Candesartan cilexetil is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Angiotensin II receptor antagonists, such as candesartan cilexetil, are considered one of several preferred antihypertensive drugs for the initial management of hypertension; other options include angiotensin-converting enzyme (ACE) inhibitors, calcium-channel blockers, and thiazide diuretics. While there may be individual differences with respect to specific outcomes, these antihypertensive drug classes all produce comparable effects on overall mortality and cardiovascular, cerebrovascular, and renal outcomes.Angiotensin II receptor antagonists or ACE inhibitors may be particularly useful in the management of hypertension in patients with certain coexisting conditions such as diabetes mellitus or chronic kidney disease; angiotensin II receptor antagonists also may be preferred, generally as an alternative to ACE inhibitors, in hypertensive patients with heart failure or ischemic heart disease and/or postmyocardial infarction.
Efficacy of candesartan cilexetil in the treatment of hypertension was established in placebo-controlled studies of 4-12 weeks' duration in patients with hypertension of mild to moderate severity. In these patients, candesartan cilexetil dosages of 8-32 mg daily decreased systolic blood pressure by about 8-12 mm Hg and diastolic blood pressure by about 4-8 mm Hg 24 hours after dosing. After withdrawal of candesartan cilexetil, blood pressure gradually returns to pretreatment levels; rebound hypertension following abrupt withdrawal of the drug has not been reported.
The efficacy of candesartan cilexetil for long-term use (i.e., exceeding 12 weeks) has been established in 2 open label, prospective studies in which the drug was administered in dosages 4-16 mg once daily for 6 or 12 months without apparent loss of clinical effect. Clinical studies have shown that the hypotensive effect of candesartan cilexetil in patients with mild to moderate hypertension is greater than that of placebo and comparable to that of usual dosages of enalapril or amlodipine. Like ACE inhibitors, angiotensin II receptor antagonists such as candesartan may produce a smaller blood pressure response in hypertensive black patients compared with nonblack patients.
For additional information on the management of hypertension, For information on overall principles and expert recommendations for treatment of hypertension,
Candesartan is used in the management of mild to severe (New York Heart Association [NYHA] class II-IV) heart failure secondary to left ventricular dysfunction (i.e., a left ventricular ejection fraction [LVEF] of 40% or less) to reduce cardiovascular death and heart failure-associated hospitalization.
Current guidelines for the management of heart failure in adults generally recommend a combination of drug therapies to reduce morbidity and mortality, including neurohormonal antagonists (e.g., ACE inhibitors, angiotensin II receptor antagonists, angiotensin receptor-neprilysin inhibitors [ARNIs], β-adrenergic blocking agents (β-blockers), aldosterone receptor antagonists) that inhibit the detrimental compensatory mechanisms in heart failure. Additional agents (e.g., cardiac glycosides, diuretics, sinoatrial modulators [i.e., ivabradine]) added to a heart failure treatment regimen in selected patients have been associated with symptomatic improvement and/or reduction in heart-failure related hospitalizations. Experts recommend that all asymptomatic patients with reduced LVEF (American College of Cardiology Foundation [ACCF]/American Heart Association [AHA] stage B heart failure) receive therapy with an ACE inhibitor and β-blocker to prevent symptomatic heart failure and to reduce morbidity and mortality. In patients with prior or current symptoms of chronic heart failure with reduced LVEF (ACCF/AHA stage C heart failure), ACCF, AHA, and the Heart Failure Society of America (HFSA) recommend inhibition of the renin-angiotensin-aldosterone (RAA) system with an ACE inhibitor, angiotensin II receptor antagonist, or ARNI in conjunction with a β-blocker, and an aldosterone antagonist in selected patients, to reduce morbidity and mortality. While ACE inhibitors have been the preferred drugs for inhibition of the RAA system because of their established benefits in patients with heart failure and reduced ejection fraction, some evidence indicates that therapy with sacubitril/valsartan, an ARNI, may be more effective than ACE inhibitor therapy (enalapril) in reducing cardiovascular death and heart failure-related hospitalization. ACCF, AHA, and HFSA recommend that patients with chronic symptomatic heart failure with reduced LVEF (NYHA class II or III) who are able to tolerate an ACE inhibitor or angiotensin II receptor antagonist be switched to therapy containing an ARNI to further reduce morbidity and mortality. However, in patients in whom an ARNI is not appropriate, continued use of an ACE inhibitor for all classes of heart failure with reduced ejection fraction remains strongly advised. In patients in whom an ARNI or ACE inhibitor is not appropriate, an angiotensin II receptor antagonist may be used. For further information on the use of ARNIs in patients with heart failure, see Uses: Heart Failure, in Sacubitril and Valsartan 24:32.92.
