What is the use of Hydralazine (Apresoline)?

From the Guidelines

Hydralazine should be used with caution and only when necessary, as its unpredictability of response and prolonged duration of action do not make it a desirable first-line agent for acute treatment in most patients. According to the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults 1, hydralazine is a direct-acting vasodilator that can be used to treat hypertensive emergencies, with an initial dose of 10 mg via slow IV infusion, which can be repeated every 4-6 hours as needed. The blood pressure begins to decrease within 10-30 minutes, and the fall lasts 2-4 hours. However, its use is limited by its unpredictability of response and prolonged duration of action.

In certain patient populations, such as African American patients with heart failure, hydralazine may be particularly useful, especially when combined with nitrates like isosorbide dinitrate, as shown in the African-American Heart Failure Trial (A-heFT) 1. This combination has been shown to provide additional benefit in these patients, reducing mortality rates and improving symptoms of heart failure.

It is essential to monitor patients on long-term hydralazine therapy for potential side effects, including a lupus-like syndrome, which can occur particularly at higher doses. Patients should take hydralazine consistently with meals to improve absorption and minimize side effects, and should report any unexplained joint pain, fever, or rash, which could indicate the development of drug-induced lupus.

In summary, while hydralazine can be a useful medication in certain situations, its use should be approached with caution, and alternative treatments should be considered first, due to its potential limitations and side effects. The most recent and highest quality study, the 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline 1, provides the best guidance on the use of hydralazine in clinical practice.

Key points to consider when using hydralazine include:

• Initial dose: 10 mg via slow IV infusion
• Repeat dose: every 4-6 hours as needed
• Onset of action: 10-30 minutes
• Duration of action: 2-4 hours
• Potential side effects: lupus-like syndrome, headache, dizziness, flushing, palpitations, and nasal congestion
• Special considerations: African American patients with heart failure, pregnancy-related hypertension.

From the FDA Drug Label

PRECAUTIONS General Myocardial stimulation produced by hydrALAZINE can cause anginal attacks and ECG changes of myocardial ischemia. The drug has been implicated in the production of myocardial infarction. It must, therefore, be used with caution in patients with suspected coronary artery disease The “hyperdynamic” circulation caused by hydrALAZINE may accentuate specific cardiovascular inadequacies. For example, hydrALAZINE may increase pulmonary artery pressure in patients with mitral valvular disease. In hypertensive patients with normal kidneys who are treated with hydrALAZINE, there is evidence of increased renal blood flow and a maintenance of glomerular filtration rate. However, as with any antihypertensive agent, hydrALAZINE should be used with caution in patients with advanced renal damage.

The main precautions for Hydralazine are:

• Cardiovascular: use with caution in patients with suspected coronary artery disease, as it may cause anginal attacks, ECG changes, and myocardial infarction.
• Cardiovascular inadequacies: may accentuate specific cardiovascular inadequacies, such as increasing pulmonary artery pressure in patients with mitral valvular disease.
• Renal damage: use with caution in patients with advanced renal damage, although it may increase renal blood flow and maintain glomerular filtration rate in patients with normal kidneys 2.

From the Research

Hydralazine Overview

• 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 3
• Hydralazine and nitrates combination has been shown to improve survival of patients with heart failure with reduced ejection fraction (HFREF) 4

Clinical Uses

• Hydralazine is used in the treatment of heart failure with reduced ejection fraction, particularly in combination with nitrates 4, 5
• It is also used for the treatment of hypertension, although its use has largely been replaced by newer antihypertensive drugs with more acceptable tolerability profiles 3
• As-needed oral hydralazine is frequently prescribed for acute blood pressure lowering in hospitalized patients 6

Efficacy and Safety

• The combination of hydralazine and nitrates has been shown to reduce mortality in patients with HFREF 4, 5
• However, when compared to angiotensin converting enzyme inhibitors (ACEIs), combination therapy was associated with higher all-cause mortality and cardiovascular mortality 5
• Hydralazine alone has been shown to have little evidence to support its use in CHF, and may be inferior to ACEI 5
• Common adverse effects of hydralazine include reflex tachycardia, hemolytic anemia, vasculitis, glomerulonephritis, and a lupus-like syndrome 3

Guidelines and Recommendations

• The European Society of Cardiology (ESC) Guidelines and the guidelines of the National Institute for Health and Care Excellence (NICE) suggest that the combination of hydralazine and nitrates may have a potential use in patients with contraindications to the use of ACEi, angiotensin receptor blockers, and sacubitril-valsartan 4
• The use of hydralazine and nitrates in the treatment of HFREF is recommended, particularly in Black patients with HFREF when added to their standard therapy 4