Marcovecchio ML, et al. - In this study, researchers tested their hypothesis that adolescents with high levels of albumin excretion might benefit from angiotensin-converting–enzyme (ACE) inhibitors and statins, drugs that have not been fully evaluated in adolescents. Findings revealed no utility of an ACE inhibitor and a statin for changing the albumin-to-creatinine ratio over time.

Methods

• In this study, 4407 adolescents with type 1 diabetes between the ages of 10 and 16 years of age were screened and 1287 with values in the upper third of the albumin-to-creatinine ratios were identified.
• Researchers randomly assigned 443 patients in a placebo-controlled trial of an ACE inhibitor and a statin with the use of a 2-by-2 factorial design minimizing differences in baseline characteristics such as age, sex, and duration of diabetes.
• For both interventions, the primary outcome was the change in albumin excretion, assessed in accordance to the albumin-to-creatinine ratio calculated from three early-morning urine samples obtained every 6 months over 2 to 4 years, and expressed as the area under the curve.
• For this study, key secondary outcomes assessed were the development of microalbuminuria, progression of retinopathy, changes in the glomerular filtration rate, lipid levels, and measures of cardiovascular risk (carotid intima–media thickness and levels of high-sensitivity C-reactive protein and asymmetric dimethylarginine).

Results

• ACE inhibitor therapy, statin therapy, or the combination of the two did not affected the primary outcome.
• Compared to the use of placeo, the use of an ACE inhibitor was associated with a lower incidence of microalbuminuria; in the context of negative findings for the primary outcome and statistical analysis plan, this lower incidence was not considered significant (hazard ratio, 0.57; 95% confidence interval, 0.35 to 0.94).
• In this study, statin use led to marked reductions in total, low-density lipoprotein, and non–high-density lipoprotein cholesterol levels, in triglyceride levels, and in the ratio of apolipoprotein B to apolipoprotein A1, whereas neither drug had significant effects on carotid intima–media thickness, other cardiovascular markers, the glomerular filtration rate, or progression of retinopathy.
• Across the groups, overall adherence to the drug regimen was 75%, and serious adverse events were similar.