Journal Article

Renal Effects of Aliskiren Compared With and in Combination With Irbesartan in Patients With Type 2 Diabetes, Hypertension, and Albuminuria

Stehouwer, Coen D.A, Parving, Hans-Henrik, Reinhard, Henrik, Juhl, Tina, Danser, A.H. Jan, Frandsen, Erik, Persson, Frederik, Rossing, Peter, Boomsma, Frans, Schalkwijk, Casper

2009

Overview

OBJECTIVE: We investigated whether the antiproteinuric effect of the direct renin inhibitor aliskiren is comparable to that of irbesartan and the effect of the combination. RESEARCH DESIGN AND METHODS: This was a double-blind, randomized, crossover trial. After a 1-month washout period, 26 patients with type 2 diabetes, hypertension, and albuminuria (>100 mg/day) were randomly assigned to four 2-month treatment periods in random order with placebo, 300 mg aliskiren once daily, 300 mg irbesartan once daily, or the combination using identical doses. Patients received furosemide in a stable dose throughout the study. The primary end point was a change in albuminuria. Secondary measures included change in 24-h blood pressure and glomerular filtration rate (GFR). RESULTS: Placebo geometric mean albuminuria was 258 mg/day (range 84-2,361), mean ± SD 24-h blood pressure was 140/73 ± 15/8 mmHg, and GFR was 89 ± 27 ml/min per 1.73 m². Aliskiren treatment reduced albuminuria by 48% (95% CI 27-62) compared with placebo (P < 0.001), not significantly different from the 58% (42-79) reduction with irbesartan treatment (P < 0.001 vs. placebo). Combination treatment reduced albuminuria by 71% (59-79), more than either monotherapy (P < 0.001 and P = 0.028). Fractional clearances of albumin were significantly reduced (46, 56, and 67% reduction vs. placebo). Twenty-four-hour blood pressure was reduced 3/4 mmHg by aliskiren (NS/P = 0.009), 12/5 mmHg by irbesartan (P < 0.001/P = 0.002), and 10/6 mmHg by the combination (P = 0.001/P < 0.001). GFR was significantly reduced 4.6 (95% CI 0.3-8.8) ml/min per 1.73 m² by aliskiren, 8.0 (3.6-12.3) ml/min per 1.73 m² by irbesartan, and 11.7 (7.4-15.9) ml/min per 1.73 m² by the combination. CONCLUSIONS: The combination of aliskiren and irbesartan is more antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy.

• Publisher: American Diabetes Association
• Subject: Aged / albumins / Albuminuria / Albuminuria - drug therapy / Amides / Amides - pharmacology / Amides - therapeutic use / Analysis / Antihypertensive Agents / Antihypertensive Agents - pharmacology / Antihypertensive Agents - therapeutic use / Biomarkers / Biphenyl Compounds / Biphenyl Compounds - pharmacology / Biphenyl Compounds - therapeutic use / blood pressure / Cardiovascular disease / Clinical medicine / cross-over studies / Diabetes Mellitus, Type 2 / Diabetes Mellitus, Type 2 - drug therapy / Diabetics / Double-Blind Method / drug effects / Drug therapy / Drug Therapy, Combination / Female / Fumarates / Fumarates - pharmacology / Fumarates - therapeutic use / furosemide / glomerular filtration rate / Heart failure / Humans / Hypertension / Hypertension - drug therapy / Irbesartan / Kidney / Kidney - drug effects / Male / Medical research / Medicine, Experimental / Middle Aged / Mortality / noninsulin-dependent diabetes mellitus / Original Research / patients / Peptide hormones / pharmacology / Plasma / renin / Sample size / Studies / Tetrazoles / Tetrazoles - pharmacology / Tetrazoles - therapeutic use / therapeutic use / Treatment Outcome / Type 2 diabetes