Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials

Rudy Bilous, Nish Chaturvedi, Anne Katrin Sjølie, John Fuller, Ronald Klein, Trevor Orchard, Massimo Porta, Hans-Henrik Parving

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

Udgivelsesdato: 2009-Jul-7
OriginalsprogEngelsk
TidsskriftAnnals of Internal Medicine
Vol/bind151
Udgave nummer1
Sider (fra-til)11-20, W3-4
ISSN0003-4819
StatusUdgivet - 7. jul. 2009

Fingeraftryk

Albumins
Albuminuria
Type 2 Diabetes Mellitus
Placebos
Secondary Care Centers
Research Personnel
Angiotensin Receptor Antagonists
Diabetic Retinopathy
Caregivers
Kidney
Incidence

Citer dette

Bilous, R., Chaturvedi, N., Sjølie, A. K., Fuller, J., Klein, R., Orchard, T., ... Parving, H-H. (2009). Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. Annals of Internal Medicine, 151(1), 11-20, W3-4.
Bilous, Rudy ; Chaturvedi, Nish ; Sjølie, Anne Katrin ; Fuller, John ; Klein, Ronald ; Orchard, Trevor ; Porta, Massimo ; Parving, Hans-Henrik. / Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. I: Annals of Internal Medicine. 2009 ; Bind 151, Nr. 1. s. 11-20, W3-4.
@article{01341cc00a5311dfaefb000ea68e967b,
title = "Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials",
abstract = "BACKGROUND: Microalbuminuria in diabetes is strongly predictive of nephropathy, end-stage renal disease, and premature cardiovascular morbidity and mortality. Effective preventive therapies are therefore a clinical priority. OBJECTIVE: To determine whether the angiotensin-receptor blocker candesartan compared with placebo affects microalbuminuria incidence or rate of change in albuminuria in type 1 and type 2 diabetes. DESIGN: 3 randomized trials of the DIRECT (Diabetic Retinopathy Candesartan Trials) Program. SETTING: 309 secondary care centers. PATIENTS: 3326 and 1905 patients with type 1 and type 2 diabetes, respectively. Most were normotensive, and all had normoalbuminuria (median urinary albumin excretion rate, 5.0 microg/min). INTERVENTION: Candesartan, 16 mg/d increasing to 32 mg/d, versus placebo. Assignment was done centrally using an interactive voice-response system. Patients, caregivers, and researchers were blinded to treatment assignment. During a median follow-up of 4.7 years, 793 patients discontinued therapy and 63 were lost to follow-up. MEASUREMENTS: Urinary albumin excretion rate, assessed annually by 2 overnight collections; if it was 20 microg/min or greater, then 2 further collections were done. The primary end point was new microalbuminuria (3 or 4 collections of urinary albumin excretion rate >or=20 microg/min). The secondary end point was rate of change in albuminuria. RESULTS: Individual and pooled results of the 3 trials showed that candesartan had little effect on risk for microalbuminuria (pooled hazard ratio, 0.95 [95{\%} CI, 0.78 to 1.16]; P = 0.60). Pooled results showed that the annual rate of change in albuminuria was 5.53{\%} lower (CI, 0.73{\%} to 10.14{\%}; P = 0.024) with candesartan than with placebo. LIMITATIONS: Investigators recruited mainly normotensive patients or patients with well-controlled hypertension who were at low overall vascular risk, which resulted in a low rate of microalbuminuria. Studies were powered for retinal and not renal end points. CONCLUSION: Candesartan, 32 mg/d, for 4.7 years did not prevent microalbuminuria in mainly normotensive patients with type 1 or type 2 diabetes.",
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author = "Rudy Bilous and Nish Chaturvedi and Sj{\o}lie, {Anne Katrin} and John Fuller and Ronald Klein and Trevor Orchard and Massimo Porta and Hans-Henrik Parving",
year = "2009",
month = "7",
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language = "English",
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pages = "11--20, W3--4",
journal = "Annals of Internal Medicine",
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publisher = "American College of Physicians",
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Bilous, R, Chaturvedi, N, Sjølie, AK, Fuller, J, Klein, R, Orchard, T, Porta, M & Parving, H-H 2009, 'Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials', Annals of Internal Medicine, bind 151, nr. 1, s. 11-20, W3-4.

Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. / Bilous, Rudy; Chaturvedi, Nish; Sjølie, Anne Katrin; Fuller, John; Klein, Ronald; Orchard, Trevor; Porta, Massimo; Parving, Hans-Henrik.

