Neurohumoral effects of the new orally active renin inhibitor, aliskiren, in chronic heart failure

Eur J Heart Fail. 2007 Nov;9(11):1120-7. doi: 10.1016/j.ejheart.2007.09.002. Epub 2007 Oct 18.

Abstract

Background: Suppression of the renin-angiotensin-aldosterone system (RAAS) is therapeutically valuable in chronic heart failure (CHF). RAAS inhibition can be achieved in a number of ways though an orally active renin inhibitor (RI) has never been studied before. We describe the neurohumoral effects of an RI.

Methods and results: 27 patients with NYHA class II or III CHF and an ejection fraction <or=0.35, were randomised to placebo, the ACE inhibitor ramipril or the RI aliskiren for 1 week after a 5-7 day washout period following ACE inhibitor withdrawal. Thereafter, patients were treated with either ramipril (target dose 10 mg qd) or aliskiren (target dose 300 mg qd) for a further 5 weeks. Plasma renin activity (PRA), angiotensin II, aldosterone and B-type natriuretic peptide (BNP) were measured at baseline (pre-randomisation), after one week and at two week intervals thereafter. The mean changes (%) at the end of the study (6 weeks), compared with baseline, were: PRA 164.9 (SD 149)% ramipril, -60.1 (24)% aliskiren (between groups p value<0.0001); angiotensin II 39.7 (138)% ramipril, -51.4 (40)% aliskiren (p<0.05); aldosterone -0.94 (67)% ramipril, 4.74 (60)% aliskiren (p=n.s.); BNP-7.51 (38)% ramipril, -1.79 (43)% aliskiren (p=n.s.).

Conclusions: Aliskiren appeared to suppress the RAAS as effectively as ramipril in the short term. RIs may offer an alternative therapeutic approach to the blockade of the RAAS.

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aldosterone / blood
  • Amides / therapeutic use*
  • Analysis of Variance
  • Angiotensin II / blood
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Chronic Disease
  • Female
  • Fumarates / therapeutic use*
  • Heart Failure / blood
  • Heart Failure / drug therapy*
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Ramipril / therapeutic use
  • Renin / antagonists & inhibitors*
  • Renin / blood
  • Statistics, Nonparametric
  • Treatment Outcome

Substances

  • Amides
  • Angiotensin-Converting Enzyme Inhibitors
  • Fumarates
  • Angiotensin II
  • Natriuretic Peptide, Brain
  • Aldosterone
  • aliskiren
  • Renin
  • Ramipril