The manufacturer states that beneficial effects of candesartan have been shown to be additive with those of ACE inhibitors. However, patients receiving such combination therapy should be closely monitored. (See Drug Interactions: Drugs that Block the Renin-Angiotensin System.)
While angiotensin II receptor antagonists are considered reasonable alternatives in patients who are unable to tolerate ACE inhibitors (e.g., because of cough or angioedema), sensitivity reactions (e.g., various anaphylactoid reactions and/or angioedema) have been reported with use of angiotensin II receptor antagonists, including candesartan. (See Warnings: Sensitivity Reactions, under Warnings/Precautions in Cautions.)
Efficacy of candesartan for the management of heart failure has been studied in a large (2028 patients), multicenter, double-blind, placebo-controlled, randomized study (Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity [CHARM]-Alternative) in patients (32% were female and the mean age of all patients was 67 years) with NYHA class II-IV heart failure and a mean LVEF of 30%, who were intolerant of ACE inhibitors. Addition of candesartan cilexetil 4-8 mg once daily (initial dosage, with dosage doubled every 2 weeks to a target dosage of 32 mg once daily [mean daily dosage about 23 mg]) to standard therapy (diuretics, digoxin, β-blockers, spironolactone) was associated with a 23% reduction (compared with placebo) in the primary end point of cardiovascular death or hospitalization for worsened heart failure at a median follow-up of 34 months.
Efficacy of candesartan for the management of heart failure has been studied in a second large (2548 patients), multicenter, double-blind, placebo-controlled, randomized study (CHARM-Added) in patients (21% were female and the mean age of all patients was 64 years) with NYHA class II-IV heart failure and a mean LVEF of 28%. Addition of candesartan cilexetil 4-8 mg once daily (initial dosage, with dosage doubled every 2 weeks to a target dosage of 32 mg once daily [mean daily dosage about 24 mg]) to standard therapy (ACE inhibitors, diuretics, digoxin, β-blockers, spironolactone) was associated with a 15% reduction (compared with placebo) in the primary end point of cardiovascular death or hospitalization for worsened heart failure at a median follow-up of 41 months.
A third large (3023 patients), multicenter, double-blind, placebo-controlled, randomized study (CHARM-Preserved) was conducted in patients (40% were female and the mean age of all patients was 67 years) with NYHA class II-IV heart failure and preserved LVEF (higher than 40%). Addition of candesartan cilexetil 4-8 mg once daily (initial dosage, with dosage doubled every 2 weeks to a target dosage of 32 mg once daily [mean daily dosage about 25 mg]) to standard therapy, including an ACE inhibitor in about 19% of patients, was associated with a moderate reduction in the number of patients hospitalized one or more times for heart failure but no difference in the number of cardiovascular deaths at a median follow-up of 36.6 months.
Both angiotensin II receptor antagonists and ACE inhibitors have been shown to slow the rate of progression of renal disease in patients with diabetes mellitus and persistent albuminuria, and use of a drug from either class is recommended in such patients with modestly elevated (30-300 mg/24 hours) or higher (exceeding 300 mg/24 hours) levels of urinary albumin excretion. The usual precautions of angiotensin II receptor antagonist or ACE inhibitor therapy in patients with substantial renal impairment should be observed.
(See Renal Effects under Warnings/Precautions: General Precautions, in Cautions). For additional information on the use of angiotensin II receptor antagonists in the treatment of diabetic nephropathy, and in .