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 selecti ve for the AT(1) subtype, vs placebo in hypertensive patients when tit rated to clinical response. Patients with seated diastolic blood press ure (SeDBP) 95 to 110mm Hg following a 4- to 5-week single-blind place bo lead-in period were randomised to double-blind irbesartan 75mg, 150 mg 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 measu re was change from baseline in SeDBP at week 12 of double-blind treatm ent. Mean changes from baseline in SeDBP were significantly greater fo r irbesartan 75mg/150mg (-8.3mm Hg) acid 150mg/300mg. (-10.5mm Hg) dos e regimens vs placebo (-4.2mm Hg) [p < 0.01]. At week 12, greater prop ortions of patients receiving irbesartan 75mg/150mg and 150mg/300mg ac hieved normalised blood pressure (SeDBP <90mm Hg) vs placebo (38, 53 a nd 24%, respectively; p < 0.01). Irbesartan was well tolerated, withou t evidence of dose-related adverse events. In the present study, irbes artan demonstrated dose-dependent reductions in blood pressure vs plac ebo. Both irbesartan regimens were equally well tolerated; however, bl ood 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 fo r normalising blood pressure in patients with mild-to-moderate hyperte nsion.