Renal and retinal effects of enalapril and losartan in type 1 diabetes. Export

@article{citeulike:5046075, abstract = {BACKGROUND: Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether their progression is slowed by early administration of drugs that block the renin-angiotensin system. METHODS: We conducted a multicenter, controlled trial involving 285 normotensive patients with type 1 diabetes and normoalbuminuria and who were randomly assigned to receive losartan (100 mg daily), enalapril (20 mg daily), or placebo and followed for 5 years. The primary end point was a change in the fraction of glomerular volume occupied by mesangium in kidney-biopsy specimens. The retinopathy end point was a progression on a retinopathy severity scale of two steps or more. Intention-to-treat analysis was performed with the use of linear regression and logistic-regression models. RESULTS: A total of 90\% and 82\% of patients had complete renal-biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over the 5-year period did not differ significantly between the placebo group (0.016 units) and the enalapril group (0.005, P=0.38) or the losartan group (0.026, P=0.26), nor were there significant treatment benefits for other biopsy-assessed renal structural variables. The 5-year cumulative incidence of microalbuminuria was 6\% in the placebo group; the incidence was higher with losartan (17\%, P=0.01 by the log-rank test) but not with enalapril (4\%, P=0.96 by the log-rank test). As compared with placebo, the odds of retinopathy progression by two steps or more was reduced by 65\% with enalapril (odds ratio, 0.35; 95\% confidence interval [CI], 0.14 to 0.85) and by 70\% with losartan (odds ratio, 0.30; 95\% CI, 0.12 to 0.73), independently of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 patients receiving enalapril, 6 receiving losartan, and 4 receiving placebo. CONCLUSIONS: Early blockade of the renin-angiotensin system in patients with type 1 diabetes did not slow nephropathy progression but slowed the progression of retinopathy. (ClinicalTrials.gov number, NCT00143949.)}, author = {Mauer, Michael and Zinman, Bernard and Gardiner, Robert and Suissa, Samy and Sinaiko, Alan and Strand, Trudy and Drummond, Keith and Donnelly, Sandra and Goodyer, Paul and Gubler, Marie Claire C. and Klein, Ronald}, citeulike-article-id = {5046075}, citeulike-linkout-0 = {http://dx.doi.org/10.1056/NEJMoa0808400}, citeulike-linkout-1 = {http://content.nejm.org/cgi/content/abstract/361/1/40}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19571282}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19571282}, day = {2}, doi = {10.1056/NEJMoa0808400}, issn = {1533-4406}, journal = {The New England journal of medicine}, keywords = {dm, htn}, month = {July}, number = {1}, pages = {40--51}, posted-at = {2009-07-03 13:57:43}, priority = {2}, title = {Renal and retinal effects of enalapril and losartan in type 1 diabetes.}, url = {http://dx.doi.org/10.1056/NEJMoa0808400}, volume = {361}, year = {2009} }

TY - JOUR ID - citeulike:5046075 L3 - citeulike-article-id:5046075 N2 - BACKGROUND: Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether their progression is slowed by early administration of drugs that block the renin-angiotensin system. METHODS: We conducted a multicenter, controlled trial involving 285 normotensive patients with type 1 diabetes and normoalbuminuria and who were randomly assigned to receive losartan (100 mg daily), enalapril (20 mg daily), or placebo and followed for 5 years. The primary end point was a change in the fraction of glomerular volume occupied by mesangium in kidney-biopsy specimens. The retinopathy end point was a progression on a retinopathy severity scale of two steps or more. Intention-to-treat analysis was performed with the use of linear regression and logistic-regression models. RESULTS: A total of 90% and 82% of patients had complete renal-biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over the 5-year period did not differ significantly between the placebo group (0.016 units) and the enalapril group (0.005, P=0.38) or the losartan group (0.026, P=0.26), nor were there significant treatment benefits for other biopsy-assessed renal structural variables. The 5-year cumulative incidence of microalbuminuria was 6% in the placebo group; the incidence was higher with losartan (17%, P=0.01 by the log-rank test) but not with enalapril (4%, P=0.96 by the log-rank test). As compared with placebo, the odds of retinopathy progression by two steps or more was reduced by 65% with enalapril (odds ratio, 0.35; 95% confidence interval [CI], 0.14 to 0.85) and by 70% with losartan (odds ratio, 0.30; 95% CI, 0.12 to 0.73), independently of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 patients receiving enalapril, 6 receiving losartan, and 4 receiving placebo. CONCLUSIONS: Early blockade of the renin-angiotensin system in patients with type 1 diabetes did not slow nephropathy progression but slowed the progression of retinopathy. (ClinicalTrials.gov number, NCT00143949.) IS - 1 JF - The New England journal of medicine SN - 1533-4406 EP - 51 TI - Renal and retinal effects of enalapril and losartan in type 1 diabetes. VL - 361 SP - 40 KW - dm KW - htn AU - Mauer, Michael AU - Zinman, Bernard AU - Gardiner, Robert AU - Suissa, Samy AU - Sinaiko, Alan AU - Strand, Trudy AU - Drummond, Keith AU - Donnelly, Sandra AU - Goodyer, Paul AU - Gubler, Marie Claire AU - Klein, Ronald PY - 2009/07/02/ UR - http://dx.doi.org/10.1056/NEJMoa0808400 ER -