title: Combining blockers of the renin-angiotensin system or increasing the dose of an angiotensin II receptor antagonist in proteinuric patients: a randomized triple-crossover study.
abstract: OBJECTIVE
  The goal of this study was to investigate whether increasing the dose of an angiotensin II receptor blocker (ARB) provides as much benefits as combining the ARB with an angiotensin-converting enzyme inhibitor (ACEI) in terms of blood pressure (BP) control and urinary albumin excretion (UAE) in hypertensive patients with a proteinuria.
  
  
  METHODS
  We enrolled 20 hypertensive patients with proteinuric nephropathies and a reduced renal function in a randomized, 12-month, triple-crossover, prospective, open-label study to compare the effects of a regular dose of losartan (Los 100 mg q.d., LOS100) vs. a high dose of losartan (Los 100 mg b.i.d., LOS200) vs. losartan 100 mg q.d. associated with lisinopril 20 mg q.d. (LOS100 + LIS20). Each treatment was given for 8 weeks with a 4-week initial run-in period and 2 weeks of washout between each treatment phases. 24 h UAE and ambulatory BP were measured during the running phase and at the end of each treatment period.
  
  
  RESULTS
  Compared to pretreatment, 24 h SBP and DBP were reduced by 10/5 ± 7/4 mmHg with LOS100 (P = 0.023 vs. baseline) and, respectively, 13/6 ± 12/5 mmHg with LOS200 (P = 0.011) and 19/9 ± 15/8 mmHg with LOS100 + LIS20 (P < 0.01). UAE decreased significantly with LOS100 and to an even greater degree with LOS200 and LOS100 + LIS20 (P < 0.01 vs. baseline for both and P = 0.032, LOS100 + LIS20 vs. LOS200). The combination had a greater impact in patients with a high baseline proteinuria as suggested by a nonparallel leftward shift of the relationship between the changes in UAE induced by the combination and those induced by LOS200. The high dose of losartan was better tolerated than the combination.
  
  
  CONCLUSIONS
  Increasing the dose of losartan from 100 mg once daily to 100 mg twice a day enables to obtain a greater decrease in BP and proteinuria and is better tolerated than combining the ARB with lisinopril, though the high dose appears to be slightly less effective than the combination in patients with a marked proteinuria.
authors.affiliation: Service of Nephrology and Hypertension, Department of Medicine, CHUV, Lausanne, Switzerland.
authors.forename: Pascal
authors.initials: P
authors.lastname: Meier
authors.forename: Marc P
authors.initials: MP
authors.lastname: Maillard
authors.forename: Jacqueline R
authors.initials: JR
authors.lastname: Meier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Tremblay
authors.forename: Thierry
authors.initials: T
authors.lastname: Gauthier
authors.forename: Michel
authors.initials: M
authors.lastname: Burnier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000188:drug therapy* / Q000503:physiopathology; D012084:Renin-Angiotensin System; D055815:Young Adult
chemical_list: D057911:Angiotensin Receptor Antagonists