title: Effects of combination treatment with losartan and trandolapril on office and ambulatory blood pressures in non-diabetic renal disease: a COOPERATE-ABP substudy.
abstract: BACKGROUND
  In the COOPERATE trial, the combination treatment of the angiotensin-II receptor blocker losartan and the angiotensin-converting-enzyme inhibitor trandolapril significantly retarded progression of non-diabetic kidney disease compared with each monotherapy. The benefit could be greatly attributable to the potent reduction of proteinuria, because the three treatment groups showed the same reductions of office blood pressure (OBP). Ambulatory blood pressure (ABP) is reported to be better than OBP in predicting progression of kidney disease.
  
  
  METHODS
  Ninety-two patients enrolled in the COOPERATE trial underwent 24-hour ABP monitoring at randomization and at month 6, year 1, year 2 and year 3 on randomized treatment.
  
  
  RESULTS
  Both OBP and ABP were similarly reduced among the three groups at all measurement points (p = NS) and throughout the whole study period (p = NS). No significant correlation between the change in 24-hour ABP and the change in proteinuria was seen (p = NS). A Cox-multivariable analysis showed that covariates affecting the renal outcomes (a doubling serum-Cr level and/or end-stage renal failure) were the change in proteinuria (hazard ratio 0.49, 95% CI 0.34-0.78, p = 0.01) and treatments (0.58, 0.45-0.99, 0.03), but not 24-hour ABP (0.98, 0.89-2.01, 0.17).
  
  
  CONCLUSIONS
  The better renoprotective effect of the combination treatment is attributed to BP-independent mechanisms by more complete renin-angiotensin system blockade.
authors.affiliation: Kaikou-Kai Central Clinic, Division Nephrology, Nagaya Kyoritsu Hospital, Nagoy, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Nakao
authors.forename: Hachiro
authors.initials: H
authors.lastname: Seno
authors.forename: Hirotake
authors.initials: H
authors.lastname: Kasuga
authors.forename: Takanobu
authors.initials: T
authors.lastname: Toriyama
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Kawahara
authors.forename: Masafumi
authors.initials: M
authors.lastname: Fukagawa
mesh_terms: D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects*; D018660:Blood Pressure Monitoring, Ambulatory; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage*; D007674:Kidney Diseases / Q000517:prevention & control*; D019808:Losartan / Q000008:administration & dosage*; D008297:Male; D009819:Office Visits; D013997:Time Factors
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C052035:trandolapril; D019808:Losartan