Angiotensin II-Receptor Antagonists: An Overview

Raquel Dina and Mahtab Jafari


Am J Health Syst Pharm. 2000;57(13) 

In This Article

Comparative Efficacy

Other Antihypertensive Classes

Several clinical trials have demonstrated that AT-II-receptor antagonists are as effective as other antihypertensive classes (calcium-channel blockers, b-blockers, and ACE inhibitors) in lowering blood pressure.[29,31,46,50,66,78,79,80,81,82,83,84,85]

Several AT-II-receptor antagonists have been compared with several ACE inhibitors ( Table 2 ). A double- blind, multicenter, randomized study of 227 patients with mild to moderate hypertension evaluated the efficacy of candesartan cilexetil 4-8 mg once daily and enalapril maleate 10-20 mg once daily for eight weeks.[56] These two agents were equally efficacious. Mean reductions in sitting systolic and diastolic blood pressure were 10.5 and 10.1 mm Hg with candesartan and 15.0 and 12.3 mm Hg with enalapril. Adverse reactions were more frequent in the enalapril group (23.5%) than in the candesartan group (11.3%). Headache and cough were among the most common adverse events.

In another study, irbesartan and enalapril were compared for antihypertensive efficacy and tolerability in 182 patients with severe hypertension. [46] The primary endpoint was a reduction in diastolic blood pressure to normal (<90 mm Hg) or a reduction at week 12 of ≥10 mm Hg from baseline. At the end of the study period, 59% of the irbesartan recipients and 57% of the enalapril group had normal diastolic blood pressure. Response rates were similar in the irbesartan and the enalapril groups (100% and 98%, respectively). Irbesartan was associated with a lower rate of adverse events (55%) than enalapril (64%). A significantly higher percentage of patients receiving enalapril than irbesartan had cough (13.1% versus 2.5%). The results demonstrate that irbesartan is as effective as and more tolerable than enalapril, which might contribute to improved patient compliance.

A study comparing eprosartan and enalapril in patients with mild to moderate hypertension (n = 528) and patients with severe hypertension (n = 118) yielded results similar to those of comparisons between other AT-II-receptor antagonists and ACE inhibitors. [66,82] In the patients with mild to moderate hypertension, eprosartan and enalapril produced similar decreases in systolic and diastolic blood pressure reductions of 15.5 and 12.9 mm Hg, respectively, with eprosartan 600 mg/day and reductions of 14.7 and 11.9 mm Hg with enalapril maleate 20 mg/day. Among the patients with severe hypertension, systolic blood pressure was reduced by 29.1 mm Hg and diastolic blood pressure by 20.1 mm Hg in those given eprosartan and by 21.1 and 16.2 mm Hg in those given enalapril. Eprosartan was at least as effective in reducing blood pressure as enalapril and was associated with a lower frequency of dry cough (2.2% versus 20.5%).

Several trials have compared AT-II-receptor antagonists. One study involving 334 patients with mild to moderate hypertension showed that candesartan cilexetil 8 mg once daily is as effective as losartan potassium 50 mg once daily, but candesartan cilexetil 16 mg once daily had a greater blood pressure-low- ering effect than losartan potassium 50 mg once daily.[50,54] At 24 hours after a dose, there was a 3.7-mm Hg difference in sitting diastolic blood pressure and a 4.6-mm Hg difference in sitting systolic blood pressure between candesartan cilexetil 16 mg once daily and losartan potassium 50 mg once daily, in candesartan's favor. [54] In addition, the response rate was significantly higher in patients who received candesartan cilexetil 8 or 16 mg/day (50% and 57%, respectively) than in those given placebo (15%) or losartan (46%).

Another study compared the tolerability and antihypertensive efficacy of irbesartan and losartan in 567 patients with mild to moderate hypertension. [86] Irbesartan 150 or 300 mg and losartan potassium 100 mg were administered daily for eight weeks. Systolic blood pressure and diastolic blood pressure were reduced more by irbesartan 300 mg (16.4 and 11.7 mm Hg, respectively) than by losartan potassium 100 mg (11.3 and 8.7 mm Hg). At the end of the study, 52% of patients who received irbesartan 300 mg had normal blood pressure, compared with 42% of patients given losartan potassium 100 mg. Irbesartan 150 mg produced reductions in systolic and diastolic blood pressure (12.1 and 9.7 mm Hg, respectively) similar to those achieved by losartan potassium 100 mg (11.3 and 8.7 mm Hg). Both agents were well tolerated, as was found in previous trials. [18,20,40,43]

The results of these two studies suggest that candesartan and irbesartan are slightly more effective than losartan. Additional studies are needed to confirm these findings and to evaluate the effect of AT-II-receptor antagonists on hypertension-associated morbidity and mortality.

Several studies have evaluated the efficacy of AT-II-receptor antagonists in combination with hydrochlorothiazide. [58,66,71,81,82,84,87] Blood pressure response was enhanced to various degrees when hydrochlorothiazide 12.5-25 mg was administered concurrently with an AT-II-receptor antagonist, relative to the response to monotherapy with an AT-II-receptor antagonist.

It has been postulated that therapy with an AT-II-receptor antagonist in combination with an ACE inhibitor will completely block the RAS.


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