Azilsartan medoxomil is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Angiotensin II receptor antagonists such as azilsartan 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 azilsartan in the treatment of hypertension has been established in 7 double-blind, randomized studies, including 5 placebo-controlled studies of 6 weeks to 6 months in duration in patients with mild, moderate, or severe hypertension. In these patients, azilsartan medoxomil dosages of 40-80 mg daily decreased placebo-corrected systolic blood pressure by about 12-15 mm Hg and diastolic blood pressure by about 6-9 mm Hg at 6 weeks. Rebound hypertension following abrupt withdrawal of the drug was not reported. Clinical studies have shown that the hypotensive effect of azilsartan is greater than that of placebo and comparable to or greater than that of olmesartan and valsartan. At maximum recommended dosages, the effect of azilsartan on clinic and 24-hour mean blood pressure measurements at 6 weeks was greater than that of olmesartan and valsartan.
Azilsartan has approximately its usual effects on blood pressure reduction when added to amlodipine or chlorthalidone treatment.
Like ACE inhibitors, angiotensin II receptor antagonists such as azilsartan may produce a smaller blood pressure response in hypertensive black patients compared with patients of other races. According to the manufacturer, the effect of monotherapy with azilsartan on blood pressure was reduced by about 50% in black patients compared with patients of other races.
For additional information on the management of hypertension, For information on overall principles and expert recommendations for treatment of hypertension,
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: Other Warnings and Precautions, in Cautions.)For additional information on the use of angiotensin II receptor antagonists in the treatment of diabetic nephropathy, and in .
Angiotensin II receptor antagonists have been used in the management of heart failure.
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 left ventricular ejection fraction (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 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 and reduced LVEF (New York Heart Association [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 additional information on the use of angiotensin II receptor antagonists in the management of heart failure, and in .
Angiotensin II receptor antagonists are considered reasonable alternative therapy in patients who are unable to tolerate ACE inhibitors (e.g., because of cough or angioedema).
(See Sensitivity Reactions under Cautions: Warnings/Precautions.)No additional therapeutic benefit has been demonstrated with concomitant use of an angiotensin II receptor antagonist and an ACE inhibitor.