Neurohumoral effects of aliskiren in patients with symptomatic heart failure receiving a mineralocorticoid receptor antagonist: the Aliskiren Observation of Heart Failure Treatment study

Abstract

AimsWe evaluated the influence of concomitant mineralocorticoid receptor antagonists (MRAs) on the safety and neurohumoral effects of a direct renin inhibitor in the ALiskiren Observation of Heart Failure Treatment (ALOFT) study. Methods and resultsPatients with stable New York Heart Association class II -IV heart failure (HF), plasma B-type natriuretic peptide (BNP) concentration .100 pg/mL, and treated with an angiotensin-converting enzyme inhibitor (or angiotensin receptor blocker) and b-blocker were randomized to once-daily, double-blind treatment with aliskiren 150 mg or placebo, added to optimal HF therapy, for 12 weeks. Safety, tolerability, and effects of aliskiren on neurohumoral biomarkers were assessed in patients who received (MRA+) and did not receive (MRA2) MRA treatment at baseline. Of the 302 randomized patients, 101 were receiving MRA treatment (aliskiren, n ¼ 52; placebo, n ¼ 49). Mineralocorticoid receptor antagonist status did not affect the ability of aliskiren 150 mg, added to standard HF therapy, to lower BNP, N-terminal proBNP, plasma renin activity, and urinary aldosterone. For example, the end-of-study to baseline ratio of geometric mean for BNP was: MRA+ group: aliskiren 0.68 [95% confidence interval (CI) 0.47, 0.98], placebo 0.85 (0.58, 1.24); MRA2 group: aliskiren 0.62 (0.45, 0.84), placebo 0.85 (0.63, 1.15), interaction P ¼ 0.720. The incidence of pre-specified adverse events (renal dysfunction, symptomatic hypotension, and hyperkalaemia) was low, and there were no significant differences between aliskiren and placebo in either MRA subgroup. ConclusionAliskiren 150 mg added to standard HF therapy was well tolerated over 12 weeks and provided beneficial changes in neurohumoral biomarkers regardless of concomitant MRA treatment.--

Dual renin-angiotensin system inhibition for prevention of renal and cardiovascular events: do the latest trials challenge existing evidence?

“…These beneficial changes in neurohumoral biomarkers were observed regardless of concomitant mineralocorticoid treatment received by 33% of patients. The incidence of pre-specified adverse events (AEs) of renal dysfunction, symptomatic hypotension and hyperkalaemia was low, and not significantly different between aliskiren and placebo, irrespective of whether or not patients were receiving mineralocorticoid treatment [75]. …”

Heart failure highlights in 2012–2013

“…Aliskiren, a direct renin inhibitor, has been shown to have favourable neurohormonal effects in chronic HF. 68,69,70 In the ASTRONAUT study, aliskiren had no effect on mortality and HF rehospitalizations in stable acute HF patients, despite a significant reduction in NT-proBNP levels. 5 The ongoing ATMOSPHERE study may provide further insights regarding the incremental value of aliskiren in the treatment of chronic HF (NCT00853658).…”

“…Currently, omecamtiv is being investigated in chronic HF in the COSMIC‐HF trial (NCT01786512). Aliskiren, a direct renin inhibitor, has been shown to have favourable neurohormonal effects in chronic HF , . In the ASTRONAUT study, aliskiren had no effect on mortality and HF rehospitalizations in stable acute HF patients, despite a significant reduction in NT‐proBNP levels .…”

New medical therapies for heart failure

“…108 These beneficial effects were seen irrespective of concomitant treatment with mineralocorticoid-receptor antagonists (MRAs) or ACE inhibtors. 109,110 In the phase III ALTITUDE trial, 111 8,561 patients with type 2 diabetes mellitus in addition to chronic kidney disease, cardiovascular disease, or both, were randomly assigned to receive aliskiren or placebo, along with an ACE inhibitor or ARB. The trial was stopped prematurely because of safety concerns and lack of effect of treatment.…”