From the Guidelines
Isosorbide dinitrate can cause bradycardia as a side effect, though it is not among the most common adverse reactions. Isosorbide dinitrate is a nitrate medication primarily used to treat and prevent angina by dilating blood vessels. When blood vessels dilate, blood pressure drops, which can trigger a reflex tachycardia. However, in some patients, particularly those with underlying conduction system disease or those taking other medications that affect heart rate, the medication can paradoxically cause bradycardia. This occurs through complex mechanisms involving baroreceptor reflexes and direct effects on cardiac conduction.
Key Points to Consider
- Patients taking isosorbide dinitrate should be monitored for symptoms of bradycardia such as dizziness, fatigue, or syncope, especially when starting therapy or increasing doses.
- The risk increases when combined with other medications that slow heart rate, such as beta-blockers or calcium channel blockers.
- If bradycardia develops, dose adjustment or medication change may be necessary under medical supervision, as noted in guidelines for managing heart failure and other cardiovascular conditions 1.
Management of Bradycardia
In cases where bradycardia is suspected to be caused by isosorbide dinitrate, management strategies may include adjusting the dose of the medication or switching to an alternative treatment. For symptomatic bradycardia, atropine remains a first-line treatment option, with a recommended dose of 0.5 mg IV every 3 to 5 minutes to a maximum total dose of 3 mg 1.
Clinical Considerations
It's essential to weigh the benefits of isosorbide dinitrate in managing conditions like heart failure against the potential risks, including bradycardia, and to closely monitor patients for any adverse effects. The combination of isosorbide dinitrate and hydralazine is specifically recommended for African American patients with heart failure who remain symptomatic despite optimal medical therapy, highlighting the importance of tailored treatment approaches 1.
From the FDA Drug Label
Hypotension induced by isosorbide dinitrate may be accompanied by paradoxical bradycardia and increased angina pectoris ...heart block and bradycardia...
Isosorbide dinitrate may cause bradycardia, as it can induce hypotension which may be accompanied by paradoxical bradycardia. Additionally, bradycardia is listed as a potential effect of isosorbide dinitrate overdose 2, 2.
From the Research
Isosorbide Dinitrate and Bradycardia
- Isosorbide dinitrate can cause bradycardia in some patients, as seen in a study where 14 patients developed severe systemic arterial hypotension, associated with absolute or relative bradycardia, within 30 minutes of receiving the drug 3.
- The mechanism producing bradycardia, hypotension, and lipothymia after nitrates administration is considered to be a vagally mediated reflex possibly elicited by a fall in venous return 3.
- Another study found that isosorbide dinitrate decreased filling pressure and improved forward cardiac output in some patients with congestive heart failure, but large doses may decrease cardiac output in a subset of patients who have a lower systemic vascular resistance and a larger more compliant ventricle 4.
- However, not all studies found a significant effect of isosorbide dinitrate on heart rate, as one study found that the baseline heart rate of 105 beats/min was not significantly changed after administration of isosorbide dinitrate 5.
- In contrast, another study found that swallowed isosorbide dinitrate increased heart rate in patients with coronary artery disease, with the changes being more striking with the patients standing than with them supine 6.
- A more recent study found that isosorbide dinitrate, with or without hydralazine, did not reduce wave reflections, left ventricular hypertrophy, or myocardial fibrosis in patients with heart failure with preserved ejection fraction, and was poorly tolerated 7.