrate tolerance can develop with continuous use, so a nitrate-free interval (often overnight) is recommended for long-term therapy. Blood pressure should be monitored closely during administration, and the medication should be used cautiously in patients with hypotension or those taking phosphodiesterase inhibitors like sildenafil. Key benefits of isosorbide dinitrate in acute decompensated heart failure include:

• Reduction in mortality when combined with hydralazine in certain patient populations 1
• Improvement in symptoms and reduction in hospitalizations in patients who cannot tolerate ACE inhibitors or ARBs 1
• Particular efficacy in African American patients with heart failure 1

From the FDA Drug Label

The benefits of immediate-release oral isosorbide dinitrate in patients with acute myocardial infarction or congestive heart failure have not been established. If one elects to use isosorbide dinitrate in these conditions, careful clinical or hemodynamic monitoring must be used to avoid the hazards of hypotension and tachycardia. Key Points:

• The effectiveness of isosorbide dinitrate for treating acute decompensated heart failure is not established.
• If used in this setting, careful monitoring is required to avoid hypotension and tachycardia.
• The drug label does not recommend the use of oral isosorbide dinitrate in acute myocardial infarction or congestive heart failure due to the difficulty in rapidly terminating its effects 2, 2.

From the Research

Efficacy of Isosorbide for Acute Decompensated Heart Failure

• Isosorbide dinitrate is a vasodilator that has been used in the treatment of heart failure, including acute decompensated heart failure 3, 4, 5, 6, 7.
• The combination of hydralazine and isosorbide dinitrate has been shown to be effective in improving symptoms, exercise capacity, and quality of life in patients with heart failure with reduced ejection fraction 3.
• Isosorbide dinitrate has been found to improve hemodynamic parameters, reduce blood pressure, and increase coronary flow in patients with acute heart failure 4.
• However, the use of isosorbide dinitrate in acute decompensated heart failure is not without risks, and patients should be closely monitored for potential adverse effects such as hypotension 4, 6.

Mechanism of Action

• Isosorbide dinitrate works by producing venodilation, which reduces preload and decreases left ventricular end-diastolic diameter and the volume of mitral regurgitation 3, 5.
• It also has arterial vasodilating properties, which decrease afterload and reduce left atrial and left ventricular wall tension 3.
• The combination of hydralazine and isosorbide dinitrate has been shown to have antioxidant properties and improve NO bioavailability, which can beneficially affect endothelial dysfunction 3.

Clinical Outcomes

• The addition of isosorbide dinitrate and hydralazine to standard neurohormonal blockade has been associated with improved hemodynamic profiles and clinical outcomes in patients with advanced decompensated heart failure 7.
• Isosorbide dinitrate has been found to reduce mortality and heart failure rehospitalization in patients with acute decompensated heart failure, regardless of race 7.
• However, the evidence for the use of isosorbide dinitrate in acute decompensated heart failure is limited, and further studies are needed to fully understand its effects 4, 7.