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

Athanasios J. Manolis, Ehud Grossman, Bojan Jelakovic, Andrew Jacovides, David C. Bernhardi, Walter J. Cabrera, Luis A. Watanabe, Jaime Barragan, Norberto Matadamas, Alfred Mendiola, K. S. Woo, Jun R. Zhu, Agnes D. Mejia, Ton Bunt, Thomas Dumortier, Ronald D. Smith

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: The goal of this multicenter, double-blind, randomized, parallel-group study was to compare the effects of losartan potassium (hereafter referred to as losartan), candesartan cilexitil (hereafter referred to as candesartan), 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 weeks 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 losartan 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 <90 mm Hg were titrated as described, whereas patients achieving this goal continued with low-dose monotherapy. The single primary end point at 12 weeks tested the equivalence of the 2 monotherapy regimens, predefined as a maximum betweentreatment difference in the mean change from baseline trough SiDBP of 2.5 mm Hg. Results: At 12 weeks, changes m SiDBP/sitting systolic blood pressure (SiSBP) of -12.4/-14.4 mm Hg with losartan 50 mg/100 mg and -13.1/-15.8 mm Hg with candesartan 8 mg/16 mg demonstrated equivalence between the 2 monotherapy 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 significantly 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 (SiDBP and SiSBP, P = 0.001). During the last 6 weeks, patients whose regimen had been titrated to losartan 50 mg plus HCTZ 12.5 mg (n = 114) showed a greater reduction in SiDBP/SiSBP (-14.5/-18.7 mm Hg) than did those whose regimen 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 clinically meaningful (≥2.5-mm Hg) difference. All 3 treatments were well tolerated, with few patients experiencing drug-related adverse events (6.9% losartan 50 mg/100 mg, 7.5% candesartan 8 mg/16 mg, 3.0% losartan 50 mg/50 mg plus HCTZ 12.5 mg). Candesartan 8 mg/16 mg increased serum uric acid levels (0.13 mg/dL, 95% CI, 0.04 to 0.23), whereas losartan 50 mg/100 mg decreased them (-0.14 mg/dL; 95% CI, -0.24 to -0.04), and losartan 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 comparable treatments in terms of blood pressure reduction. After titration, losartan 50 mg plus HCTZ 12.5 mg was superior to either candesartan 16 mg or losartan 100 mg in reducing hypertension. Losartan, but not candesartan, lowered serum uric acid levels and attenuated the expected increase in uric acid levels with HCTZ 12.5 mg.

Original languageEnglish
Pages (from-to)1186-1203
Number of pages18
JournalClinical Therapeutics
Volume22
Issue number10
DOIs
StatePublished - 2000

Keywords

  • Angiotensin II antagonist
  • Antihypertensive therapy
  • Candesartan
  • Hydrochlorothiazide
  • Losartan

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