title: Effect of dual blockade of the renin-angiotensin system on the progression of type 2 diabetic nephropathy: a randomized trial.
abstract: BACKGROUND
  Blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers has been shown to lessen the rate of decrease in glomerular filtration rate in patients with diabetic nephropathy.
  
  
  METHODS
  A multicenter open-label randomized controlled trial to compare the efficacy of combining the angiotensin-converting enzyme inhibitor lisinopril and the angiotensin II receptor blocker irbesartan with that of each drug in monotherapy (at both high and equipotent doses) in slowing the progression of type 2 diabetic nephropathy.
  
  
  METHODS
  133 patients with type 2 diabetic nephropathy (age, 66 ± 8 years; 76% men) from 17 centers in Spain.
  
  
  METHODS
  Patients were randomly assigned (1:1:2) to lisinopril (n = 35), irbesartan (n = 28), or the combination of both (n = 70).
  
  
  RESULTS
  The primary composite outcome was a >50% increase in baseline serum creatinine level, end-stage renal disease, or death.
  
  
  RESULTS
  Baseline values for mean estimated glomerular filtration rate and blood pressure were 49 ± 21 mL/min/1.73 m(2) and 153 ± 19/81 ± 11 mm Hg. Mean geometric baseline proteinuria was protein excretion of 1.32 (95% CI, 1.10-1.62) g/g creatinine. After a median follow-up of 32 months, 21 (30%) patients in the combination group, 10 (29%) in the lisinopril group, and 8 (29%) in the irbesartan group reached the primary outcome. HRs were 0.96 (95% CI, 0.44-2.05; P = 0.9) and 0.90 (95% CI, 0.39-2.02; P = 0.8) for the combination versus the lisinopril and irbesartan groups, respectively. There were no significant differences in proteinuria reduction or blood pressure control between groups. The number of adverse events, including hyperkalemia, was similar in all 3 groups.
  
  
  CONCLUSIONS
  The study was not double blind. The sample size studied was small.
  
  
  CONCLUSIONS
  We were unable to show a benefit of the combination of lisinopril and irbesartan compared to either agent alone at optimal high doses on the risk of progression of type 2 diabetic nephropathy.
authors.affiliation: Hospital Fundación de Alcorcón, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Fernandez Juarez
authors.forename: José
authors.initials: J
authors.lastname: Luño
authors.forename: Vicente
authors.initials: V
authors.lastname: Barrio
authors.forename: Soledad García
authors.initials: SG
authors.lastname: de Vinuesa
authors.forename: Manuel
authors.initials: M
authors.lastname: Praga
authors.forename: Marian
authors.initials: M
authors.lastname: Goicoechea
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: Javier
authors.initials: J
authors.lastname: Nieto
authors.forename: Francisco
authors.initials: F
authors.lastname: Fernández Vega
authors.forename: Ana
authors.initials: A
authors.lastname: Tato
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gutierrez
mesh_terms: D000368:Aged; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D000077405:Irbesartan; D017706:Lisinopril / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D013777:Tetrazoles; D017706:Lisinopril; D000077405:Irbesartan