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.
The role of angiotensin-receptor blockers in the primary prevention of microalbuminuria is unclear.
These 3 randomized trials assessed whether candesartan prevented microalbuminuria more than placebo in adults with normoalbuminuria. All participants had either type 1 or type 2 diabetes, and most were normotensive. Individual and pooled results of the 3 trials showed similar rates of development of microalbuminuria with candesartan or placebo over a 4- to 5-year follow-up.
Renin–angiotensin system blockade with an angiotensin-receptor blocker did not prevent microalbuminuria in mostly normotensive people with diabetes.
Number of patients who did not complete renal functional assessments includes those who died or were lost to follow-up. DIRECT = Diabetic Retinopathy Candesartan Trial; MA = microalbuminuria.
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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. Ann Intern Med. 2009;151:11-20. doi: 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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