What are the two best initial antihypertensive (high blood pressure) medications, excluding diuretics, for a person with hypertension?

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From the Guidelines

The two best antihypertensive medications to start a person with high blood pressure on, excluding diuretics, are ACE inhibitors and calcium channel blockers. These medications are recommended as first-line options due to their proven efficacy in lowering blood pressure and reducing cardiovascular events, as stated in 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.

Mechanism of Action and Benefits

ACE inhibitors work by blocking the conversion of angiotensin I to angiotensin II, thereby reducing vasoconstriction and sodium retention. They are particularly beneficial for patients with diabetes, chronic kidney disease, or heart failure. Calcium channel blockers prevent calcium from entering the cells of the heart and blood vessel walls, resulting in relaxation of blood vessels and reduced blood pressure. They are especially effective in older patients and those of African descent. Both medication classes have favorable side effect profiles, though ACE inhibitors may cause a dry cough in some patients, while calcium channel blockers might lead to peripheral edema, as noted in the guideline 1.

Dosage and Administration

The dosage of ACE inhibitors can range from 10-40 mg daily for lisinopril or 2.5-20 mg daily for ramipril. Calcium channel blockers can be administered at a dose of 5-10 mg daily for amlodipine or 120-540 mg daily for diltiazem extended-release. Patients should take these medications consistently at the same time each day, and blood pressure should be monitored regularly to assess effectiveness and adjust dosing as needed, as recommended in the guideline 1.

Patient-Specific Factors

When selecting an antihypertensive medication, patient-specific factors such as age, concurrent medications, drug adherence, drug interactions, and comorbidities should be considered. For example, ACE inhibitors may be preferred in patients with diabetes or chronic kidney disease, while calcium channel blockers may be preferred in older patients or those of African descent. The guideline emphasizes the importance of shared decision making, with the patient influenced by clinician judgment, to drive the ultimate choice of antihypertensive agent(s) 1.

Combination Therapy

Many patients started on a single agent will subsequently require two drugs from different pharmacological classes to reach their blood pressure goals. Combination therapy with ACE inhibitors and calcium channel blockers can result in additive lowering of blood pressure and may improve adherence. Several two- and three-fixed-dose drug combinations of antihypertensive drug therapy are available, with complementary mechanisms of action among the components, as noted in the guideline 1.

From the FDA Drug Label

Losartan was effective in reducing blood pressure regardless of race, although the effect was somewhat less in Black patients Treatment with losartan resulted in a 13% reduction (p=0. 021) in risk of the primary endpoint compared to the atenolol group Lisinopril tablets USP are indicated for the treatment of hypertension in adult patients and pediatric patients 6 years of age and older to lower blood pressure. 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

The two best antihypertensive medications to start a person with high blood pressure on, excluding diuretics, are:

  • Losartan: an angiotensin II receptor antagonist, which has been shown to be effective in reducing blood pressure regardless of race, although the effect was somewhat less in Black patients 2.
  • Lisinopril: an angiotensin-converting enzyme (ACE) inhibitor, which is indicated for the treatment of hypertension in adult patients and pediatric patients 6 years of age and older to lower blood pressure 3.

From the Research

Antihypertensive Medications

The two best antihypertensive medications to start a person with high blood pressure on, excluding diuretics, are:

  • Angiotensin-Converting Enzyme (ACE) inhibitors, as recommended by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure 4
  • Beta blockers, also recommended by the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure 4

Alternative Options

Other options that can be considered are:

  • Angiotensin II receptor antagonists, which have been shown to be effective and well-tolerated antihypertensive agents 5, 6
  • Calcium antagonists, which are particularly indicated for managing patients with angina pectoris, paroxysmal supraventricular tachycardia, and atrial fibrillation with rapid ventricular rate 5

Combination Therapy

Combination therapy with a calcium channel blocker and an angiotensin II type 1 receptor blocker has been shown to be effective in managing hypertension, with better efficacy and tolerability compared to individual agents 7 Very-low-dose combination therapy, such as combining an ACE inhibitor or an AT1 receptor blocker with a low dose of a diuretic, can also be effective in decreasing blood pressure while maintaining tolerability 8

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Angiotensin-Converting Enzyme Inhibitors in Hypertension: To Use or Not to Use?

Journal of the American College of Cardiology, 2018

Research

Combined therapy with a calcium channel blocker and an angiotensin II type 1 receptor blocker.

Journal of clinical hypertension (Greenwich, Conn.), 2008

Research

Very-low-dose combination: a first-line choice for the treatment of hypertension?

Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 2003

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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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