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

Bertram Pitt, Roberto Latini, Aldo P. Maggioni, Scott D. Solomon, Beverly A. Smith, Melanie Wright, Margaret F. Prescott, John J V McMurray

Research output: Contribution to journalArticle

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 IIIV 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 β-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 (MRA-) MRA treatment at baseline. Of the 302 randomized patients, 101 were receiving MRA treatment (aliskiren, n 52; placebo, n 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); MRA- group: aliskiren 0.62 (0.45, 0.84), placebo 0.85 (0.63, 1.15), interaction P 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.

Original languageEnglish
Pages (from-to)755-764
Number of pages10
JournalEuropean Journal of Heart Failure
Volume13
Issue number7
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Mineralocorticoid Receptor Antagonists
Heart Failure
Observation
Placebos
Brain Natriuretic Peptide
Therapeutics
Renin
Biomarkers
aliskiren
Safety
Hyperkalemia
Angiotensin Receptor Antagonists
Aldosterone
Angiotensin-Converting Enzyme Inhibitors
Hypotension
Confidence Intervals

Keywords

  • Aliskiren
  • B-type natriuretic peptide
  • Mineralocorticoid receptor antagonist
  • Renin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Neurohumoral effects of aliskiren in patients with symptomatic heart failure receiving a mineralocorticoid receptor antagonist : The Aliskiren Observation of Heart Failure Treatment study. / Pitt, Bertram; Latini, Roberto; Maggioni, Aldo P.; Solomon, Scott D.; Smith, Beverly A.; Wright, Melanie; Prescott, Margaret F.; McMurray, John J V.

In: European Journal of Heart Failure, Vol. 13, No. 7, 07.2011, p. 755-764.

Research output: Contribution to journalArticle

Pitt, Bertram ; Latini, Roberto ; Maggioni, Aldo P. ; Solomon, Scott D. ; Smith, Beverly A. ; Wright, Melanie ; Prescott, Margaret F. ; McMurray, John J V. / Neurohumoral effects of aliskiren in patients with symptomatic heart failure receiving a mineralocorticoid receptor antagonist : The Aliskiren Observation of Heart Failure Treatment study. In: European Journal of Heart Failure. 2011 ; Vol. 13, No. 7. pp. 755-764.
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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 IIIV 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 β-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 (MRA-) MRA treatment at baseline. Of the 302 randomized patients, 101 were receiving MRA treatment (aliskiren, n 52; placebo, n 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); MRA- group: aliskiren 0.62 (0.45, 0.84), placebo 0.85 (0.63, 1.15), interaction P 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.",
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AU - Maggioni, Aldo P.

AU - Solomon, Scott D.

AU - Smith, Beverly A.

AU - Wright, Melanie

AU - Prescott, Margaret F.

AU - McMurray, John J V

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N2 - 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 IIIV 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 β-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 (MRA-) MRA treatment at baseline. Of the 302 randomized patients, 101 were receiving MRA treatment (aliskiren, n 52; placebo, n 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); MRA- group: aliskiren 0.62 (0.45, 0.84), placebo 0.85 (0.63, 1.15), interaction P 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.

AB - 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 IIIV 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 β-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 (MRA-) MRA treatment at baseline. Of the 302 randomized patients, 101 were receiving MRA treatment (aliskiren, n 52; placebo, n 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); MRA- group: aliskiren 0.62 (0.45, 0.84), placebo 0.85 (0.63, 1.15), interaction P 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.

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