Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus

Anders Holt; Jarl E Strange; Nina Nouhravesh; Sebastian Kinnberg Nielsen; Mariam Elmegaard Malik; Anne-Marie Schjerning; Lars Køber; Christian Torp-Pedersen; Gunnar H Gislason; Patricia McGettigan; Morten Schou; Morten Lamberts

doi:10.1016/j.jacc.2023.02.027

Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus

Anders Holt^*
, Jarl E Strange
, Nina Nouhravesh
, Sebastian Kinnberg Nielsen
, Mariam Elmegaard Malik
, Anne-Marie Schjerning
, Lars Køber
, Christian Torp-Pedersen
, Gunnar H Gislason
, Patricia McGettigan
, Morten Schou
, Morten Lamberts

^*Corresponding author for this work

Cardiology

Research output: Contribution to journal › Article › Research › peer-review

Abstract

BACKGROUND: Fluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy.

OBJECTIVES: The authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM.

METHODS: Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis. Associations between NSAIDs and first-time HF hospitalization were investigated using a case-crossover design with 28-day exposure windows, and ORs with 95% CIs were reported.

RESULTS: Included were 331,189 patients with T2DM: 44.2% female, median age of 62 years (IQR: 52-71 years); 23,308 patients were hospitalized with HF during follow-up, and 16% of patients claimed at least 1 NSAID prescription within 1 year. Short-term use of NSAIDs was associated with increased risk of HF hospitalization (OR: 1.43; 95% CI: 1.27-1.63), most notably in subgroups with age ≥80 years (OR: 1.78; 95% CI: 1.39-2.28), elevated hemoglobin (Hb) A1c levels treated with 0 to 1 antidiabetic drug (OR: 1.68; 95% CI: 1.00-2.88), and without previous use of NSAIDs (OR: 2.71; 95% CI: 1.78-4.23).

CONCLUSIONS: NSAIDs were widely used and were associated with an increased risk of first-time HF hospitalization in patients with T2DM. Patients with advanced age, elevated HbA1c levels, and new users of NSAID seemed more susceptible. These findings could guide physicians prescribing NSAIDs.

Original language	English
Pages (from-to)	1459-1470
Number of pages	12
Journal	Journal of the American College of Cardiology
Volume	81
Issue number	15
DOIs	https://doi.org/10.1016/j.jacc.2023.02.027
Publication status	Published - 18 Apr 2023

Funding

Dr Holt-and this study-have been funded by external, independent grants from Ib Mogens Kristiansens Almene Fond (J. nr. 30206-383),Helsefonden (20-B-0035), Snedkermester Sophus Jacobsen og hustru Astrid Jacobsen Fond (J 167/1), Marie og M.B. Richters Fond (J. nr.2020-0379), and Dagmar Marshalls Fond. None of the funders had any influence on the conduction of this study. Dr Torp-Pedersen has received research grants from Novo and Bayer. Dr Kober has received speaker fees from Novo, AstraZeneca, Novartis, and Boehringer Ingelheim. Dr Lamberts has received research grants from Karen Elise Jensen Fonden, Danish Heart Foundation, Bayer, and BMS; has received speaker fees from BMS/Pfizer, Bayer, AstraZeneca, MSD, and Merck; and has held advisory board positions with BMS/Pfizer, Bayer, and Mundipharma. Dr Schou has received speaker fees from Novartis, Bohringer Ingelheim, Bayer, Novo, and AstraZeneca. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Funders	Funder number
IMK Foundation	30206-383
Helsefondon	20-B-0035
Snedkermester Sophus Jacobsen og hustru Astrid Jacobsens Fond	J 167/1
Richter Fonden	2020-0379
Dagmar Marshall Fund
Novo Nordisk Foundation
Bayer
Karen Elise Jensen Foundation
The Danish Heart Foundation
Bristol-Myers Squibb

