Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan

Am J Hypertens. 2007 Jan;20(1):11-20. doi: 10.1016/j.amjhyper.2006.06.003.


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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Amides / administration & dosage
  • Amides / adverse effects
  • Amides / therapeutic use*
  • Antihypertensive Agents / administration & dosage
  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / therapeutic use*
  • Blood Pressure / drug effects
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Fumarates / administration & dosage
  • Fumarates / adverse effects
  • Fumarates / therapeutic use*
  • Humans
  • Hydrochlorothiazide / therapeutic use*
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Middle Aged
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use*
  • Valine / analogs & derivatives*
  • Valine / pharmacology
  • Valine / therapeutic use
  • Valsartan


  • Amides
  • Antihypertensive Agents
  • Fumarates
  • Tetrazoles
  • Hydrochlorothiazide
  • aliskiren
  • Valsartan
  • Valine