Additive effect of ACE inhibition and angiotensin II receptor blockade in type I diabetic patients with diabetic nephropathy.
Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in diabetic patients. This study tested whether dual blockade of the renin-angiotensin system (RAS) with both an angiotensin-converting enzyme (ACE) inhibitor (ACE-I) and an Angiotensin-II receptor blocker (ARB) is superior to either drug alone in type I diabetic patients with diabetic nephropathy (DN). A randomized double-blind crossover trial was performed with 8-wk treatment with placebo, 20 mg of benazepril once daily, 80 mg of valsartan once daily, and the combination of 20 mg of benazepril and 80 mg of valsartan. Twenty type I diabetic patients with DN were included. At the end of each treatment period, albuminuria, 24-h BP, and GFR were measured. Eighteen patients completed the study. Placebo values were: albuminuria [mean (95% CI)], 701 (490 to 1002) mg/24 h; BP [mean (SEM)], 144 (4)/79 (2) mmHg, and GFR [mean (SEM)], 82 (7) ml/min per 1.73 m(2). Treatment with benazepril, valsartan, or dual blockade significantly reduced albuminuria and BP compared with placebo. Benazepril and valsartan were equally effective. Dual blockade induced an additional reduction in albuminuria of 43 % (29 to 54 %) compared with any type of monotherapy, and a reduction in systolic BP of 6 (0 to 13) mmHg and 7 (1 to 14) mmHg (versus benazepril and valsartan, respectively) and a reduction of 7 (4 to 10) mmHg diastolic compared with both monotherapies. GFR was reversibly reduced on dual blockade compared with monotherapy and placebo. All treatments were safe and well tolerated. In conclusion, dual blockade of the RAS may offer additional renal and cardiovascular protection in type I diabetic patients with DN.
Jacobsen
Peter
P
Steno Diabetes Center, Gentofte, Denmark and Faculty of Health Science, University of Aarhus, Denmark. pkjacobsen@dadlnet.dk
Andersen
Steen
S
Jensen
Berit R
BR
Parving
Hans-Henrik
HH
D000328:Adult; D000419:Albuminuria; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001552:Benzazepines / Q000627:therapeutic use*; D001794:Blood Pressure; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004357:Drug Synergism; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000068756:Valsartan
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001552:Benzazepines; D013777:Tetrazoles; D000068756:Valsartan; D014633:Valine; C044946:benazepril