What is the comparison between Candesartan (Angiotensin II receptor antagonist), Losartan (Angiotensin II receptor antagonist), and Lisinopril (Angiotensin-converting enzyme inhibitor)?

From the Guidelines

Lisinopril, an ACE inhibitor, is generally recommended as the first-line treatment for patients with hypertension, due to its once-daily dosing, lower cost, and extensive clinical experience, unless the patient develops a dry cough, in which case an ARB like losartan or candesartan is preferred 1.

Comparison of Medications

The main difference between lisinopril, losartan, and candesartan is their mechanism of action. Lisinopril is an ACE inhibitor, while losartan and candesartan are angiotensin II receptor blockers (ARBs).

• ACE inhibitors, like lisinopril, have been shown to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF) 1.
• ARBs, like losartan and candesartan, are recommended for patients who are intolerant to ACE inhibitors due to cough or angioedema, and have been shown to reduce mortality and HF hospitalizations in patients with HFrEF 1.

Dosage and Administration

• Lisinopril is typically started at a dose of 10mg daily and can be titrated up to 40mg daily 1.
• Losartan is typically started at a dose of 50mg daily and can be titrated up to 100mg daily 1.
• Candesartan is typically started at a dose of 8mg daily and can be titrated up to 32mg daily 1.

Side Effects and Contraindications

• All three medications are contraindicated in pregnancy and require monitoring of kidney function and potassium levels 1.
• ACE inhibitors, like lisinopril, can cause a dry cough in up to 20% of patients, while ARBs, like losartan and candesartan, have a lower incidence of cough and angioedema 1.

Patient-Specific Considerations

• The choice between these medications should be individualized based on cost considerations, side effect profile, comorbidities (particularly beneficial in heart failure, diabetes with kidney disease), and patient preference regarding dosing schedule 1.
• Losartan has the additional benefit of increasing uric acid excretion, making it useful for patients with gout 1.
• Candesartan is generally more potent and has longer-lasting effects than losartan, but is typically more expensive 1.

From the FDA Drug Label

CLINICAL PHARMACOLOGY Mechanism of Action Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin II is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium Candesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin II from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because candesartan does not inhibit ACE (kininase II), it does not affect the response to bradykinin Whether this difference has clinical relevance is not yet known.

The comparison between Candesartan (Angiotensin II receptor antagonist), Losartan (Angiotensin II receptor antagonist), and Lisinopril (Angiotensin-converting enzyme inhibitor) is as follows:

• Mechanism of Action:
  • Candesartan and Losartan block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor.
  • Lisinopril inhibits the biosynthesis of angiotensin II from angiotensin I.
• Key Differences:
  • Candesartan and Losartan do not affect the response to bradykinin, whereas Lisinopril inhibits the degradation of bradykinin.
  • The clinical relevance of this difference is not yet known. There is no direct comparison of the efficacy of Candesartan, Losartan, and Lisinopril in the provided drug labels 2 3.

From the Research

Comparison of Candesartan, Losartan, and Lisinopril

• Candesartan and Losartan are Angiotensin II receptor antagonists, while Lisinopril is an Angiotensin-converting enzyme inhibitor 4, 5.
• Both Angiotensin II receptor antagonists and Angiotensin-converting enzyme inhibitors have been shown to be effective in treating hypertension and heart failure, but they differ in their mechanism of action and adverse effects 4, 5.
• Candesartan and Losartan have been compared to ACE inhibitors such as Captopril in clinical trials, with no significant difference found in terms of mortality or clinical deterioration in patients with heart failure 4.
• Lisinopril has been shown to be an effective antihypertensive agent, with a comparable efficacy to other ACE inhibitors such as Captopril 5, 6.
• Angiotensin II receptor antagonists such as Candesartan and Losartan may have a lower incidence of certain adverse effects such as cough and skin rash compared to ACE inhibitors like Lisinopril 4, 7.
• However, both classes of drugs can cause serious adverse effects such as hyperkalemia, renal failure, and hypotension 4, 5.

Clinical Use

• Candesartan and Losartan are used to treat hypertension and heart failure, while Lisinopril is used to treat hypertension, heart failure, and diabetic nephropathy 4, 5, 7.
• The choice of initial antihypertensive drug therapy should be based on sound scientific data and the patient's perspective and needs, with consideration of factors such as efficacy, side effects, and dosing frequency 8.
• Low-dose thiazide diuretics, Angiotensin II receptor antagonists, and Angiotensin-converting enzyme inhibitors are all potential options for initial antihypertensive therapy, depending on the patient's individual characteristics and needs 8.

Adverse Effects

• Common adverse effects of Candesartan and Losartan include dizziness, cough, and rash, while Lisinopril can cause cough, azotemia, angioedema, hypotension, and hyperkalemia 4, 5, 6.
• Both Angiotensin II receptor antagonists and Angiotensin-converting enzyme inhibitors can cause serious adverse effects such as renal failure and hyperkalemia, especially in patients with pre-existing renal disease or those taking other medications that affect renal function 4, 5.