What are the best first-line agents to treat Hypertension (High Blood Pressure)?

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Last updated: February 23, 2025View editorial policy

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From the Guidelines

The best first-line agents for treating hypertension are thiazide diuretics, calcium channel blockers (CCBs), and angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), as they have been shown to be effective in reducing blood pressure and preventing cardiovascular outcomes 1.

Key Considerations

  • The choice of initial medication should be individualized based on the patient's age, race, comorbidities, and potential side effects.
  • Thiazide diuretics, such as chlorthalidone, are a good initial choice for many patients, especially for those with heart failure or chronic kidney disease.
  • CCBs, such as amlodipine, are effective in older patients and African Americans.
  • ACE inhibitors or ARBs, such as lisinopril or losartan, are often preferred in patients with diabetes or chronic kidney disease.

Mechanisms of Action

  • Thiazide diuretics reduce blood volume by increasing urine production.
  • CCBs relax blood vessels, reducing peripheral resistance.
  • ACE inhibitors and ARBs block the renin-angiotensin system, reducing blood pressure.

Dosing and Titration

  • Starting with a low dose and titrating up as needed helps minimize side effects while achieving blood pressure control.
  • For example, thiazide diuretics can be started at 12.5-25 mg daily, CCBs at 5 mg daily, and ACE inhibitors or ARBs at 10-50 mg daily.

Recent Guidelines

  • The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline recommends thiazide diuretics, CCBs, and ACE inhibitors or ARBs as first-line agents for hypertension treatment 1.
  • The 2022 WHO guideline also recommends these classes of medications as initial treatment for hypertension, with a strong recommendation and high-quality evidence 1.

From the FDA Drug Label

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits Lisinopril tablets USP may be administered alone or with other antihypertensive agents [see Clinical Studies (14.1)]. In controlled clinical studies, metoprolol has been shown to be an effective antihypertensive agent when used alone or as concomitant therapy with thiazide-type diuretics, at oral dosages of 100 to 450 mg daily

The best first-line agents to treat Hypertension (High Blood Pressure) include:

  • Lisinopril
  • Metoprolol These drugs have been shown to be effective in reducing cardiovascular morbidity and mortality, and can be used alone or in combination with other antihypertensive agents 2 3.

From the Research

First-Line Agents for Hypertension Treatment

The following are the best first-line agents to treat hypertension:

  • Angiotensin-Converting Enzyme Inhibitors (ACEi) and Angiotensin Receptor Blockers (ARBs) 4
  • Calcium Channel Blockers (CCBs) 5
  • Thiazide Diuretics 6, 7

Benefits of Each Agent

  • ACEi and ARBs: reduce mortality, stroke, coronary heart disease, and total cardiovascular events 4, 8, 6, 7
  • CCBs: reduce stroke, total cardiovascular events, and have a comparable antihypertensive efficacy to ACEi and ARBs 5, 6, 7
  • Thiazide Diuretics: reduce mortality, stroke, coronary heart disease, and total cardiovascular events, especially when used at low doses 6, 7

Comparison of Agents

  • Low-dose thiazides are more effective than high-dose thiazides and beta-blockers in reducing morbidity and mortality outcomes 6, 7
  • ACE inhibitors and calcium channel blockers may be similarly effective to low-dose thiazides, but the evidence is less robust 6, 7
  • Beta-blockers are inferior to low-dose thiazides in reducing morbidity and mortality outcomes 6, 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

First-line drugs for hypertension.

The Cochrane database of systematic reviews, 2018

Research

First-line drugs for hypertension.

The Cochrane database of systematic reviews, 2009

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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