Irbesartan is used alone or in combination with other classes of antihypertensive agents in the management of hypertension. Angiotensin II receptor antagonists, such as irbesartan, 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 irbesartan for the management of hypertension has been established by controlled studies of 8-12 weeks' duration in patients with hypertension of mild to moderate severity in outpatient settings. Clinical studies have shown that the hypotensive effect of usual dosages of irbesartan in patients with mild to moderate hypertension is greater than that of placebo and comparable to that of usual dosages of losartan, enalapril, or atenolol.
Like ACE inhibitors, angiotensin II receptor antagonists such as irbesartan 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,
Irbesartan is used in the management of diabetic nephropathy manifested by elevated serum creatinine and proteinuria (urinary protein excretion exceeding 300 mg daily) in patients with type 2 diabetes mellitus and 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. Some evidence suggests that these drugs may slow the progression of nephropathy by a mechanism independent of their antihypertensive effects.
Comparative trials evaluating the efficacy of angiotensin II receptor antagonists and ACE inhibitors for improving renal outcomes in diabetic patients are lacking. Evidence supporting use of ACE inhibitors generally is based on studies in patients with type 1 diabetes mellitus, while evidence supporting use of angiotensin II receptor antagonists generally is based on studies in patients with type 2 diabetes mellitus. Findings from these studies indicate that both drug classes delay progression of increased urinary albumin excretion in patients with diabetes mellitus and may also slow the decline in renal function. Because the available data are consistent, some experts suggest that the effects of both drug classes in improving renal outcomes in patients with diabetes mellitus and proteinuria are likely to be similar.
Drugs that inhibit the renin-angiotensin system (i.e., angiotensin II receptor antagonists, ACE inhibitors) also have been shown to delay the onset of albuminuria in patients with type 2 diabetes mellitus and hypertension who have normal levels of urinary albumin excretion.
Although combined therapy with ACE inhibitors and angiotensin II receptor antagonists appears to have additive effects in reducing albuminuria, such combinations provide no additional cardiovascular benefit and increase the risk of adverse effects (e.g., impaired renal function, hyperkalemia). The usual precautions of angiotensin II receptor antagonist therapy in patients with substantial renal impairment should be observed.
The current labeled indication for irbesartan in hypertensive patients with type 2 diabetes mellitus and nephropathy (indicated by an elevated serum creatinine and proteinuria exceeding 300 mg/day) is based principally on the results of a long-term (mean duration of follow-up: 2.6 years), multicenter, comparative controlled trial, the Irbesartan Diabetic Nephropathy Trial (IDNT). In the IDNT, therapy with irbesartan (dosage titrated from 75 to 300 mg daily) reduced the risk of the primary composite end point, which was defined as a doubling of the baseline serum creatinine concentration, end-stage renal disease (i.e., initiation of dialysis, renal transplantation, or a serum creatinine concentration of at least 6 mg/dL), or death, by 23% compared with amlodipine therapy (dosage titrated from 2.5 to 10 mg daily) and by 20% compared with placebo. Additional antihypertensive agents (diuretics, β-adrenergic blocking agents [β-blockers], peripheral α-adrenergic blocking agents, or central α2-adrenergic agonists) were used as needed in all treatment groups to achieve a trough blood pressure of 135/85 mm Hg or less in the sitting position or 10 mm Hg reduction in systolic blood pressure if higher than 160 mm Hg; ACE inhibitors, other angiotensin II receptor antagonists, and calcium-channel blocking agents could not be used. Most of the delay in time to occurrence of composite clinical events seen with irbesartan-containing therapy was the result of a reduction in the risk of doubling of serum creatinine concentration; irbesartan-containing therapy had no appreciable effect on overall mortality, onset of end-stage renal disease, or secondary composite cardiovascular end point (death from cardiovascular causes, nonfatal myocardial infarction, hospitalization for heart failure, stroke with permanent neurologic deficit, amputation) compared with other treatments. Mean blood pressure achieved with either irbesartan- or amlodipine-containing therapies was similar (142/77 or 142/76 mm Hg, respectively) and lower than that achieved with placebo plus other antihypertensive agents (145/79 mm Hg). Despite therapy with an average of 3 other nonstudy antihypertensive agents per patient in all treatment groups, none of the treatment groups achieved the target blood pressure goal.
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-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] functional 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 .
Several clinical trials in patients with heart failure have evaluated the use of angiotensin II receptor antagonists as add-on therapy to conventional regimens compared with an ACE inhibitor, as add-on therapy to conventional regimens including an ACE inhibitor, as combination therapy with an ACE inhibitor compared with therapy with either type of agent alone, or as an alternative therapy in patients intolerant of ACE inhibitors. Data from these and other long-term placebo-controlled clinical trials indicate that angiotensin II receptor antagonists produce hemodynamic and neurohormonal effects associated with their suppression of the renin-angiotensin system; reduced hospitalizations and mortality also have been demonstrated. However, in some studies, these drugs did not show consistent effects on cardiac symptoms or exercise tolerance.
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), urticaria and angioedema (e.g., swelling of the face, lips, pharynx, and/or tongue) have been reported rarely during postmarketing experience in patients receiving irbesartan.
(See Sensitivity Reactions under Cautions: Warnings/Precautions.)