TY - JOUR

T1 - Renal effects of aliskiren compared with and in combination with irbesartan in patients with type 2 diabetes, hypertension, and albuminuria

AU - Persson, Frederik

AU - Rossing, Peter

AU - Reinhard, Henrik

AU - Juhl, Tina

AU - Stehouwer, Coen D A

AU - Schalkwijk, Casper

AU - Danser, A H Jan

AU - Boomsma, Frans

AU - Frandsen, Erik

AU - Parving, Hans-Henrik

N1 - Keywords: Aged; Albuminuria; Amides; Antihypertensive Agents; Biphenyl Compounds; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Fumarates; Humans; Hypertension; Kidney; Male; Middle Aged; Tetrazoles; Treatment Outcome

PY - 2009

Y1 - 2009

N2 - 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 m(2). 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 m(2) by aliskiren, 8.0 (3.6-12.3) ml/min per 1.73 m(2) by irbesartan, and 11.7 (7.4-15.9) ml/min per 1.73 m(2) by the combination. CONCLUSIONS: The combination of aliskiren and irbesartan is more antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy.

AB - 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 m(2). 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 m(2) by aliskiren, 8.0 (3.6-12.3) ml/min per 1.73 m(2) by irbesartan, and 11.7 (7.4-15.9) ml/min per 1.73 m(2) by the combination. CONCLUSIONS: The combination of aliskiren and irbesartan is more antiproteinuric in type 2 diabetic patients with albuminuria than monotherapy.

U2 - 10.2337/dc09-0168

DO - 10.2337/dc09-0168

M3 - Journal article

C2 - 19587362

VL - 32

SP - 1873

EP - 1879

JO - Diabetes Care

JF - Diabetes Care

SN - 0149-5992

IS - 10

ER -