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


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.
Seed
Alison
A
Department of Cardiology, Western Infirmary, Glasgow, United Kingdom.
Gardner
Roy
R
McMurray
John
J
Hillier
Chris
C
Murdoch
David
D
MacFadyen
Robert
R
Bobillier
Alain
A
Mann
Jessica
J
McDonagh
Theresa
T
D000368:Aged; D000450:Aldosterone / Q000097:blood; D000577:Amides / Q000627:therapeutic use*; D000704:Analysis of Variance; D000804:Angiotensin II / Q000097:blood; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D002908:Chronic Disease; D005260:Female; D005650:Fumarates / Q000627:therapeutic use*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020097:Natriuretic Peptide, Brain / Q000097:blood; D017257:Ramipril / Q000627:therapeutic use; D012083:Renin / Q000097:blood; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D000092502:Renin Inhibitors
D000450:Aldosterone; D000577:Amides; D000804:Angiotensin II; D000806:Angiotensin-Converting Enzyme Inhibitors; D005650:Fumarates; D020097:Natriuretic Peptide, Brain; D017257:Ramipril; D012083:Renin; D000092502:Renin Inhibitors; C446481:aliskiren