In patients with normal renal function but elevated Liver Function Tests (LFTs), which is safer to treat hypertension - Hydrochlorothiazide (HCTZ) or Metoprolol?

From the Guidelines

Metoprolol is generally safer than hydrochlorothiazide (HCTZ) for treating hypertension in patients with good renal function but elevated liver function tests (LFTs). 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, beta blockers like metoprolol are not recommended as first-line agents unless the patient has ischemic heart disease (IHD) or heart failure (HF), but they can be considered in patients with certain comorbidities. Metoprolol, a beta-blocker, undergoes significant metabolism in the liver but has a favorable safety profile even with mild to moderate hepatic impairment.

The standard dosing for metoprolol tartrate starts at 25-50 mg twice daily, which can be titrated up to 100 mg twice daily as needed, while metoprolol succinate (extended-release) typically starts at 25-50 mg once daily. HCTZ, a thiazide diuretic, though primarily eliminated by the kidneys, can occasionally cause idiosyncratic hepatotoxicity and may exacerbate electrolyte abnormalities that could be problematic in liver disease. Additionally, patients with liver dysfunction may have reduced albumin levels, affecting protein binding of HCTZ and potentially increasing its free concentration.

When using metoprolol in these patients, it's advisable to start at a lower dose and monitor for signs of beta-blockade such as bradycardia or hypotension. Regular monitoring of LFTs is also recommended to ensure the medication isn't further compromising hepatic function. If liver impairment is severe, consultation with a hepatologist and consideration of alternative antihypertensives like certain calcium channel blockers might be warranted. Key considerations for metoprolol use include:

• Starting at a lower dose to minimize potential side effects
• Monitoring for signs of beta-blockade
• Regular LFT monitoring to assess hepatic function
• Potential consultation with a hepatologist for severe liver impairment.

From the FDA Drug Label

Metabolism Metoprolol is primarily metabolized by CYP2D6. Hepatic Impairment Since the drug is primarily eliminated by hepatic metabolism, hepatic impairment may impact the pharmacokinetics of metoprolol. The elimination half-life of metoprolol is considerably prolonged, depending on severity (up to 7. 2 h).

In patients with good renal function but increased LFTs, metoprolol may not be the safest option due to its hepatic metabolism.

• Hepatic impairment may impact the pharmacokinetics of metoprolol, leading to a prolonged elimination half-life.
• This could potentially increase the risk of adverse effects, particularly in patients with pre-existing liver function abnormalities. Given the information available, HCTZ may be a safer option for treating high blood pressure in this patient population, as it is not primarily metabolized by the liver 2.

From the Research

Comparison of HCTZ and Metoprolol in Patients with High BP and Increased LFTs

• The safety of HCTZ (hydrochlorothiazide) and metoprolol in patients with good renal function but increased liver function tests (LFTs) is a concern, as both medications are metabolized by the liver 3.
• HCTZ is a thiazide diuretic, which can be used in combination therapy for the treatment of hypertension, but its use in patients with abnormal LFTs requires careful consideration 4.
• Metoprolol is a beta blocker, which can be used to treat hypertension, especially in patients with heart failure, but its metabolism is affected by liver function 5.
• There is limited evidence directly comparing the safety of HCTZ and metoprolol in patients with increased LFTs, but it is known that patients with abnormal LFTs are at higher risk of adverse outcomes, such as increased 30-day mortality or HF rehospitalization 5.
• The evaluation of abnormal LFTs in hospitalized patients is typically more urgent than in the outpatient setting, and requires a step-by-step approach to determine the etiology and severity of liver dysfunction 6.
• Laboratory values, including LFTs, correlate poorly with liver disease, and normal or near-normal laboratory findings may be seen in asymptomatic patients with chronic liver disease 7.

Key Considerations

• The use of HCTZ and metoprolol in patients with increased LFTs requires careful consideration of the potential risks and benefits.
• Patients with abnormal LFTs are at higher risk of adverse outcomes, and require close monitoring and adjustment of medication as needed.
• The evaluation of abnormal LFTs should be done in a step-by-step approach to determine the etiology and severity of liver dysfunction.
• Laboratory values, including LFTs, should be interpreted with caution, as they may not accurately reflect the severity of liver disease.