November 1, 2007
View Full PaperNeurohumoral Effects of the New Orally Active Renin Inhibitor, Aliskiren, in Chronic Heart Failure
Key Result
Aliskiren significantly reduced plasma renin activity by 60.1% compared to a 164.9% increase with ramipril at 6 weeks (p<0.0001), demonstrating effective short-term RAAS suppression in CHF.
Study Design
Type
RCT (n=27)
Structured PICO
Does aliskiren reduce neurohumoral activation compared to ramipril in patients with chronic heart failure?
P
Population
27 patients with chronic heart failure (NYHA class II or III) and an ejection fraction ≤0.35
I
Intervention
Aliskiren (target dose 300 mg qd) for 6 weeks
C
Comparator
Ramipril (target dose 10 mg qd) for 6 weeks
O
Outcome
Mean changes (%) in plasma renin activity (PRA), angiotensin II, aldosterone, and B-type natriuretic peptide (BNP) at 6 weeks compared with baselinesurrogate
Aliskiren provides effective short-term suppression of the renin-angiotensin-aldosterone system comparable to ramipril in patients with chronic heart failure.
Main Result
Absolute Event Rate: -60.1% vs 164.9%
p-value: p=<0.0001
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.