Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension

Objective: The goal of this multicenter, double-blind, randomized, parallel -group study was to compare the effects of losartan potassium (hereafter re ferred to as losartan), candesartan cilexitil (hereafter referred to as can desartan), and losartan/hydrochlorothiazide (HCTZ) in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] 95-115 mm Hg). Methods: A total of 1161 patients were randomized in a 2:2:1 ratio to 12 we eks of treatment with losartan 50 mg QD, possibly titrated to 100 mg QD (n = 461); candesartan 8 mg QD, possibly titrated to 16 mg QD (n = 468); or lo sartan 50 mg QD, possibly titrated to losartan 50 mg plus HCTZ 12.5 mg QD ( n = 232). At 6 weeks, the regimens of patients not reaching a goal SiDBP <9 0 mm Hg were titrated as described, whereas patients achieving this goal co ntinued with low-dose monotherapy. The single primary end point at 12 weeks tested the equivalence of the 2 monotherapy regimens, predefined as a maxi mum betweentreatment difference in the mean change from baseline trough SiD BP of 2.5 mm Hg. Results: At 12 weeks, changes in SiDBP/sitting systolic blood pressure (SiS BP) of -12.4/-14.4 mm Hg with losartan 50 mg/100 mg and -13.1/-15.8 mm Hg w ith candesartan 8 mg/16 mg demonstrated equivalence between the 2 monothera py regimens (95% CI for difference in SiDBP, -1.6 to 0.2). At 12 weeks, the losartan 50 mg/50 mg plus HCTZ 12.5 mg regimen had reduced SiDBP/SiSBP sig nificantly more (-14.3/-18.0 mm Hg) than either the candesartan 8 mg/16 mg (SiDBP, P = 0.045; SiSBP, P = 0.017) or losartan 50 mg/100 mg regimen (SiDB P and SiSBP, P = 0.001). During the last 6 weeks, patients whose regimen ha d been titrated to losartan 50 mg plus HCTZ 12.5 mg (n = 114) showed a,orea ter reduction in SiDBP/SiSBP (-14.5/-18.7 mm Hg) than did those whose regim en had been titrated to either losartan 100 mg (-10.5/-12.3 mm Hg; n = 211) or candesartan 16 mg (-11.5/-13.2 mm Hg; n = 206), representing a clinical ly meaningful (<greater than or equal to>2.5-mm Hg) difference. All 3 treat ments were well tolerated, with few patients experiencing drug-related adve rse events (6.9% losartan 50 mg/100 mg, 7.5% candesartan 8 mg/16 mg, 3.0% l osartan 50 mg/50 mg plus HCTZ 12.5 mg). Candesartan 8 mg/16 mg increased se rum uric acid levels (0.13 mg/dL; 95% CI, 0.04 to 0.23), whereas losartan 5 0 mg/100 mg decreased them (-0.14 mg/dL; 95% CI, -0.24 to -0.04), and losar tan 50 mg/50 mg plus HCTZ 12.5 mg left them unchanged (0.06 mg/dL; 95% CI, -0.07 to 0.20). Conclusions: Losartan 50 mg/100 mg and candesartan 8 mg/16 mg were comparab le treatments in terms of blood pressure reduction. After titration, losart an 50 mg plus HCTZ 12.5 mg was superior to either candesartan 16 mg or losa rtan 100 mg in reducing hypertension. Losartan, but not candesartan, lowere d serum uric acid levels and attenuated the expected increase in uric acid levels with HCTZ 12.5 mg.