Renoprotective Effects of the Angiotensin-Receptor Antagonist Irbesartan in Patients With Nephropathy Due to Type 2 Diabetes - Renoprotective Effects of the Angiotensin-Receptor Antagonist Irbesartan in Patients With Nephropathy Due to Type 2 Diabetes
Renoprotective Effects of the Angiotensin-Receptor Antagonist Irbesartan in Patients With Nephropathy Due to Type 2 Diabetes.
Does the angiotensin-II receptor blocker irbesartan or the calcium channel blocker amlodipine slow the progression of diabetic nephropathy independent of blood pressure lowering effects?
Patients Enrolled: 1715
1715 hypertensive diabetics age 30–70 years with proteinuria (> 900 mg/24hrs) were randomized to placebo, irbesartan (300mg/d) or amlodipine (10mg/d). Target BP was 135/85 mm Hg or less in each group. The assigned agent could be supplemented with any non-ACE-related antihypertensive agents. The primary composite end point was a doubling of the baseline creatinine, onset of end-stage renal disease or death. The secondary end point was the composite of major cardiovascular events including stroke and amputation.
The average age was 59 years, 67% male, 58% insulin dependent, 28% had cardiovascular disease and mean values for clinical variables were: BMI 30.5kg/m2, BP 160/87 mm Hg, creatinine 1.67 mg/dL, urine protein 2.9 g/hrs and glycosylated Hgb 8.2%. Average follow-up was 2.6 years. Irbestartan therapy was associated with a 20% reduction in the primary end point compared to placebo (p=0.02) and 23% less than amlodipine (p = 0.006). The mean rate of change in serum creatinine was 0.45 mg/dL/year on irbesarten, 0.57mg/dL/year on amlodipine and 0.59mg/dL/year on placebo. Proteinuria was reduced by an average of 33% with irbesartan compared to 6% with amlodipine and 10% with placebo. The results were independent of the blood pressure lowering which was similar with irbesartan and amlodipine and each slightly greater than placebo. There were no between group differences in deaths or composite CV events, but compared to placebo, there were 23% less hospitalizations for CHF with irbesartan and 41% less non-fatal MIs with amlodipine.
The angiotensin-II receptor blocker irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. The protection is independent of the reduction in blood pressure.
Unfortunately this study does not help the clinician decide between an ARB or ACEi in diabetics with renal failure and proteinuria, which is the more important question. See the discussion in Editors Comments that follows.
1. Lewis EJ, Hunsicker LG, Clarke WR, et al. for the Collaborative Study Group. N Engl J Med 2001;345:851-60.
Keywords: Angiotensin Receptor Antagonists, Stroke, Insulin, Follow-Up Studies, Kidney Failure, Chronic, Diabetes Mellitus, Type 2, Proteinuria, Diabetic Nephropathies, Creatinine, Tetrazoles, Calcium Channel Blockers, Biphenyl Compounds, Body Mass Index, Amlodipine, Hypertension
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