Rudy Bilous, MD; Nish Chaturvedi, MD; Anne Katrin Sjølie, MD; John Fuller, MD; Ronald Klein, MD; Trevor Orchard, MD; Massimo Porta, MD; Hans-Henrik Parving, MD
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.
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.
3 randomized trials of the DIRECT (Diabetic Retinopathy Candesartan Trials) Program.
309 secondary care centers.
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 Âµg/min).
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.
Urinary albumin excretion rate, assessed annually by 2 overnight collections; if it was 20 Âµg/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 â‰¥20 Âµg/min). The secondary end point was rate of change in albuminuria.
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]; PÂ = 0.60). Pooled results showed that the annual rate of change in albuminuria was 5.53% lower (CI, 0.73% to 10.14%; PÂ = 0.024) with candesartan than with placebo.
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.
Candesartan, 32 mg/d, for 4.7 years did not prevent microalbuminuria in mainly normotensive patients with type 1 or type 2 diabetes.
AstraZeneca and Takeda.
Bilous R, Chaturvedi N, Sjølie AK, et al. Effect of Candesartan on Microalbuminuria and Albumin Excretion Rate in Diabetes: Three Randomized Trials. Ann Intern Med. 2009;151:11–20. doi: https://doi.org/10.7326/0003-4819-151-1-200907070-00120
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Published: Ann Intern Med. 2009;151(1):11-20.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism, Hypertension.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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