ACE Inhibitors, Statins Ineffective at Lowering Albumin Excretion

Combining ACE inhibitors with a statin was unsuccessful to change albumin-to-creatinine ratio in adolescent patients with T1D.

Loredana Marcovecchio, MD, PhD

According to the results of a new study, the use of an ACE inhibitor combined with a statin did not change the albumin-to-creatinine ratio in adolescent patients with type 1 diabetes (T1D).

The AdDIT Study Group looked at 4407 adolescents aged 10 to 16 years to find out if albumin excretion, which is known to increase during puberty and linked to the development of renal and cardiovascular disease, might be lowered by ACE inhibitors or statins. These drugs have not been studied fully in adolescent patients.

“The AdDIT trial indicates that treatment with ACE inhibitors and statins for 2 to 4 years in adolescents with type 1 diabetes is safe and can lead to short-term beneficial effects on lipids levels and reduce rates of microalbuminuria,” M. Loredana Marcovecchio, MD, PhD, and David Dunger, MD, MRCP, FRCP, from the Department of Paediatrics at University of Cambridge, Cambridge, UK, and coauthors of the study, told MD Magazine.

Among the study group of 4407 patients, 1287 (29.2%) had high albumin-to-creatinine ratios. The ratios were determined by urine samples obtained 6 months over the course of 2 to 4 years and expressed as the area under the curve. Of these patients, 443 were placed in a placebo-controlled trial of an ACE inhibitor and a statin that used a 2-by-2 factorial design.

In addition to changes in albumin excretion, researchers also looked at microalbuminuria, retinopathy progression, glomerular filtration rate, lipid levels, and cardiovascular risk factors (carotid intima-media thickness and levels of high-sensitivity C-reactive protein and asymmetric dimethylarginine). The study parameters also factored in age, sex, and duration of diabetes.

The study’s authors concluded that albumin excretion was not affected by the use of ACE inhibitors, statins, or a combination of both. There was a lower incidence of microalbuminuria than with placebo, but it was not considered significant (hazard ratio, 0.57; 95% confidence interval, 0.35-0.94).

The use of statins alone saw a reduction in levels of total, low-density lipoprotein, and non-high-density lipoprotein cholesterol, in triglycerides, and in ratios of apolipoproteins B and A1.

Neither drug seemed to affect carotid intima-media thickness retinopathy progression, changes in the glomerular filtration rate, or cardiovascular markers other than lipids.

“These effects could translate in a long-term reduction of vascular complications. Follow-up of the AdDIT cohort will provide invaluable information on the full benefits of statins and ACE inhibitors in relation to long-term complications,” Marcovecchio and Dunger added.

The patients were 75% compliant with their drug regimens, and all groups reported similar adverse effects.

The study was published in the New England Journal of Medicine on November 2.

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