Which is more likely to exacerbate orthostatic hypotension, Losartan (Angiotensin II Receptor Antagonist) or Hydrochlorothiazide (HCTZ) (Thiazide Diuretic)?

From the Guidelines

Losartan is generally less likely to cause orthostatic hypotension than hydrochlorothiazide (HCTZ). While both medications can lower blood pressure and potentially cause orthostatic hypotension, HCTZ as a diuretic directly reduces blood volume, which can more readily lead to this side effect 1. HCTZ works by increasing urination and reducing fluid volume in the body, which can cause more pronounced drops in blood pressure upon standing, especially in elderly patients or those who are dehydrated.

Key Differences Between Losartan and HCTZ

• Losartan, an angiotensin II receptor blocker (ARB), works by relaxing blood vessels but typically causes less orthostatic hypotension because it doesn't directly reduce blood volume 1.
• The mechanism of action of losartan is less likely to cause dehydration and significant changes in blood volume, reducing the risk of orthostatic hypotension.
• HCTZ, on the other hand, can lead to hypokalemia and hyponatremia, further increasing the risk of orthostatic hypotension, as noted in the guideline for the management of high blood pressure in adults 1.

Recommendations for Patients

• Patients taking either medication should stay well-hydrated, avoid standing up too quickly, and report dizziness or lightheadedness to their healthcare provider, who may need to adjust dosing or timing of the medication.
• Healthcare providers should closely monitor patients, especially the elderly or those with a history of dehydration, for signs of orthostatic hypotension when prescribing HCTZ.
• The choice between losartan and HCTZ should be based on individual patient factors, including the presence of conditions that may increase the risk of orthostatic hypotension, such as dehydration or autonomic dysfunction.

From the FDA Drug Label

When given concurrently the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, or narcotics - potentiation of orthostatic hypotension may occur. In patients with an activated renin-angiotensin system, such as volume- or salt-depleted patients (e.g., those being treated with high doses of diuretics), symptomatic hypotension may occur after initiation of treatment with losartan.

Orthostatic Hypotension Comparison

• Losartan may cause symptomatic hypotension in volume- or salt-depleted patients, which can be a risk factor for orthostatic hypotension.
• Hydrochlorothiazide (HCTZ) can potentiate orthostatic hypotension when given with certain drugs, such as alcohol, barbiturates, or narcotics. Based on the available information, HCTZ may be worse for orthostatic hypotension due to its potential to potentiate orthostatic hypotension when combined with other substances 2. However, losartan also carries a risk of symptomatic hypotension in certain patients 3.

From the Research

Orthostatic Hypotension and Medications

• Orthostatic hypotension is defined as a drop in systolic blood pressure of at least 20mmHg or a drop in diastolic blood pressure of at least 10mmHg within 3minutes of standing 4.
• The management of orthostatic hypotension can be challenging, particularly in cases where supine hypertension is associated with severe orthostatic hypotension, and education of the patient, non-pharmacological measures, and drug adaptation are the cornerstones of treatment 4.

Losartan and HCTZ

• A study evaluated the antihypertensive efficacy of the concomitant administration of selected doses of hydrochlorothiazide (HCTZ) on a background of losartan potassium (losartan) 50 mg, and found that the addition of HCTZ 12.5 mg or 25 mg to losartan 50 mg produced effective control of blood pressure in a substantial majority of patients who only partially responded to losartan monotherapy 5.
• There were no reports of orthostatic hypotension in any of the treatment groups in this study 5.
• Another study found that treatment with losartan/hydrochlorothiazide (Lo/HTCZ) enabled a substantial proportion of hypertensive patients with associated diseases to achieve the recommended goal of <140 mm Hg, and adverse effects such as orthostatic hypotension and considerable reductions in BP (>30 mmHg SBP) were rare 6.

Comparison of Losartan and HCTZ

• There is no direct comparison of losartan and HCTZ in terms of their effects on orthostatic hypotension in the provided studies.
• However, it can be noted that orthostatic hypotension is a common disorder, especially in high-risk populations such as elderly subjects and patients with neurological diseases, and is associated with markedly increased morbidity and mortality 4, 7, 8.

Treatment of Orthostatic Hypotension

• First-line therapies for orthostatic hypotension are midodrine and fludrocortisone, which may need to be combined for optimal care of severe cases 4.
• Specific pharmacological and non-pharmacological interventions have been established for the treatment of orthostatic hypotension, but randomized data evaluating the impact of therapeutic interventions on morbidity and mortality outcomes are lacking 8.