Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes

Franco Cosmi, Li Shen, Michela Magnoli, William T. Abraham, Inder S. Anand, John G. Cleland, Jay N. Cohn, Deborah Cosmi, Giorgia De Berardis, Kenneth Dickstein, Maria Grazia Franzosi, Lars Gullestad, Pardeep S. Jhund, John Kjekshus, Lars Køber, Vito Lepore, Giuseppe Lucisano, Aldo P. Maggioni, Serge Masson, John J.V. McMurray & 9 others Antonio Nicolucci, Vito Petrarolo, Fabio Robusto, Lidia Staszewsky, Luigi Tavazzi, Roberto Teli, Gianni Tognoni, John Wikstrand, Roberto Latini

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine–Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case–control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16–1.38), for HF hospitalization 1.23 (1.13–1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87–2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32–1.53). Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.

Original languageEnglish (US)
Pages (from-to)888-895
Number of pages8
JournalEuropean Journal of Heart Failure
Volume20
Issue number5
DOIs
StatePublished - May 1 2018

Fingerprint

Heart Failure
Insulin
Propensity Score
Hospitalization
Therapeutics
Cause of Death
Diabetes Mellitus
Odds Ratio
Confidence Intervals
Mortality
Random Allocation
Proportional Hazards Models
Hypoglycemia
Hypoglycemic Agents
Type 2 Diabetes Mellitus
Prescriptions
Registries
Cohort Studies
Databases
Glucose

Keywords

  • Diabetes mellitus
  • Heart failure
  • Insulin

PubMed: MeSH publication types

  • Journal Article
  • Multicenter Study
  • Randomized Controlled Trial

Cite this

Cosmi, F., Shen, L., Magnoli, M., Abraham, W. T., Anand, I. S., Cleland, J. G., ... Latini, R. (2018). Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes. European Journal of Heart Failure, 20(5), 888-895. https://doi.org/10.1002/ejhf.1146

Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes. / Cosmi, Franco; Shen, Li; Magnoli, Michela; Abraham, William T.; Anand, Inder S.; Cleland, John G.; Cohn, Jay N.; Cosmi, Deborah; De Berardis, Giorgia; Dickstein, Kenneth; Franzosi, Maria Grazia; Gullestad, Lars; Jhund, Pardeep S.; Kjekshus, John; Køber, Lars; Lepore, Vito; Lucisano, Giuseppe; Maggioni, Aldo P.; Masson, Serge; McMurray, John J.V.; Nicolucci, Antonio; Petrarolo, Vito; Robusto, Fabio; Staszewsky, Lidia; Tavazzi, Luigi; Teli, Roberto; Tognoni, Gianni; Wikstrand, John; Latini, Roberto.

In: European Journal of Heart Failure, Vol. 20, No. 5, 01.05.2018, p. 888-895.

Research output: Contribution to journalArticle

Cosmi, F, Shen, L, Magnoli, M, Abraham, WT, Anand, IS, Cleland, JG, Cohn, JN, Cosmi, D, De Berardis, G, Dickstein, K, Franzosi, MG, Gullestad, L, Jhund, PS, Kjekshus, J, Køber, L, Lepore, V, Lucisano, G, Maggioni, AP, Masson, S, McMurray, JJV, Nicolucci, A, Petrarolo, V, Robusto, F, Staszewsky, L, Tavazzi, L, Teli, R, Tognoni, G, Wikstrand, J & Latini, R 2018, 'Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes', European Journal of Heart Failure, vol. 20, no. 5, pp. 888-895. https://doi.org/10.1002/ejhf.1146
Cosmi, Franco ; Shen, Li ; Magnoli, Michela ; Abraham, William T. ; Anand, Inder S. ; Cleland, John G. ; Cohn, Jay N. ; Cosmi, Deborah ; De Berardis, Giorgia ; Dickstein, Kenneth ; Franzosi, Maria Grazia ; Gullestad, Lars ; Jhund, Pardeep S. ; Kjekshus, John ; Køber, Lars ; Lepore, Vito ; Lucisano, Giuseppe ; Maggioni, Aldo P. ; Masson, Serge ; McMurray, John J.V. ; Nicolucci, Antonio ; Petrarolo, Vito ; Robusto, Fabio ; Staszewsky, Lidia ; Tavazzi, Luigi ; Teli, Roberto ; Tognoni, Gianni ; Wikstrand, John ; Latini, Roberto. / Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes. In: European Journal of Heart Failure. 2018 ; Vol. 20, No. 5. pp. 888-895.
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abstract = "Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine–Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case–control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5{\%} to 29.5{\%} across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4{\%} to 34.5{\%} of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16–1.38), for HF hospitalization 1.23 (1.13–1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95{\%} confidence interval (CI) 1.87–2.19] and rehospitalization for HF (OR 1.42, 95{\%} CI 1.32–1.53). Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.",
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T1 - Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes

AU - Cosmi, Franco

AU - Shen, Li

AU - Magnoli, Michela

AU - Abraham, William T.

AU - Anand, Inder S.

AU - Cleland, John G.

AU - Cohn, Jay N.

AU - Cosmi, Deborah

AU - De Berardis, Giorgia

AU - Dickstein, Kenneth

AU - Franzosi, Maria Grazia

AU - Gullestad, Lars

AU - Jhund, Pardeep S.

AU - Kjekshus, John

AU - Køber, Lars

AU - Lepore, Vito

AU - Lucisano, Giuseppe

AU - Maggioni, Aldo P.

AU - Masson, Serge

AU - McMurray, John J.V.

AU - Nicolucci, Antonio

AU - Petrarolo, Vito

AU - Robusto, Fabio

AU - Staszewsky, Lidia

AU - Tavazzi, Luigi

AU - Teli, Roberto

AU - Tognoni, Gianni

AU - Wikstrand, John

AU - Latini, Roberto

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine–Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case–control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16–1.38), for HF hospitalization 1.23 (1.13–1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87–2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32–1.53). Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.

AB - Aims: Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results: We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine–Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case–control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16–1.38), for HF hospitalization 1.23 (1.13–1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87–2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32–1.53). Conclusions: Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.

KW - Diabetes mellitus

KW - Heart failure

KW - Insulin

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