What are the first-line antihypertensive agents and their dosing for initial management of hypertension?

From the Guidelines

The first-line antihypertensive agents for initial management of hypertension include thiazide diuretics, angiotensin converting-enzyme inhibitors, angiotensin receptor blockers, and long-acting dihydropyridine calcium channel blockers, as recommended by the World Health Organization 1. For thiazide diuretics, hydrochlorothiazide is typically started at 12.5-25 mg daily, or chlorthalidone at 12.5-25 mg daily.

• Calcium channel blockers like amlodipine are initiated at 2.5-5 mg daily.
• Angiotensin-converting enzyme inhibitors (ACEIs) such as lisinopril begin at 5-10 mg daily.
• Angiotensin II receptor blockers (ARBs) like losartan start at 25-50 mg daily. Treatment should be individualized based on comorbidities; for example, ACEIs or ARBs are preferred in patients with diabetes or chronic kidney disease, while beta-blockers (such as metoprolol 25-50 mg twice daily) are beneficial for patients with coronary artery disease or heart failure. Start with a low dose and titrate upward every 2-4 weeks until blood pressure goals are achieved. Monitor for side effects including electrolyte abnormalities with diuretics, cough with ACEIs, and ankle edema with CCBs. These medications work through different mechanisms:
• diuretics reduce blood volume,
• CCBs relax vascular smooth muscle, and
• ACEIs/ARBs block the renin-angiotensin-aldosterone system that causes vasoconstriction. The American College of Cardiology/American Heart Association also supports the use of these agents as first-line therapy, with consideration of patient-specific factors and comorbidities 1. Additionally, the choice of initial monotherapy versus initial combination drug therapy should be based on the patient's blood pressure level and risk factors, with initiation of antihypertensive drug therapy with 2 first-line agents of different classes recommended in adults with stage 2 hypertension and an average BP more than 20/10 mm Hg above their BP target 1. It is also important to consider the role of lifestyle modifications, such as weight reduction, reduction of sodium intake, and increased consumption of fruits, vegetables, and low-fat dairy products, in the management of hypertension 1.

From the FDA Drug Label

DOSAGE & ADMINISTRATION 2. 1 Hypertension Initial Therapy in adults: The recommended initial dose is 10 mg once a day. The usual starting dose of losartan is 50 mg once daily. The adult initial dose of hydrochlorothiazide capsules is one capsule given once daily whether given alone or in combination with other antihypertensives.

The first-line antihypertensive agents and their dosing for initial management of hypertension are:

• Lisinopril (PO): 10 mg once daily, with a usual dosage range of 20 mg to 40 mg per day administered in a single daily dose 2
• Losartan (PO): 50 mg once daily, with a maximum dose of 100 mg once daily as needed to control blood pressure 3
• Hydrochlorothiazide (PO): one capsule given once daily, with total daily doses greater than 50 mg not recommended 4

From the Research

First-Line Antihypertensive Agents

The first-line antihypertensive agents include:

• Thiazide diuretics
• Beta-blockers
• Calcium channel blockers
• Angiotensin converting enzyme (ACE) inhibitors
• Angiotensin II receptor blockers (ARBs)
• Alpha-adrenergic blockers

Dosing for Initial Management of Hypertension

The dosing for initial management of hypertension varies depending on the agent used.

• Thiazide diuretics: low-dose thiazides are recommended as first-line treatment 5, 6
• Beta-blockers: the dose varies depending on the specific agent, but they are often used in combination with other agents 5, 6
• Calcium channel blockers: the dose varies depending on the specific agent, but they are often used in combination with other agents 5, 6
• ACE inhibitors: the dose varies depending on the specific agent, but they are often used in combination with other agents 5, 6
• ARBs: the dose varies depending on the specific agent, but they are often used in combination with other agents 7, 8, 9
• Alpha-adrenergic blockers: the dose varies depending on the specific agent, but they are often used in combination with other agents 5

Combination Therapy

Combination therapy is often required to achieve blood pressure targets.

• The combination of an ARB, a calcium channel blocker, and a thiazide diuretic is a rational combination according to the European guidelines 7
• Triple combination therapy has been shown to be effective in reducing blood pressure and achieving blood pressure targets without increasing adverse event risk 9
• The use of fixed-dose combinations can improve blood pressure control and aid compliance with long-term therapy 7, 9

Key Findings

• First-line low-dose thiazides reduce mortality, total cardiovascular events, stroke, and coronary heart disease 6
• First-line ACE inhibitors reduce mortality, stroke, coronary heart disease, and total cardiovascular events 6
• First-line calcium channel blockers reduce stroke and total cardiovascular events, but the evidence is of lower quality 6
• Combination therapy with an ARB, a calcium channel blocker, and a thiazide diuretic is effective in reducing blood pressure and achieving blood pressure targets 7, 8, 9