Optimal antiproteinuric dose of aliskiren in type 2 diabetes mellitus: a
randomised crossover trial.
Author(s): Persson F, Rossing P, Reinhard H, Juhl T, Stehouwer CD, Schalkwijk C, Danser AH,
Boomsma F, Frandsen E, Parving HH.
Affiliation(s): Steno Diabetes Center, Niels Steensenvej 1, DK-2820 Gentofte, Denmark.
frip@steno.dk
Publication date & source: 2010, Diabetologia. , 53(8):1576-80
AIM: 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.
TRIAL REGISTRATION: Clinicaltrials.gov NCT00464776
FUNDING: Novartis Pharma AG.
|