Keywords

Humans
Female
Middle Aged
Aged
Aged, 80 and over
Male
Diabetes Mellitus, Type 2/complications
Anti-Inflammatory Agents, Non-Steroidal/adverse effects
Heart Failure/drug therapy
Vascular Diseases/complications
KEY WORDS heart failure
Type 2 diabetes mellitus
Pharmacoepidemiology
Nonsteroidal anti-inflammatory drug

Access to Document

10.1016/j.jacc.2023.02.027

Cite this

Holt, A., Strange, J. E., Nouhravesh, N., Nielsen, S. K., Malik, M. E., Schjerning, A.-M., Køber, L., Torp-Pedersen, C., Gislason, G. H., McGettigan, P., Schou, M., & Lamberts, M. (2023). Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus. Journal of the American College of Cardiology, 81(15), 1459-1470. https://doi.org/10.1016/j.jacc.2023.02.027

@article{b0eeffb9a1da4b8cb56d9a295773c838,

title = "Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus",

abstract = "BACKGROUND: Fluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy.OBJECTIVES: The authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM.METHODS: Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis. Associations between NSAIDs and first-time HF hospitalization were investigated using a case-crossover design with 28-day exposure windows, and ORs with 95\% CIs were reported.RESULTS: Included were 331,189 patients with T2DM: 44.2\% female, median age of 62 years (IQR: 52-71 years); 23,308 patients were hospitalized with HF during follow-up, and 16\% of patients claimed at least 1 NSAID prescription within 1 year. Short-term use of NSAIDs was associated with increased risk of HF hospitalization (OR: 1.43; 95\% CI: 1.27-1.63), most notably in subgroups with age ≥80 years (OR: 1.78; 95\% CI: 1.39-2.28), elevated hemoglobin (Hb) A1c levels treated with 0 to 1 antidiabetic drug (OR: 1.68; 95\% CI: 1.00-2.88), and without previous use of NSAIDs (OR: 2.71; 95\% CI: 1.78-4.23).CONCLUSIONS: NSAIDs were widely used and were associated with an increased risk of first-time HF hospitalization in patients with T2DM. Patients with advanced age, elevated HbA1c levels, and new users of NSAID seemed more susceptible. These findings could guide physicians prescribing NSAIDs.",

keywords = "Humans, Female, Middle Aged, Aged, Aged, 80 and over, Male, Diabetes Mellitus, Type 2/complications, Anti-Inflammatory Agents, Non-Steroidal/adverse effects, Heart Failure/drug therapy, Vascular Diseases/complications, KEY WORDS heart failure, Type 2 diabetes mellitus, Pharmacoepidemiology, Nonsteroidal anti-inflammatory drug",

author = "Anders Holt and Strange, \{Jarl E\} and Nina Nouhravesh and Nielsen, \{Sebastian Kinnberg\} and Malik, \{Mariam Elmegaard\} and Anne-Marie Schjerning and Lars K{\o}ber and Christian Torp-Pedersen and Gislason, \{Gunnar H\} and Patricia McGettigan and Morten Schou and Morten Lamberts",

year = "2023",

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day = "18",

doi = "10.1016/j.jacc.2023.02.027",

language = "English",

volume = "81",

pages = "1459--1470",

journal = "Journal of the American College of Cardiology",

issn = "0735-1097",

publisher = "Elsevier",

number = "15",

}

Holt, A, Strange, JE, Nouhravesh, N, Nielsen, SK, Malik, ME, Schjerning, A-M, Køber, L, Torp-Pedersen, C, Gislason, GH, McGettigan, P, Schou, M & Lamberts, M 2023, 'Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus', Journal of the American College of Cardiology, vol. 81, no. 15, pp. 1459-1470. https://doi.org/10.1016/j.jacc.2023.02.027

TY - JOUR

T1 - Heart Failure Following Anti-Inflammatory Medications in Patients With Type 2 Diabetes Mellitus

