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Is there a potential association between spironolactone and the risk of new-onset diabetes in a cohort of older patients with heart failure?

  • Sandra Korol
  • Michel White
  • Eileen O’Meara
  • Jean-Lucien Rouleau
  • Brian White-Guay
  • Marc Dorais
  • Ali Ahmed
  • Simon de DenusEmail author
  • Sylvie PerreaultEmail author
Pharmacoepidemiology and Prescription

Abstract

Purpose

Some evidence suggests that spironolactone may have a deleterious effect on glucose homeostasis. The objective of this study was to assess whether spironolactone use is associated with a higher risk of developing diabetes in a large cohort of patients with heart failure (HF).

Methods

Two Quebec government administrative databases were used to identify a cohort of hospitalized patients discharged between January 1995 and December 2009 with a primary discharge diagnosis of HF and without secondary discharge diagnosis of diabetes. Patients were categorized as new users of spironolactone and non-users. The primary outcome was defined as new-onset diabetes (NOD) during 5 years of follow-up and was ascertained using ICD codes for diabetes or use of hypoglycemic agents.

Results

Among the 2974 patients that were included in the cohort analysis, 769 were given a new prescription of spironolactone. The incidence rate of NOD was similar among spironolactone users (5.0 per 100 person-years) and non-users (4.9 per 100 person-years). There was no significant association between the use of spironolactone and NOD in the crude, unadjusted model (hazard ratio (HR) 1.01; 95% confidence interval (CI) 0.80–1.28; p = 0.9217), and it remained unchanged in the adjusted Cox proportional hazard model (HR = 0.92; 95% CI = 0.72–1.18; p = 0.5227). The results were consistent with those observed in sensitivity analyses of a 1:3 propensity score-matched cohort (HR = 0.97; CI = 0.76–1.25; p = 0.8169).

Conclusion

We found no evidence supporting the claim that use of spironolactone is associated with a higher risk of diabetes among patients hospitalized for HF.

Keywords

Spironolactone Heart failure Diabetes mellitus Mineralocorticoid receptor Aldosterone 

Notes

Funding

Réseau Québécois de Recherche sur Médicament (RQRM).

Compliance with ethical standards

Conflicts of interest

Sandra Korol: Sandra Korol received funding from Fonds de recherche du Québec – Santé (FRQS). Michel White: Dr. White received research grants from Bayer, Jenssen, Novartis, and Pfizer. He was a consultant for Jenssen USA and Arca Biopharma USA, and was a conference speaker for Bayer, Novartis, Pfizer, BMS, Servier, and BI. Simon de Denus: Dr. de Denus has received research grants or been a co-investigator on grants supported by AstraZeneca, Novartis, Roche and Pfizer. He has received speaker fees from Pfizer and consulting fees from Servier and Novartis. All other authors declare that they have no conflicts of interest.

Supplementary material

228_2018_2615_MOESM1_ESM.pdf (229 kb)
ESM 1 (PDF 229 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sandra Korol
    • 1
    • 2
  • Michel White
    • 3
    • 2
  • Eileen O’Meara
    • 3
    • 2
  • Jean-Lucien Rouleau
    • 3
    • 2
  • Brian White-Guay
    • 1
  • Marc Dorais
    • 4
    • 5
  • Ali Ahmed
    • 6
    • 7
  • Simon de Denus
    • 1
    • 2
    Email author
  • Sylvie Perreault
    • 1
    • 4
    Email author
  1. 1.Faculty of PharmacyUniversité de MontréalMontréalCanada
  2. 2.Montreal Heart InstituteMontrealCanada
  3. 3.Faculty of MedicineUniversité de MontréalMontrealCanada
  4. 4.Sanofi Aventis Endowment Research Chair in Optimal Drug UseMontrealCanada
  5. 5.StatSciences Inc.N.-D.-Ile-PerrotCanada
  6. 6.Veterans Affairs Medical CenterWashingtonUSA
  7. 7.George Washington UniversityWashingtonUSA

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