What is an example of an Angiotensin Receptor Blocker (ARB)?

Examples of Angiotensin Receptor Blockers (ARBs)

Common ARBs available for clinical use include losartan, valsartan, candesartan, irbesartan, telmisartan, and eprosartan. 1

First-Line ARBs by Clinical Indication

For Heart Failure with Reduced Ejection Fraction

• Candesartan (4-8 mg initially, target 32 mg once daily) and valsartan (20-40 mg twice daily initially, target 160 mg twice daily) are the preferred ARBs when ACE inhibitors cannot be tolerated, as they have proven mortality and hospitalization benefits. 1, 2
• Candesartan specifically improved outcomes in the CHARM Alternative trial for patients intolerant of ACE inhibitors. 1, 3
• Losartan should be avoided in heart failure due to weaker evidence and a trend toward harm in the OPTIMAAL trial. 2

For Hypertension with Stroke Prevention

• Losartan (25-50 mg initially, target 50-100 mg once daily) demonstrated a 13% reduction in cardiovascular events versus atenolol, primarily through 40% stroke reduction. 1, 2
• However, this benefit does not apply to Black patients—in the LIFE study, Black patients on atenolol had better outcomes than those on losartan. 2

For Hypertension (General)

The following ARBs are FDA-approved and commonly used: 1, 4, 5

• Losartan: 25-50 mg once daily initially, maximum 50-100 mg once daily
• Valsartan: 20-40 mg twice daily initially, maximum 160 mg twice daily
• Candesartan: 4-8 mg once daily initially, maximum 32 mg once daily
• Irbesartan: 150-300 mg once daily
• Telmisartan: 40-80 mg once daily
• Eprosartan: 400-800 mg once daily

Key Pharmacologic Differences

Receptor Binding Characteristics

• Candesartan exhibits insurmountable (tight-binding) antagonism at the AT1 receptor with slow dissociation, suggesting longer duration of action than predicted by its elimination half-life alone. 6
• Losartan exhibits competitive antagonism and is partially converted to a more active metabolite (EXP 3174). 7, 6
• Valsartan and irbesartan exhibit intermediate antagonism between competitive and insurmountable. 6

Bioavailability and Dosing Potency

• Bioavailability ranges from 13% (eprosartan) to 60-80% (irbesartan). 7
• On a mg-per-mg basis, antihypertensive potency follows: candesartan > telmisartan ≈ losartan > irbesartan ≈ valsartan > eprosartan. 7

Critical Safety Monitoring for All ARBs

Recheck blood pressure (including orthostatic), serum creatinine, and potassium within 1-2 weeks of ARB initiation and after each dose increase. 1, 2, 3

High-Risk Patients Requiring Closer Surveillance

• Systolic blood pressure <80 mm Hg 1
• Low serum sodium 1
• Diabetes mellitus 1
• Pre-existing renal impairment 1

Absolute Contraindications

• Pregnancy: ARBs cause fetal harm and death—discontinue immediately if pregnancy occurs. 4
• History of angioedema (though less common than with ACE inhibitors, cross-reactivity can occur). 1
• Concurrent use with aliskiren in diabetic patients. 4

Common Pitfalls to Avoid

Do Not Routinely Combine ARB + ACE Inhibitor + Aldosterone Antagonist

• Triple combination increases risk of hyperkalemia and renal dysfunction without proven mortality benefit. 1, 2
• The VALIANT trial showed that combining ARB with ACE inhibitor increased adverse events without mortality benefit. 2

Do Not Use Losartan as First-Line in Heart Failure

• Candesartan and valsartan have superior evidence for heart failure outcomes. 2, 3

Do Not Expect Benefit from Losartan in Black Patients with Left Ventricular Hypertrophy

• The LIFE study demonstrated worse outcomes with losartan compared to atenolol specifically in Black patients. 2

Monitor for Hypotension, Especially When Initiating Therapy

• ARBs can cause significant hypotension, particularly in volume-depleted patients or those on concurrent diuretics. 1, 4

Tolerability Profile

ARBs have a side effect profile comparable to placebo in most hypertension studies, with significantly fewer adverse effects than ACE inhibitors (particularly cough, which occurs in 5-10% with ACE inhibitors but is rare with ARBs). 1, 2