NEJM 2001 Renoprotective Effect of Irbesartan on Diabetic Nephropathy PDF

The New England Journal of Medicine C o py r ig ht © 2 0 0 1 by t he Ma s s ac h u s e t t s Me d ic a l S o c ie t y V O L U ME 3 4 5 S E P T E M B E R 20, 2001...

The New England Journal of Medicine C o py r ig ht © 2 0 0 1 by t he Ma s s ac h u s e t t s Me d ic a l S o c ie t y V O L U ME 3 4 5 S E P T E M B E R 20, 2001 NUMB ER 12 RENOPROTECTIVE EFFECT OF THE ANGIOTENSIN-RECEPTOR ANTAGONIST IRBESARTAN IN PATIENTS WITH NEPHROPATHY DUE TO TYPE 2 DIABETES EDMUND J. LEWIS, M.D., LAWRENCE G. HUNSICKER, M.D., WILLIAM R. CLARKE, PH.D., TOMAS BERL, M.D., MARC A. POHL, M.D., JULIA B. LEWIS, M.D., EBERHARD RITZ, M.D., ROBERT C. ATKINS, M.D., RICHARD ROHDE, B.S., AND ITAMAR RAZ, M.D., FOR THE COLLABORATIVE STUDY GROUP* D ABSTRACT IABETES mellitus is increasing in preva- Background It is unknown whether either the an- lence worldwide and is currently estimat- giotensin-II–receptor blocker irbesartan or the cal- ed to affect more than 6.5 percent of the cium-channel blocker amlodipine slows the progres- population of the United States.1 Diabetes sion of nephropathy in patients with type 2 diabetes is the most common cause of end-stage renal disease independently of its capacity to lower the systemic in this country, accounting for 40 percent of cases.2 blood pressure. Although the inhibition of the effects of angiotensin Methods We randomly assigned 1715 hypertensive II has a beneficial effect in patients with nephropathy patients with nephropathy due to type 2 diabetes to caused by type 1 diabetes,3 no published study with treatment with irbesartan (300 mg daily), amlodipine (10 mg daily), or placebo. The target blood pressure definitive renal outcomes has addressed the issue of was 135/85 mm Hg or less in all groups. We compared renoprotection in patients with type 2 diabetes — a the groups with regard to the time to the primary population that differs substantially from patients with composite end point of a doubling of the base-line se- type 1 diabetes in terms of demographic characteris- rum creatinine concentration, the development of end- tics, metabolic features, and potential mechanisms of stage renal disease, or death from any cause. We also glomerular disease.4 Several studies have addressed compared them with regard to the time to a second- the positive effects of specific antihypertensive agents ary, cardiovascular composite end point. on cardiovascular morbidity and mortality within this Results The mean duration of follow-up was 2.6 population.5-8 years. Treatment with irbesartan was associated with We undertook the Irbesartan Diabetic Nephropathy a risk of the primary composite end point that was 20 Trial to determine whether the use of an angioten- percent lower than that in the placebo group (P=0.02) and 23 percent lower than that in the amlodipine sin-II–receptor blocker or a calcium-channel blocker group (P=0.006). The risk of a doubling of the serum would provide protection against the progression of creatinine concentration was 33 percent lower in the nephropathy due to type 2 diabetes beyond that at- irbesartan group than in the placebo group (P=0.003) tributable to the lowering of the blood pressure. We and 37 percent lower in the irbesartan group than in also compared the groups assigned to different ther- the amlodipine group (P