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

Author(s): Seed A, Gardner R, McMurray J, Hillier C, Murdoch D, MacFadyen R, Bobillier A, Mann J, McDonagh T

Affiliation(s): Department of Cardiology, Western Infirmary, Glasgow, United Kingdom.

Publication date & source: 2007-11, Eur J Heart Fail., 9(11):1120-7. Epub 2007 Oct 18.

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.

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