I: Annals of Internal Medicine, Bind 151, Nr. 1, 07.07.2009, s. 11-20, W3-4.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials

AU - Bilous, Rudy

AU - Chaturvedi, Nish

AU - Sjølie, Anne Katrin

AU - Fuller, John

AU - Klein, Ronald

AU - Orchard, Trevor

AU - Porta, Massimo

AU - Parving, Hans-Henrik

PY - 2009/7/7

Y1 - 2009/7/7

N2 - BACKGROUND: Microalbuminuria in diabetes is strongly predictive of nephropathy, end-stage renal disease, and premature cardiovascular morbidity and mortality. Effective preventive therapies are therefore a clinical priority. OBJECTIVE: To determine whether the angiotensin-receptor blocker candesartan compared with placebo affects microalbuminuria incidence or rate of change in albuminuria in type 1 and type 2 diabetes. DESIGN: 3 randomized trials of the DIRECT (Diabetic Retinopathy Candesartan Trials) Program. SETTING: 309 secondary care centers. PATIENTS: 3326 and 1905 patients with type 1 and type 2 diabetes, respectively. Most were normotensive, and all had normoalbuminuria (median urinary albumin excretion rate, 5.0 microg/min). INTERVENTION: Candesartan, 16 mg/d increasing to 32 mg/d, versus placebo. Assignment was done centrally using an interactive voice-response system. Patients, caregivers, and researchers were blinded to treatment assignment. During a median follow-up of 4.7 years, 793 patients discontinued therapy and 63 were lost to follow-up. MEASUREMENTS: Urinary albumin excretion rate, assessed annually by 2 overnight collections; if it was 20 microg/min or greater, then 2 further collections were done. The primary end point was new microalbuminuria (3 or 4 collections of urinary albumin excretion rate >or=20 microg/min). The secondary end point was rate of change in albuminuria. RESULTS: Individual and pooled results of the 3 trials showed that candesartan had little effect on risk for microalbuminuria (pooled hazard ratio, 0.95 [95% CI, 0.78 to 1.16]; P = 0.60). Pooled results showed that the annual rate of change in albuminuria was 5.53% lower (CI, 0.73% to 10.14%; P = 0.024) with candesartan than with placebo. LIMITATIONS: Investigators recruited mainly normotensive patients or patients with well-controlled hypertension who were at low overall vascular risk, which resulted in a low rate of microalbuminuria. Studies were powered for retinal and not renal end points. CONCLUSION: Candesartan, 32 mg/d, for 4.7 years did not prevent microalbuminuria in mainly normotensive patients with type 1 or type 2 diabetes.

AB - BACKGROUND: Microalbuminuria in diabetes is strongly predictive of nephropathy, end-stage renal disease, and premature cardiovascular morbidity and mortality. Effective preventive therapies are therefore a clinical priority. OBJECTIVE: To determine whether the angiotensin-receptor blocker candesartan compared with placebo affects microalbuminuria incidence or rate of change in albuminuria in type 1 and type 2 diabetes. DESIGN: 3 randomized trials of the DIRECT (Diabetic Retinopathy Candesartan Trials) Program. SETTING: 309 secondary care centers. PATIENTS: 3326 and 1905 patients with type 1 and type 2 diabetes, respectively. Most were normotensive, and all had normoalbuminuria (median urinary albumin excretion rate, 5.0 microg/min). INTERVENTION: Candesartan, 16 mg/d increasing to 32 mg/d, versus placebo. Assignment was done centrally using an interactive voice-response system. Patients, caregivers, and researchers were blinded to treatment assignment. During a median follow-up of 4.7 years, 793 patients discontinued therapy and 63 were lost to follow-up. MEASUREMENTS: Urinary albumin excretion rate, assessed annually by 2 overnight collections; if it was 20 microg/min or greater, then 2 further collections were done. The primary end point was new microalbuminuria (3 or 4 collections of urinary albumin excretion rate >or=20 microg/min). The secondary end point was rate of change in albuminuria. RESULTS: Individual and pooled results of the 3 trials showed that candesartan had little effect on risk for microalbuminuria (pooled hazard ratio, 0.95 [95% CI, 0.78 to 1.16]; P = 0.60). Pooled results showed that the annual rate of change in albuminuria was 5.53% lower (CI, 0.73% to 10.14%; P = 0.024) with candesartan than with placebo. LIMITATIONS: Investigators recruited mainly normotensive patients or patients with well-controlled hypertension who were at low overall vascular risk, which resulted in a low rate of microalbuminuria. Studies were powered for retinal and not renal end points. CONCLUSION: Candesartan, 32 mg/d, for 4.7 years did not prevent microalbuminuria in mainly normotensive patients with type 1 or type 2 diabetes.

KW - Adult

KW - Aged

KW - Albuminuria

KW - Angiotensin II Type 1 Receptor Blockers

KW - Benzimidazoles

KW - Diabetes Mellitus, Type 1

KW - Diabetes Mellitus, Type 2

KW - Diabetic Nephropathies

KW - Double-Blind Method

KW - Female

KW - Humans

KW - Hyperkalemia

KW - Male

KW - Middle Aged

KW - Tetrazoles

KW - Young Adult

M3 - Journal article

VL - 151

SP - 11-20, W3-4

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

IS - 1

ER -

Bilous R, Chaturvedi N, Sjølie AK, Fuller J, Klein R, Orchard T et al. Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes: three randomized trials. Annals of Internal Medicine. 2009 jul 7;151(1):11-20, W3-4.