Does hydralazine (Hydralazine) cause bradycardia (abnormally slow heart rate)?

From the Guidelines

Hydralazine does not typically cause bradycardia, but rather reflex tachycardia, as it dilates blood vessels and reduces blood pressure, triggering a compensatory increase in heart rate. According to the 2018 guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1, hydralazine is a vasodilator medication that is used to treat hypertensive emergencies, with an initial dose of 10 mg via slow IV infusion, and its effects on blood pressure begin to decrease within 10-30 minutes. The guideline does not mention bradycardia as a common side effect of hydralazine, but rather notes that it can cause reflex tachycardia. Additionally, the 2009 focused update on the diagnosis and management of heart failure in adults 1 recommends the combination of hydralazine and nitrates to improve outcomes for patients with moderate-severe symptoms on optimal therapy with ACE inhibitors, beta blockers, and diuretics, but does not mention bradycardia as a side effect of this combination.

Some key points to consider when using hydralazine include:

• Typical dosing ranges from 10-75 mg four times daily for hypertension or 10-75 mg three to four times daily for heart failure
• Hydralazine is often prescribed alongside beta-blockers or other heart rate-controlling medications to counteract the reflex tachycardia effect
• If a patient experiences an unusually slow heart rate while taking hydralazine, it's more likely due to another medication or condition rather than the hydralazine itself, and they should consult their healthcare provider promptly.

It's also important to note that other medications, such as beta-blockers, can cause bradycardia, and patients taking these medications should be closely monitored for this side effect 1. Overall, hydralazine is not typically associated with bradycardia, and its use is generally focused on treating hypertension and heart failure, rather than causing slow heart rates.

From the FDA Drug Label

Although the precise mechanism of action of hydrALAZINE is not fully understood, the major effects are on the cardiovascular system. HydrALAZINE apparently lowers blood pressure by exerting a peripheral vasodilating effect through a direct relaxation of vascular smooth muscle HydrALAZINE, by altering cellular calcium metabolism, interferes with the calcium movements within the vascular smooth muscle that are responsible for initiating or maintaining the contractile state The peripheral vasodilating effect of hydrALAZINE results in decreased arterial blood pressure (diastolic more than systolic); decreased peripheral vascular resistance; and an increased heart rate, stroke volume, and cardiac output.

• Hydralazine is not associated with bradycardia.
• In fact, the drug label states that hydralazine results in an increased heart rate. 2

From the Research

Hydralazine and Bradycardia

• Hydralazine is generally recognized to produce hypotension accompanied by baroreflex-mediated tachycardia, but in some cases, it can cause bradycardia, a paradoxical response that has not been fully explained 3.
• A study in conscious normotensive and hypertensive rats found that hydralazine can induce hypotension accompanied by either tachycardia, unchanged heart rate, or bradycardia, suggesting that the drug can initiate two reflexes with opposite effects on heart rate: the arterial baroreflex producing tachycardia and a cardiac mechanoreceptor reflex producing bradycardia 4.
• Another study found that hydralazine produced hypotension and tachycardia in intact rats, but hypotension and bradycardia in sino-aortic deafferented (SAD) animals, suggesting that the suppression of the arterial baroreflex by SAD can lead to a bradycardiac response to hydralazine 3.
• However, a clinical study found that hydralazine was used to increase heart rate in patients with symptomatic sinus bradycardia, and it ameliorated symptoms and produced a 20% or greater increase in heart rate in some patients 5.
• Other studies have reported that hydralazine may cause reflex tachycardia as an adverse effect, but its effect on clinical outcomes, including bradycardia, remains uncertain 6, 7.

Mechanisms and Effects

• The exact mechanisms of hydralazine-induced bradycardia are not fully understood, but it is thought to involve the activation of a vagal cardiodepressant reflex originating in the heart 3.
• The effects of hydralazine on heart rate can vary depending on the individual and the specific conditions, and more research is needed to fully understand its effects on cardiovascular outcomes 4, 6, 7.
• Hydralazine may reduce blood pressure when compared to placebo in patients with primary hypertension, but its effect on clinical outcomes, including bradycardia, remains uncertain 6, 7.