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.
RCT Entities:
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.
Authors: Nicolas F Schroten; Carlo A J M Gaillard; Dirk J van Veldhuisen; Mariusz K Szymanski; Hans L Hillege; Rudolf A de Boer Journal: Heart Fail Rev Date: 2012-03 Impact factor: 4.214
Authors: Ryan D Sullivan; Radhika M Mehta; Ranjana Tripathi; Inna P Gladysheva; Guy L Reed Journal: Int J Mol Sci Date: 2019-08-09 Impact factor: 5.923