AU - Holt, Anders

AU - Strange, Jarl E

AU - Nouhravesh, Nina

AU - Nielsen, Sebastian Kinnberg

AU - Malik, Mariam Elmegaard

AU - Schjerning, Anne-Marie

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H

AU - McGettigan, Patricia

AU - Schou, Morten

AU - Lamberts, Morten

PY - 2023/4/18

Y1 - 2023/4/18

N2 - BACKGROUND: Fluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy.OBJECTIVES: The authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM.METHODS: Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis. Associations between NSAIDs and first-time HF hospitalization were investigated using a case-crossover design with 28-day exposure windows, and ORs with 95% CIs were reported.RESULTS: Included were 331,189 patients with T2DM: 44.2% female, median age of 62 years (IQR: 52-71 years); 23,308 patients were hospitalized with HF during follow-up, and 16% of patients claimed at least 1 NSAID prescription within 1 year. Short-term use of NSAIDs was associated with increased risk of HF hospitalization (OR: 1.43; 95% CI: 1.27-1.63), most notably in subgroups with age ≥80 years (OR: 1.78; 95% CI: 1.39-2.28), elevated hemoglobin (Hb) A1c levels treated with 0 to 1 antidiabetic drug (OR: 1.68; 95% CI: 1.00-2.88), and without previous use of NSAIDs (OR: 2.71; 95% CI: 1.78-4.23).CONCLUSIONS: NSAIDs were widely used and were associated with an increased risk of first-time HF hospitalization in patients with T2DM. Patients with advanced age, elevated HbA1c levels, and new users of NSAID seemed more susceptible. These findings could guide physicians prescribing NSAIDs.

AB - BACKGROUND: Fluid retention and endothelial dysfunction have been related to use of nonsteroidal anti-inflammatory drugs (NSAIDs), and type 2 diabetes mellitus (T2DM) has been linked to both a decline in kidney function and subclinical cardiomyopathy.OBJECTIVES: The authors hypothesized that short-term use of NSAIDs could lead to subsequent development of incident heart failure (HF) in patients with T2DM.METHODS: Using nationwide Danish registers, we identified patients diagnosed with T2DM during 1998 to 2021 and included patients without previous HF, rheumatic disease, or use of NSAIDs 120 days before diagnosis. Associations between NSAIDs and first-time HF hospitalization were investigated using a case-crossover design with 28-day exposure windows, and ORs with 95% CIs were reported.RESULTS: Included were 331,189 patients with T2DM: 44.2% female, median age of 62 years (IQR: 52-71 years); 23,308 patients were hospitalized with HF during follow-up, and 16% of patients claimed at least 1 NSAID prescription within 1 year. Short-term use of NSAIDs was associated with increased risk of HF hospitalization (OR: 1.43; 95% CI: 1.27-1.63), most notably in subgroups with age ≥80 years (OR: 1.78; 95% CI: 1.39-2.28), elevated hemoglobin (Hb) A1c levels treated with 0 to 1 antidiabetic drug (OR: 1.68; 95% CI: 1.00-2.88), and without previous use of NSAIDs (OR: 2.71; 95% CI: 1.78-4.23).CONCLUSIONS: NSAIDs were widely used and were associated with an increased risk of first-time HF hospitalization in patients with T2DM. Patients with advanced age, elevated HbA1c levels, and new users of NSAID seemed more susceptible. These findings could guide physicians prescribing NSAIDs.

KW - Humans

KW - Female

KW - Middle Aged

KW - Aged

KW - Aged, 80 and over

KW - Male

KW - Diabetes Mellitus, Type 2/complications

KW - Anti-Inflammatory Agents, Non-Steroidal/adverse effects

KW - Heart Failure/drug therapy

KW - Vascular Diseases/complications

KW - KEY WORDS heart failure

KW - Type 2 diabetes mellitus

KW - Pharmacoepidemiology

KW - Nonsteroidal anti-inflammatory drug

U2 - 10.1016/j.jacc.2023.02.027

DO - 10.1016/j.jacc.2023.02.027

M3 - Article

C2 - 37045515

SN - 0735-1097

VL - 81

SP - 1459

EP - 1470

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

IS - 15