BACKGROUND: It is unknown whether either the angiotensin-II-receptor blocker irbesartan
or the calcium-channel blocker amlodipine slows the progression of nephropathy in
patients with type 2 diabetes independently of its capacity to lower the systemic
blood pressure. METHODS: We randomly assigned 1715 hypertensive patients with nephropathy
due to type 2 diabetes to treatment with irbesartan (300 mg daily), amlodipine (10
mg daily), or placebo. The target blood pressure was 135/85 mm Hg or less in all groups.
We compared the groups with regard to the time to the primary composite end point
of a doubling of the base-line serum creatinine concentration, the development of
end-stage renal disease, or death from any cause. We also compared them with regard
to the time to a secondary, cardiovascular composite end point. RESULTS: The mean
duration of follow-up was 2.6 years. Treatment with irbesartan was associated with
a risk of the primary composite end point that was 20 percent lower than that in the
placebo group (P=0.02) and 23 percent lower than that in the amlodipine group (P=0.006).
The risk of a doubling of the serum creatinine concentration was 33 percent lower
in the irbesartan group than in the placebo group (P=0.003) and 37 percent lower in
the irbesartan group than in the amlodipine group (P<0.001). Treatment with irbesartan
was associated with a relative risk of end-stage renal disease that was 23 percent
lower than that in both other groups (P=0.07 for both comparisons). These differences
were not explained by differences in the blood pressures that were achieved. The serum
creatinine concentration increased 24 percent more slowly in the irbesartan group
than in the placebo group (P=0.008) and 21 percent more slowly than in the amlodipine
group (P=0.02). There were no significant differences in the rates of death from any
cause or in the cardiovascular composite end point. CONCLUSIONS: The angiotensin-II-receptor
blocker irbesartan is effective in protecting against the progression of nephropathy
due to type 2 diabetes. This protection is independent of the reduction in blood pressure
it causes.
