What are the first line agents for hypertension (HTN)?

From the Guidelines

First-line antihypertensive agents should include ACE inhibitors, ARBs, thiazide-like diuretics, or dihydropyridine calcium channel blockers, with ACE inhibitors or ARBs recommended as first-line therapy for patients with diabetes and established coronary artery disease. When considering the management of hypertension, it's essential to prioritize the reduction of cardiovascular events and the protection of kidney function, particularly in patients with diabetes. According to the most recent guidelines 1, initial treatment for hypertension should include any of the drug classes demonstrated to reduce cardiovascular events in people with diabetes.

Key Considerations for First-Line Therapy

• ACE inhibitors (e.g., lisinopril) or ARBs (e.g., losartan) are preferred for patients with diabetes, chronic kidney disease, or heart failure due to their renoprotective and cardioprotective effects.
• Thiazide-like diuretics (e.g., hydrochlorothiazide or chlorthalidone) and dihydropyridine calcium channel blockers (e.g., amlodipine) are also effective options for first-line therapy.
• Beta-blockers are not recommended as first-line therapy for uncomplicated hypertension but are important for specific conditions like coronary artery disease or heart failure.
• Blood pressure goals generally target <130/80 mmHg for most adults, though this may vary based on individual risk factors and tolerability.

Individualizing Treatment

Treatment should be tailored to the individual patient, taking into account comorbidities, potential side effects, cost, and patient preferences. For example, in patients with albuminuria, ACE inhibitors or ARBs are recommended to reduce the risk of progressive kidney disease 1. In contrast, for patients without albuminuria, the choice of first-line agent may depend on other factors, such as the presence of coronary artery disease or heart failure.

Recent Guidelines and Evidence

The 2024 guidelines from the Diabetes Care journal 1 emphasize the importance of individualizing treatment and selecting agents that have been shown to reduce cardiovascular events in patients with diabetes. While earlier guidelines, such as those from 2018 1 and 1, provide additional context and support for the use of thiazide diuretics, CCBs, ACEIs, and ARBs as first-line agents, the most recent evidence should guide clinical decision-making.

From the FDA Drug Label

The usual starting dose of losartan is 50 mg once daily. Losartan was effective in reducing blood pressure regardless of race, although the effect was somewhat less in Black patients (usually a low-renin population) 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

First line hypertension agents include:

• Losartan: starting dose of 50 mg once daily
• Metoprolol: effective antihypertensive agent at oral dosages of 100 to 450 mg daily Note: The choice of first-line agent may depend on individual patient characteristics and clinical judgment 223

From the Research

First Line Hypertension Agents

• The initial pharmacologic therapy for hypertension includes low-dose thiazide diuretics, beta-blockers, and ACE inhibitors 4.
• ACE inhibitors have specific benefits in patients with diabetes, atherosclerosis, left ventricular dysfunction, and renal insufficiency 4.
• Calcium channel blockers (CCBs) are alternative agents for isolated systolic hypertension (ISH) in the elderly and appear to decrease stroke 4.
• Angiotensin II receptor blockers (ARBs) are well tolerated and effective blood pressure lowering agents, but have not been confirmed as effective as ACE inhibitors for reducing renal progression, clinical events, or mortality from heart failure 4.

Combination Therapy

• Low-dose combination therapy may be an important early alternative to up-titration of monotherapy in patients who are nonresponders to first-line monotherapy with a calcium channel blocker 5.
• The use of low-dose combination therapy in patients who are nonresponders to first-line monotherapy provides greater blood pressure control than up-titration to higher dose monotherapy 5.
• Combining two different classes of antihypertensive drugs has an additive effect on lowering blood pressure and does not increase adverse events 6.
• Triple fixed-dose combination therapy with an ARB, a CCB, and a thiazide diuretic is a rational combination for patients who require multiple antihypertensive drugs to achieve recommended blood pressure goals 6.

Recent Advances

• Recent advances include listing of four dual combinations on the WHO Essential Medicines List, completion of a triple half-dose combination trial, and a pilot of quadruple quarter-dose combination 7.
• Low-dose combination therapy is a promising option for initial treatment of hypertension that appears to be safe and effective 7.
• Larger trials of triple and quadruple low-dose combination therapy in multiple locations are underway and should provide stronger evidence of efficacy as well as information on the side effect profile 7.