title: Dual blockade of the renin-angiotensin system compared with a 50% increase in the dose of angiotensin-converting enzyme inhibitor: effects on proteinuria and blood pressure.
abstract: BACKGROUND
  Several publications in the past 2 years have demonstrated that combined angiotensin-converting enzyme inhibitors (ACEI) and angiotensin-II receptor antagonist (AIIRA) are more effective in reducing blood pressure and proteinuria in patients with chronic renal disease than ACEI or AIIRA alone. This study compares the effect of increasing the ACEI dose by 50% with that of adding an AIIRA to a standard ACEI dose.
  
  
  METHODS
  This study was designed as part of a previous comparison of ACEI with ACEI plus candesartan. Directly after completion of the randomized intervention periods of that study, the dose of ACEI was increased by 50% in all patients. Proteinuria and blood pressure were compared in both groups of patients in the three periods, on standard ACEI, on ACEI plus candesartan and on a dose of ACEI increased by 50%.
  
  
  RESULTS
  No significant differences in the primary end-point proteinuria or secondary end-points were observed when the ACEI dose was increased by 50%. Proteinuria was 1.8 g in 24 h on candesartan and ACEI and 2.4 g in 24 h when the ACEI dose was increased by 50% (P<0.02). Systolic blood pressure was 126.6 mmHg on candesartan and ACEI and 134.47 mmHg when the ACEI dose was increased by 50% (P<0.002). Diastolic blood pressure, serum creatinine, urea and potassium were not different between groups.
  
  
  CONCLUSIONS
  Standard ACEI plus candesartan is more effective in reducing systolic blood pressure and proteinuria than a 50% increase in ACEI dose. This has implications for the prevention of renal failure in chronic renal disease.
authors.affiliation: Epworth Hospital, Richmond, Victoria, Australia. priscillk@epworth.org.au
authors.forename: Priscilla
authors.initials: P
authors.lastname: Kincaid-Smith
authors.forename: Kenneth F
authors.initials: KF
authors.lastname: Fairley
authors.forename: David
authors.initials: D
authors.lastname: Packham
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007676:Kidney Failure, Chronic / Q000150:complications / Q000188:drug therapy*; D011507:Proteinuria / Q000188:drug therapy; D012084:Renin-Angiotensin System / Q000187:drug effects*; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; C081643:candesartan