What is the role of Hydralazine in treating hypertension?

From the Guidelines

Hydralazine is not a first-line treatment for hypertension but is often used in specific clinical scenarios, such as hypertensive emergencies, pregnancy, or in combination therapy when other medications are insufficient. It works primarily by relaxing the smooth muscle in arterial walls, causing blood vessels to dilate, which reduces peripheral resistance and lowers blood pressure 1. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline, hydralazine can be used intravenously for hypertensive emergencies, with an initial dose of 10 mg via slow IV infusion, repeated every 4-6 hours as needed 1.

The medication is particularly useful in patients with renal impairment and has historically been important in managing hypertension in pregnancy and heart failure. However, long-term use requires monitoring for potential development of drug-induced lupus-like syndrome, which can occur with higher doses used for extended periods. In African American patients with advanced heart failure, the combination of hydralazine and isosorbide dinitrate has been shown to provide additional benefit, as demonstrated in the African-American Heart Failure Trial (A-heFT) 1.

Key points to consider when using hydralazine include:

• It is not a first-line treatment for hypertension
• It is useful in specific clinical scenarios, such as hypertensive emergencies or pregnancy
• It can be used in combination therapy when other medications are insufficient
• Long-term use requires monitoring for potential side effects, such as drug-induced lupus-like syndrome
• The combination of hydralazine and isosorbide dinitrate can provide additional benefit in African American patients with advanced heart failure.

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 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.

The role of Hydralazine in treating hypertension is to lower blood pressure by exerting a peripheral vasodilating effect, which results in:

• Decreased arterial blood pressure
• Decreased peripheral vascular resistance
• Increased heart rate, stroke volume, and cardiac output 2

From the Research

Role of Hydralazine in Treating Hypertension

• Hydralazine is a direct-acting vasodilator that has been used for the treatment of hypertension since the 1950s 3.
• It is still widely used in developing countries due to its lower cost, although it has largely been replaced by newer antihypertensive drugs with more acceptable tolerability profiles 3.
• The evidence for the use of hydralazine in treating hypertension is limited, with no randomized controlled trials comparing hydralazine to placebo for inclusion in a review 3.
• However, hydralazine may reduce blood pressure when compared to placebo in patients with primary hypertension, although this data is based on before and after studies, not RCTs 3.

Clinical Use of Hydralazine

• Hydralazine is often used in combination with nitrates for the treatment of heart failure with reduced ejection fraction (HFREF) 4.
• This combination has been shown to improve survival in patients with HFREF, particularly in Black patients 4.
• Hydralazine may also be used as a bridging therapy for patients with contraindications to the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers, and sacubitril-valsartan 4.
• In hospitalized medicine patients, hydralazine is frequently prescribed for acute blood pressure lowering, often with administration thresholds less than what are used to define acute severe hypertension 5.

Adverse Effects and Limitations

• Hydralazine has been associated with several adverse effects, including reflex tachycardia, hemolytic anemia, vasculitis, glomerulonephritis, and a lupus-like syndrome 3.
• The use of hydralazine is often limited by its side effects and the availability of newer antihypertensive drugs with more favorable tolerability profiles 3.
• Despite its potential benefits, hydralazine is not typically recommended as a first-line therapy for hypertension, with lifestyle modification and other antihypertensive medications preferred 6.