Is amlodipine (calcium channel blocker) or Hydrochlorothiazide (HCTZ) (thiazide diuretic) better for adjunct therapy in Hypertension (HTN)?

From the Guidelines

Amlodipine is generally preferred over Hydrochlorothiazide (HCTZ) as an adjunct therapy for hypertension due to its once-daily dosing, consistent 24-hour blood pressure control, and metabolic neutrality, as supported by the 2017 ACC/AHA guideline 1. When considering adjunct therapy for hypertension, the choice between amlodipine and HCTZ depends on individual patient factors.

• Amlodipine (5-10 mg daily) is a good option for most patients requiring a second agent, as it provides consistent 24-hour blood pressure control and has a favorable side effect profile, with its main side effect being peripheral edema 1.
• HCTZ (12.5-25 mg daily) is particularly beneficial in patients with volume overload, African American patients, and the elderly, as it increases sodium and water excretion, reducing blood volume and vascular resistance 1. However, HCTZ can cause electrolyte abnormalities, hyperuricemia, and worsen glucose tolerance and lipid profiles, which should be taken into consideration when making treatment decisions 1. Patient comorbidities should guide the selection of adjunct therapy, with HCTZ potentially being preferred in heart failure or osteoporosis, and amlodipine being better for patients with diabetes, gout, or dyslipidemia 1. The most effective approach often involves combining medications with complementary mechanisms, such as an ACE inhibitor or ARB with either amlodipine or HCTZ, to achieve optimal blood pressure control and reduce the risk of cardiovascular events 1.

From the Research

Comparison of Amlodipine and HCTZ for Adjunct Therapy in HTN

• Amlodipine and HCTZ are both effective antihypertensive agents, but their efficacy as adjunct therapy in HTN may vary.
• A study published in 1988 2 compared the long-term efficacy of amlodipine and HCTZ in patients with essential hypertension, and found that both treatments reduced blood pressure significantly, with responder rates of 74.1% for amlodipine and 69.8% for HCTZ.
• Another study published in 1993 3 also compared the long-term efficacy of amlodipine and HCTZ, and found that both treatments had comparable antihypertensive effects, with mean reductions in supine and standing systolic and diastolic blood pressure values.

Efficacy of Amlodipine as Adjunct Therapy

• A study published in 2023 4 found that amlodipine 5/10 mg/day therapy used as monotherapy or adjuvant therapy provided significant reductions in both office BP and ambulatory BP over eight weeks.
• Amlodipine has been shown to be effective in reducing blood pressure in patients with mild-to-moderate essential hypertension, with a dose-dependent effect 5.

Combination Therapy with Amlodipine and HCTZ

• A study published in 2009 6 found that a fixed-dose combination of amlodipine, valsartan, and HCTZ produced significantly greater reductions in blood pressure than dual combination therapies, and was generally well tolerated.
• The combination of amlodipine and HCTZ may be effective in patients whose blood pressure is inadequately controlled with monotherapy or dual combination therapy.

Safety and Tolerability

• Amlodipine and HCTZ have been shown to be generally well tolerated, with most adverse events being transient and of mild to moderate severity 2, 3, 6.
• However, the incidence of adverse effects was higher with amlodipine than with HCTZ in some studies 2, 3.