Angiotensin-II receptor blockers delay renal disease in type 2 diabetics

By Anthony J. Brown, MD

WESTPORT, CT (Reuters Health) – Angiotensin-II receptor blockers (ARBs) offer significant renoprotective effects that can delay the progression of nephropathy in patients with type 2 diabetes, according to findings from three studies published in the September 20th issue of The New England Journal of Medicine.

An international team led by Dr. Edmund J. Lewis, from Rush Medical Center in Chicago, studied the renoprotective effects of irbesartan in 1715 hypertensive patients with nephropathy due to type 2 diabetes. The subjects were randomized to receive 300 mg of irbesartan, 10 mg of amlodipine, or placebo once daily. The goal blood pressure in all groups was 135/85 mm Hg or less. The patients were followed for 2.6 years on average.

Irbesartan-treated patients were significantly less likely than others to experience a doubling of serum creatinine levels, the authors note. In addition, the irbesartan group's risk of end-stage renal disease was about 20% lower than that of the other groups. Irbesartan's renoprotective effects were independent of its ability to reduce blood pressure, the researchers point out.

"Irbesartan produces an extremely important delay in progression of renal disease," Dr. Lewis told Reuters Health. "Our findings also indicate that it is protective against congestive heart failure," he said. "I expect ARBs will have an enormous impact on the incidence of end-stage renal disease."

Dr. Hans-Henrik Parving, from the Steno Diabetes Center in Gentofte, Denmark, and colleagues performed a similar study involving hypertensive type 2 diabetics with microalbuminuria. In this trial, 590 patients were randomized to receive irbesartan at a dose of 150 or 300 mg/day or placebo.

Irbesartan-treated patients were less likely to develop nephropathy than placebo-treated patients, the authors found. The association was noted in both irbesartan groups, but it reached statistical significance only in the higher-dose group (p < 0.001). While irbesartan treatment did produce a significant decrease in systolic blood pressures, its renoprotective effects were once again independent of its blood pressure-lowering ability.

In the other study, Dr. Barry M. Brenner, from Brigham and Women's Hospital in Boston, and colleagues assessed the benefits of losartan in 1513 patients with type 2 diabetes and nephropathy. The subjects were randomized to receive 50 to 100 mg of losartan or placebo once daily.

Similar to the findings with irbesartan, losartan treatment was associated with a reduced incidence of serum creatinine doubling and with a delay in progression to end-stage renal disease. Losartan treatment was associated with a significant improvement in proteinuria levels. The researchers also found that losartan treatment was linked to a lower rate of first hospitalization for heart failure.

In a related editorial, Dr. Thomas H. Hostetter, from the National Institutes of Health in Bethesda, Maryland, comments on the three trials and on the management of renal disease in type 2 diabetics.

"These studies provide useful information, but they would have been even more meaningful if they had included an angiotensin-converting enzyme inhibitor comparison group," Dr. Hostetter told Reuters Health. "My speculation was that it was financially disadvantageous to include such a group," he added.

"If I was presented with a type 2 diabetic patient with early signs of renal failure I would aggressively control their blood pressure," Dr. Hostetter stated. "I would use an ACE inhibitor based on findings from a fair number of smaller studies which suggest that they are just as good as ARBs." Aside from ACE inhibitors being less expensive, the only real distinguishing characteristic between them and ARBs is their side effect profiles, he said.

"Unfortunately, probably less than a third of patients who should be treated with an ACE inhibitor or an ARB actually are treated," Dr. Hostetter pointed out.

N Engl J Med 2001;345:851-878,910-911.

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