Optimal antiproteinuric dose of aliskiren in type 2 diabetes mellitus: a randomised crossover trial.
OBJECTIVE
The optimal antiproteinuric dose of aliskiren is unknown. This study compared the effect of placebo and increasing doses of aliskiren on urinary albumin excretion rate (UAER).


METHODS
The trial was a double-blind crossover design. Twenty-six patients with type 2 diabetes mellitus, hypertension and albuminuria were randomised to 2-month treatments with placebo or aliskiren 150 mg, 300 mg or 600 mg once daily, in random order. Primary endpoint was change in UAER; secondary endpoints included changes in 24-h BP, GFR, biomarkers and components of the renin-angiotensin-aldosterone system.


RESULTS
Placebo geometric mean UAER was 350 mg/day, mean 24-h BP was 137/81 (SD 12/9) mmHg, GFR was 85 (SD 26) ml min(-1) 1.73 m(-2). Aliskiren 150, 300 and 600 mg daily reduced UAER significantly by 36% (95% CI 17-51), 48% (33-60) and 52% (38-63) respectively (p < 0.001) compared with placebo. UAER reduction during the 600 mg dose was not significantly different from the 300 mg dose. Twenty-four-hour systolic BP was reduced by 4.5, 8.0 and 9.2 mmHg versus placebo, significant for 300 and 600 mg (p < or = 0.001). Twenty-four-hour diastolic BP was reduced by 3.0, 4.1 and 4.4 mmHg, significant versus placebo (p = 0.019, p = 0.001 and p < 0.001). GFR was reduced by 3.0, 5.1 and 6.5 ml min(-1) 1.73 m(-2). hsPRA was reduced by 63%, 70%, and 82% (p < 0.001 for all). Adverse events, most frequently dizziness and fatigue, occurred during all doses.


CONCLUSIONS
In patients with type 2 diabetes mellitus, hypertension and albuminuria there is no improved antiproteinuric effect when using 600 mg aliskiren daily compared with the maximal recommended antihypertensive dose of 300 mg.


BACKGROUND
Clinicaltrials.gov NCT00464776


BACKGROUND
Novartis Pharma AG.
Persson
F
F
Steno Diabetes Center, Niels Steensenvej 1, DK-2820 Gentofte, Denmark. frip@steno.dk
Rossing
P
P
Reinhard
H
H
Juhl
T
T
Stehouwer
C D A
CD
Schalkwijk
C
C
Danser
A H J
AH
Boomsma
F
F
Frandsen
E
E
Parving
H-H
HH
D000328:Adult; D000419:Albuminuria / Q000150:complications / Q000188:drug therapy*; D000577:Amides / Q000008:administration & dosage* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005650:Fumarates / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D000092502:Renin Inhibitors
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D000092502:Renin Inhibitors; C446481:aliskiren