[Effect of losartan on renal and cardiovascular complications of patients with type 2 diabetes and nephropathy]

Abstract

Introduction: Diabetic nephropathy is the leading cause of end-stage renal disease. Interruption of the renin-angiotensin system slows the progression of renal disease in type 1 diabetic patients, but similar data are not available for type 2, the most common form of diabetes. We assessed the role of the angiotensin II receptor antagonist, losartan, in type 2 diabetic patients with nephropathy.

Material and methods: One thousand five hundred and thirteen patients were enrolled in this randomised, placebo-controlled study of losartan (50 to 100 mg, once daily) or placebo, in addition to conventional antihypertensive treatment (calcium antagonists, diuretics, alpha- and beta-blockers, centrally acting agents) for a mean of 3.4 years. The primary outcome was the composite of doubling of baseline serum creatinine, end-stage renal disease, or death. Secondary end points included a composite of cardiovascular morbidity and mortality, proteinuria, and the progression rate of renal disease.

Results: Baseline demographics in the two groups were similar. Three hundred and twenty-seven patients receiving losartan reached the primary end point, as compared with 359 on placebo (risk reduction = 16 per cent, p = 0.02). Losartan reduced the incidence of doubling of serum creatinine (risk reduction = 25 per cent, p = 0.006) and end-stage renal disease (risk reduction = 28 per cent, p = 0.002), but had no effect on death. Benefits exceeded that attributable to changes in blood pressure. The composite of cardiovascular morbidity and mortality was similar in the two groups, except hospitalisation for heart failure, which was reduced with losartan (risk reduction = 32 per cent, p = 0.005). Proteinuria declined by 35 per cent with losartan (p < 0.001).

Discussion: Losartan conferred significant renal benefits in type 2 diabetic patients with nephropathy and was generally well tolerated.