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Using Angiotensin Receptor Blockers for Renal Protection
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Am Fam Physician. 2002 Mar 1;65(5):963.
The renal protective effects of angiotensin blockade are well known but have been established mainly in trials using angiotensin-converting enzyme inhibitors in patients with type 1 diabetes. Lewis and colleagues conducted a prospective, randomized, double-blind trial comparing the effect of irbesartan, an angiotensin receptor blocker, with that of amlodipine and placebo in slowing the progression of diabetic renal disease.
The study consisted of 1,715 patients who were enrolled at more than 200 clinical sites. Eligible patients had type 2 diabetes, hypertension, and at least 900 mg of proteinuria in a 24-hour specimen. In addition to the randomly assigned study medication, patients were allowed to use antihypertensive drugs from other classes, with a target blood pressure control of 135/85 mm Hg or less. Study subjects were followed for two years and assessed for a number of outcomes, including doubling of the baseline serum creatinine level, onset of end-stage renal disease (serum creatinine level of at least 6.0 mg per dL [458 μmol per L] or use of dialysis), death from any cause, and a number of cardiovascular morbidities.
Blacks constituted about 13 percent of trial participants and approximately 34 percent of the study subjects were women. The majority of patients already had diabetic retinopathy in addition to proteinuria, and the average serum creatinine level at study onset was about 1.7 mg per dL (130 μmol per L). Blood pressure control improved during the trial in all three groups, with no clinically significant differences. Glycemic control, determined by measurement of glycosylated hemoglobin levels, also did not differ significantly.
After two years of follow-up, amlodipine was found to be no better than placebo in preventing a doubling of the serum creatinine level, onset of end-stage renal disease, or death. Irbesartan reduced the cumulative risk of these events by 20 percent compared with placebo. The authors did not provide the actual number of events, so the absolute risk reduction could not be calculated.
No significant differences were noted in cardiovascular outcomes among the three treatment groups. The improved renal outcomes in the irbesartan group were independent of the blood-pressure–lowering effects of the medication. Proteinuria was reduced by an average of 33 percent in patients taking irbesartan, versus a 10 percent reduction with placebo and a 6 percent reduction with amlodipine. No significant adverse effects occurred with irbesartan.
The authors conclude that irbesartan is better than amlodipine and placebo in slowing the progression of diabetic nephropathy.
Lewis EJ, et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. September 20, 2001;345:851–60.
Copyright © 2002 by the American Academy of Family Physicians.
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