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. Methods and results 27 patients with NYHA class II or III CHF and an ejection fraction ≤0.35, were randomised to placebo, the ACE inhibitor ramipril or the RI aliskiren for 1week after a 5–7day washout period following ACE inhibitor withdrawal. Thereafter, patients were treated with either ramipril (target dose 10mg qd) or aliskiren (target dose 300mg qd) for a further 5weeks. 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 (6weeks), 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.