DIRECT (Diabetic Retinopathy Candesartan Trials) Program Study Group (Including: Bilous, Rudy, Chaturvedi, Nish, Sjølie, Anne Katrin, Fuller, John, Klein, Ronald, Orchard, Trevor, Porta, Massimo and Parving, Hans-Henrik). (2009) Effect of candesartan on microalbuminuria and albumin excretion rate in diabetes : three randomized trials. Annals of Internal Medicine, Vol.151 (No.1). pp. 11-20. ISSN 0003-4819

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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 µg/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 µg/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 ≥20 µg/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.

Primary Funding Source: AstraZeneca and Takeda.

Item Type:	Journal Article
Subjects:	R Medicine > R Medicine (General)
Divisions:	Faculty of Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Annals of Internal Medicine
Publisher:	American College of Physicians
ISSN:	0003-4819
Official Date:	7 July 2009
Dates:	Date Event 7 July 2009 Published
Volume:	Vol.151
Number:	No.1
Page Range:	pp. 11-20
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
URI:	http://wrap.warwick.ac.uk/id/eprint/45503

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