Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy

Background Diabetic nephropathy is the leading cause of end-stage renal dis ease. Interruption of the renin angiotensin system slows the progression of renal disease in patients with type 1 diabetes, but similar data are not a vailable for patients with type 2, the most common form of diabetes. We ass essed the role of the angiotensin-II receptor antagonist losartan in patien ts with type 2 diabetes and nephropathy. Methods A total of 1513 patients were enrolled in this randomized, double-b lind study comparing losartan (50 to 100 mg once daily) with placebo, both taken in addition to conventional antihypertensive treatment (calcium-chann el antagonists, diuretics, alpha-blockers, beta-blockers, and centrally act ing agents), for a mean of 3.4 years. The primary outcome was the composite of a doubling of the base-line serum creatinine concentration, end-stage r enal disease, or death. Secondary end points included a composite of morbid ity and mortality from cardiovascular causes, proteinuria, and the rate of progression of renal disease. Results A total of 327 patients in the losartan group reached the primary e nd point, as compared with 359 in the placebo group (risk reduction, 16 per cent; P=0.02). Losartan reduced the incidence of a doubling of the serum cr eatinine concentration ( risk reduction, 25 percent; P=0.006) and end-stage renal disease ( risk reduction, 28 percent; P=0.002) but had no effect on the rate of death. The benefit exceeded that attributable to changes in blo od pressure. The composite of morbidity and mortality from cardiovascular c auses was similar in the two groups, although the rate of first hospitaliza tion for heart failure was significantly lower with losartan ( risk reducti on, 32 percent; P=0.005). The level of proteinuria declined by 35 percent w ith losartan ( P<0.001 for the comparison with placebo). Conclusions Losartan conferred significant renal benefits in patients with type 2 diabetes and nephropathy, and it was generally well tolerated. (N En gl J Med 2001; 345: 861-9.) Copyright (C) 2001 Massachusetts Medical Societ y.