Influence of Age on Efficacy and Safety of Spironolactone in Heart Failure

TOPCAT Investigators

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objectives: The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Background: Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics. Methods: TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45% who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories (<65, 65 to 74, and ≥75 years). Results: The mean age was 72 ± 10 years (range 50 to 97 years) with 41% over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95% confidence interval: 1.91 to 3.37; p < 0.001), particularly in older age groups (p interaction = 0.02). Findings in the whole TOPCAT cohort were consistent with results from the Americas region. Conclusions: In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302)

Original languageEnglish (US)
Pages (from-to)1022-1028
Number of pages7
JournalJACC: Heart Failure
Volume7
Issue number12
DOIs
StatePublished - Dec 2019

Fingerprint

Spironolactone
Heart Failure
Safety
Mineralocorticoid Receptor Antagonists
Glomerular Filtration Rate
Placebos
Natriuretic Peptides
Stroke Volume
Hospitalization
Body Mass Index
Therapeutics
Pharmacokinetics
Age Groups
Confidence Intervals

Keywords

  • age
  • heart failure with preserved ejection fraction
  • mineralocorticoid receptor antagonists
  • spironolactone

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Influence of Age on Efficacy and Safety of Spironolactone in Heart Failure. / TOPCAT Investigators.

In: JACC: Heart Failure, Vol. 7, No. 12, 12.2019, p. 1022-1028.

Research output: Contribution to journalArticle

TOPCAT Investigators. / Influence of Age on Efficacy and Safety of Spironolactone in Heart Failure. In: JACC: Heart Failure. 2019 ; Vol. 7, No. 12. pp. 1022-1028.
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abstract = "Objectives: The authors examined efficacy and safety of spironolactone by age in the Americas region (N = 1,767) of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial. Background: Heart failure with preserved ejection fraction disproportionately affects older adults who may exhibit changes in physiology and variable pharmacokinetics. Methods: TOPCAT enrolled patients with heart failure and a left ventricular ejection fraction ≥45{\%} who were age 50 or older with an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 and prior heart failure hospitalization or elevated natriuretic peptide levels. Participants were randomized to spironolactone or placebo with a mean follow-up duration of 3.3 years. We assessed treatment effect and safety by protocol-defined age categories (<65, 65 to 74, and ≥75 years). Results: The mean age was 72 ± 10 years (range 50 to 97 years) with 41{\%} over the age of 75 years. Participants ≥75 years were more commonly women and white and had a lower body mass index and estimated glomerular filtration rate compared with the younger age categories. Spironolactone reduced the primary composite outcome compared with placebo across all age categories (p interaction = 0.42). However, spironolactone was associated with an increased risk of the safety endpoint (hazard ratio: 2.54; 95{\%} confidence interval: 1.91 to 3.37; p < 0.001), particularly in older age groups (p interaction = 0.02). Findings in the whole TOPCAT cohort were consistent with results from the Americas region. Conclusions: In this post hoc, exploratory analysis of the TOPCAT trial data from the Americas region, although there was no effect of age on efficacy, there were considerable effects of age on increased rates of adverse safety outcomes. These results should be weighed when considering spironolactone for older heart failure with preserved ejection fraction patients. (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist [TOPCAT]; NCT00094302)",
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AU - Vardeny, Orly

AU - Claggett, Brian

AU - Vaduganathan, Muthiah

AU - Beldhuis, Iris

AU - Rouleau, Jean

AU - O'Meara, Eileen

AU - Anand, Inder S.

AU - Shah, Sanjiv J.

AU - Sweitzer, Nancy K.

AU - Fang, James C.

AU - Desai, Akshay S.

AU - Lewis, Eldrin F.

AU - Pitt, Bertram

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AU - Solomon, Scott D.

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