Efficacy and tolerability of irbesartan, an angiotensin II receptor antagonist, in primary hypertension - A double-blind, placebo-controlled, dose-titration study

This study compared the efficacy and tolerability of two dose-titrated regimens of irbesartan, an angiotensin II receptor antagonist selective for the AT(1) subtype, vs placebo in hypertensive patients when titrated to clinical response. Patients with seated diastolic blood pressure (SeDBP) 95 to 110mm Hg following a 4- to 5-week single-blind placebo lead-in period were randomised to double-blind irbesartan 75mg, 150mg or matching placebo administered orally once daily for 12 weeks. At week 6, the dose of double-blind medication was doubled for patients with SeDBP greater than or equal to 90mm Hg. The primary outcome measure was change from baseline in SeDBP at week 12 of double-blind treatment. Mean changes from baseline in SeDBP were significantly greater for irbesartan 75mg/150mg (-8.3mm Hg) acid 150mg/300mg. (-10.5mm Hg) dose regimens vs placebo (-4.2mm Hg) [p < 0.01]. At week 12, greater proportions of patients receiving irbesartan 75mg/150mg and 150mg/300mg achieved normalised blood pressure (SeDBP <90mm Hg) vs placebo (38, 53 and 24%, respectively; p < 0.01). Irbesartan was well tolerated, without evidence of dose-related adverse events. In the present study, irbesartan demonstrated dose-dependent reductions in blood pressure vs placebo. Both irbesartan regimens were equally well tolerated; however, blood pressure reduction was greater with the 150mg/300mg dose regimen. Initiation with irbesartan 150mg once daily and titrating to 300mg (if necessary) is an effective, well-tolerated, and efficient strategy for normalising blood pressure in patients with mild-to-moderate hypertension.