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Enalapril, losartan treatment delayed progression of retinopathy in patients with type 1 diabetes
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Early blockade of the renin–angiotensin system with two antihypertensive medications — enalapril and losartan — delayed progression of retinopathy in more than 65% of patients with type 1 diabetes in the Renin–Angiotensin System Study.
In the multicenter, randomized, controlled trial, researchers randomly assigned 253 normotensive patients with type 1 diabetes and normoalbuminuria to daily losartan 100 mg (Cozaar, Merck) enalapril 20 mg (Vasotec, Merck) or placebo for five years.
The researchers measured blood pressure, albumin excretion rate, HbA1c levels and pill counts quarterly; glomerular filtration rate was assessed annually. Ninety-percent of the study population had a renal biopsy at baseline and at five years.
Progression to diabetic retinopathy
At baseline, 9% of patients had moderate-to-severe nonproliferative diabetic retinopathy, 18% had early nonproliferative retinopathy, 34% had no diabetic retinopathy and 40% had minimal nonproliferative retinopathy.
Administration of enalapril or losartan did not protect the participants’ kidneys from damage or from losing function.
During five years, the primary endpoint — changes in mesangial fractional volume per glomerulus — did not differ significantly between the placebo (0.016 units), enalapril (P=0.38) or losartan groups (P=0.26).
Five-year cumulative incidence of microalbuminuria was 17% in the losartan group (P=.01), 6% in the placebo group and 4% in the enalapril group (P=.96).
The odds for retinopathy progression by two steps or more was decreased by 65% in the enalapril group when compared with placebo (OR=0.35) and by 70% in the losartan group (OR=0.30).
“Given the current status of our ability to predict the risk for nephropathy, blockade of the renin–angiotensin system for the primary prevention of diabetic nephropathy in patients with type 1 diabetes is not supported by the present evidence,” the researchers wrote. “In contrast, we found beneficial effects of the angiotensin-converting–enzyme inhibitor enalapril and the angiotensin-receptor blocker losartan in reducing the risk for progression of diabetic retinopathy.”
Chronic cough occurred in 12 patients assigned to enalapril, six assigned to losartan and four patients assigned to placebo. Three biopsy-related serious adverse events occurred during the study period, but were completely resolved.
Mauer M. N Engl J Med. 2009;361: 40–51.