Losartan versus valsartan in the treatment of patients with mild to moderate essential hypertension: Data from a multicenter, randomized, double-blind, 12-week trial

Background: Losartan. the first of the angiotensin II receptor blockers (AR Bs) to be introduced. has been studied extensively in comparison with other classes of antihypertensive agents. Less research has been conducted on th e efficacy and tolerability of losartan tan compared with that of other ARB s. Objective: This randomized, multicenter, double-blind. parallel-group equiv alence study was conducted to compare the antihypertensive efficacy and tol erability of a once-daily regimen of losartan with that of valsartan. Methods: Patients greater than or equal to 21 years of age with mild to mod erate hypertension, defined as a trough sitting diastolic blood pressure (S iDBP) between 95 and 115 min Hg, were randomized to receive once-daily losa rtan (50 mg) or valsartan (80 mg) for 12 weeks. At the end of the sixth tre atment week, patients in both groups with trough SiDBP greater than or equa l to 90 min Hg had their dose doubled for the remainder of the treatment pe riod. Analysis of variance was used to compare treatment groups with respec t to change in mean trough SiDBP from baseline to week 12. Within-treatment changes were analyzed using the paired t test. With at least 220 patients per treatment group, the study had 90% power to place a 90% CI on the diffe rence between losartan and valsartan in SiDBP within the equivalence interv al of +/-2.5 min Hg. Results: A total of 495 patients were randomized. 247 to the losartan group and 248 to the valsartan group; 456 patients completed the study. Adjusted mean change from baseline values for trough SiDBP at the end of 12 weeks o f treatment were significantly different (P < 0.001) from zero in both the losartan group (-9.9 mm Hg) and the valsartan group (-10.1 in mm Hg). At we ek 12, losartan was as effective as valsartan in lowering SiDBP, with a bet ween-group difference of 0.2 mm Hg (90% CI, -1.3 to 1.7; P = 0.827). At wee k 6, the difference in SiDBP between groups was -1.3 mm Hg (90% CI, -2.7 to 0.0, P = 0. 106). A similar pattern of results was obtained at weeks 6 and 12 for sitting systolic blood pressure. The percentage of patients reachin g the SiDBP goal at week 6 (46% [112/241] losartan; 42% [103/245] valsartan ) and week 12 (57% [139/243] losartan: 59% [145/245] valsartan) was not sig nificantly different between the treatment groups. Both losartan and valsar tan were similarly well tolerated. Over the 12 weeks, the laboratory profil es of the 2 drugs were similar except for serum uric acid levels, which dec reased from 6.0 to 5.7 mg/dL in the losartan group and increased from 5.9 t o 6.0 mg/dL in the valsartan group (P = 0.001 for between-treatment diftere nce). Conclusions: At starting and titrated doses, losartan and valsartan are sim ilarly effective in reducing blood pressure in patients with mild to modera te hypertension. Losartan, but not valsartan, was associated with a decreas e in serum uric acid levels.