Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan.
BACKGROUND
By blocking the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step, renin inhibition may provide improved RAAS suppression. We investigated the blood pressure (BP)-lowering effects of the oral direct renin inhibitor aliskiren, alone or in combination with the angiotensin receptor blocker valsartan.


METHODS
In this multicenter, randomized, placebo-controlled, 8-week trial, 1123 patients with mild-to-moderate hypertension underwent a 3 to 4 week single-blind placebo run-in and were then randomized in a modified factorial study design to receive once-daily, double-blind oral treatment with placebo, aliskiren monotherapy (75, 150, or 300 mg), valsartan monotherapy (80, 160, or 320 mg), aliskiren and valsartan in combination, or valsartan/hydrochlorothiazide (160/12.5 mg). The primary efficacy variable was the change from baseline in mean sitting diastolic BP (DBP) at endpoint.


RESULTS
Once-daily oral treatment with aliskiren 300 mg significantly (P < .0001) lowered mean sitting DBP and systolic BP (SBP) compared with placebo; aliskiren monotherapy demonstrated a safety and tolerability profile comparable to placebo. Changes in DBP and SBP were fitted to a first-order dose-response surface (lack-of-fit test, P = .65), which showed that aliskiren and valsartan alone and in combination produced dose-related reductions in DBP and SBP. Coadministration of aliskiren and valsartan produced a greater antihypertensive effect than either drug alone, comparable in magnitude to the effect of valsartan/hydrochlorothiazide, with similar tolerability to the component monotherapies and to placebo.


CONCLUSIONS
Aliskiren monotherapy provides antihypertensive efficacy and placebo-like tolerability in patients with hypertension. Aliskiren and valsartan in combination may provide additive BP-lowering effects with maintained tolerability.
Pool
James L
JL
Center for Experimental Therapeutics, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA. jpool@bcm.tmc.edu
Schmieder
Roland E
RE
Azizi
Michel
M
Aldigier
Jean-Claude
JC
Januszewicz
Andrzej
A
Zidek
Walter
W
Chiang
Yanntong
Y
Satlin
Andrew
A
D000328:Adult; D000368:Aged; D000577:Amides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005650:Fumarates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D000068756:Valsartan
D000577:Amides; D000959:Antihypertensive Agents; D005650:Fumarates; D013777:Tetrazoles; D006852:Hydrochlorothiazide; C446481:aliskiren; D000068756:Valsartan; D014633:Valine