COMPARATIVE EFFICACY OF 2 ANGIOTENSIN-II RECEPTOR ANTAGONISTS, IRBESARTAN AND LOSARTAN, IN MILD-TO-MODERATE HYPERTENSION

The primary objectives of this double-blind study were to compare the antihypertensive efficacy and tolerability of irbesartan and losartan, two angiotensin II (AT(1) subtype) receptor antagonists with differen t pharmacokinetic profiles in patients with mild-to-moderate hypertens ion. Both drugs are approved for once-daily use (although losartan may also be prescribed twice-daily). After a placebo lead-in, 567 patient s were randomized (1:1: 1:1) to once-daily therapy with placebo, 100 m g losartan, 150 mg irbesartan, or 300 mg irbesartan for 8 weeks. Treat ment groups had comparable demographic and baseline characteristics. A fter 8 weeks of treatment, reductions from baseline in trough seated d iastolic blood pressure (SeDBP) and trough seated systolic blood press ure (SeSBP) with 300 mg irbesartan were greater than with 100 mg losar tan (P <.01 for both comparisons), by 3.0 and 5.1 mm Hg, respectively; larger reductions were also demonstrated at weeks 1 and 4 (P <.01 and P =.017, respectively, for SeDBP). Throughout the study, the antihype rtensive effect of 150 mg irbesartan did not differ significantly from that of 100 mg losartan. All therapies were well tolerated. The 300 m g dose of irbesartan was associated with the lowest incidence of adver se events (AE) and discontinuations because of AE. This study demonstr ates that the maximally effective once-daily doses of two different AT (1) receptor antagonists may result in clinically significant differen ces in blood pressure reductions, and therefore highlights the potenti al importance of the pharmacokinetic and pharmacodynamic differences b etween these two members of this class. (C) 1998 American Journal of H ypertension, Ltd.