Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure

Gunnar H Gislason; Jeppe Nørgaard Rasmussen; Steen Zabell Abildstrøm; Tina K Schramm; Morten L Hansen; Emil L Fosbøl; Rikke Sørensen; Fredrik Folke; Pernille Buch; Niels Gadsbøll; Søren Rasmussen; Henrik E Poulsen; Lars Køber; Mette Madsen; Christian Torp-Pedersen; Gunnar H Gislason; Jeppe N Rasmussen; Steen Z Abildstrom; Tina K Schramm; Morten L Hansen; Emil L Fosbøl; Rikke Sørensen; Fredrik Folke; Pernille Buch; Niels Gadsbøll; Søren Poul Lind Rasmussen; Henrik E Poulsen; Lars Køber; Mette Madsen; Christian Torp-Pedersen

doi:10.1001/archinternmed.2008.525

Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure

Gunnar H Gislason, Jeppe Nørgaard Rasmussen, Steen Zabell Abildstrøm, Tina K Schramm, Morten L Hansen, Emil L Fosbøl, Rikke Sørensen, Fredrik Folke, Pernille Buch, Niels Gadsbøll, Søren Rasmussen, Henrik E Poulsen, Lars Køber, Mette Madsen, Christian Torp-Pedersen, Gunnar H Gislason, Jeppe N Rasmussen, Steen Z Abildstrom, Tina K Schramm, Morten L HansenEmil L Fosbøl, Rikke Sørensen, Fredrik Folke, Pernille Buch, Niels Gadsbøll, Søren Poul Lind Rasmussen, Henrik E Poulsen, Lars Køber, Mette Madsen, Christian Torp-Pedersen

212 Citations (Scopus)

Abstract

BACKGROUND: Accumulating evidence indicates increased cardiovascular risk associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in patients with established cardiovascular disease. We studied the risk of death and hospitalization because of acute myocardial infarction and heart failure (HF) associated with use of NSAIDs in an unselected cohort of patients with HF. METHODS: We identified 107,092 patients surviving their first hospitalization because of HF between January 1, 1995, and December 31, 2004, and their subsequent use of NSAIDs from individual-level linkage of nationwide registries of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis was performed using Cox proportional hazard models adjusted for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, and propensity-based risk-stratified models and case-crossover models. RESULTS: A total of 36,354 patients (33.9%) claimed at least 1 prescription of an NSAID after discharge; 60,974 (56.9%) died, and 8970 (8.4%) and 39,984 (37.5%) were hospitalized with myocardial infarction or HF, respectively. The hazard ratio (95% confidence interval) for death was 1.70 (1.58-1.82), 1.75 (1.63-1.88), 1.31 (1.25-1.37), 2.08 (1.95-2.21), 1.22 (1.07-1.39), and 1.28 (1.21-1.35) for rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs, respectively. Furthermore, there was a dose-dependent increase in risk of death and increased risk of hospitalization because of myocardial infarction and HF. Propensity-based risk-stratified analysis and case-crossover models yielded similar results. CONCLUSIONS: NSAIDs are frequently used in patients with HF and are associated with increased risk of death and cardiovascular morbidity. Inasmuch as even commonly used NSAIDs exerted increased risk, the balance between risk and benefit requires careful consideration when any NSAID is given to patients with HF.

Original language	English
Journal	Archives of Internal Medicine
Volume	169
Issue number	2
Pages (from-to)	141-9
Number of pages	8
ISSN	0003-9926
DOIs	https://doi.org/10.1001/archinternmed.2008.525 https://doi.org/10.1001/archinternmed.2008.525
Publication status	Published - 2009

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Gislason, G. H., Rasmussen, J. N., Abildstrøm, S. Z., Schramm, T. K., Hansen, M. L., Fosbøl, E. L., Sørensen, R., Folke, F., Buch, P., Gadsbøll, N., Rasmussen, S., Poulsen, H. E., Køber, L., Madsen, M., Torp-Pedersen, C., Gislason, G. H., Rasmussen, J. N., Abildstrom, S. Z., Schramm, T. K., ... Torp-Pedersen, C. (2009). Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Archives of Internal Medicine, 169(2), 141-9. https://doi.org/10.1001/archinternmed.2008.525, https://doi.org/10.1001/archinternmed.2008.525

Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. / Gislason, Gunnar H; Rasmussen, Jeppe Nørgaard; Abildstrøm, Steen Zabell et al.
In: Archives of Internal Medicine, Vol. 169, No. 2, 2009, p. 141-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Gislason, GH, Rasmussen, JN, Abildstrøm, SZ, Schramm, TK, Hansen, ML, Fosbøl, EL, Sørensen, R, Folke, F, Buch, P, Gadsbøll, N, Rasmussen, S, Poulsen, HE , Køber, L , Madsen, M, Torp-Pedersen, C, Gislason, GH, Rasmussen, JN, Abildstrom, SZ, Schramm, TK, Hansen, ML, Fosbøl, EL, Sørensen, R, Folke, F, Buch, P, Gadsbøll, N, Rasmussen, SPL, Poulsen, HE , Køber, L, Madsen, M & Torp-Pedersen, C 2009, 'Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure', Archives of Internal Medicine, vol. 169, no. 2, pp. 141-9. https://doi.org/10.1001/archinternmed.2008.525, https://doi.org/10.1001/archinternmed.2008.525

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title = "Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure",

abstract = "BACKGROUND: Accumulating evidence indicates increased cardiovascular risk associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in patients with established cardiovascular disease. We studied the risk of death and hospitalization because of acute myocardial infarction and heart failure (HF) associated with use of NSAIDs in an unselected cohort of patients with HF. METHODS: We identified 107,092 patients surviving their first hospitalization because of HF between January 1, 1995, and December 31, 2004, and their subsequent use of NSAIDs from individual-level linkage of nationwide registries of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis was performed using Cox proportional hazard models adjusted for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, and propensity-based risk-stratified models and case-crossover models. RESULTS: A total of 36,354 patients (33.9%) claimed at least 1 prescription of an NSAID after discharge; 60,974 (56.9%) died, and 8970 (8.4%) and 39,984 (37.5%) were hospitalized with myocardial infarction or HF, respectively. The hazard ratio (95% confidence interval) for death was 1.70 (1.58-1.82), 1.75 (1.63-1.88), 1.31 (1.25-1.37), 2.08 (1.95-2.21), 1.22 (1.07-1.39), and 1.28 (1.21-1.35) for rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs, respectively. Furthermore, there was a dose-dependent increase in risk of death and increased risk of hospitalization because of myocardial infarction and HF. Propensity-based risk-stratified analysis and case-crossover models yielded similar results. CONCLUSIONS: NSAIDs are frequently used in patients with HF and are associated with increased risk of death and cardiovascular morbidity. Inasmuch as even commonly used NSAIDs exerted increased risk, the balance between risk and benefit requires careful consideration when any NSAID is given to patients with HF.",

author = "Gislason, {Gunnar H} and Rasmussen, {Jeppe N{\o}rgaard} and Abildstr{\o}m, {Steen Zabell} and Schramm, {Tina K} and Hansen, {Morten L} and Fosb{\o}l, {Emil L} and Rikke S{\o}rensen and Fredrik Folke and Pernille Buch and Niels Gadsb{\o}ll and S{\o}ren Rasmussen and Poulsen, {Henrik E} and Lars K{\o}ber and Mette Madsen and Christian Torp-Pedersen and Gislason, {Gunnar H} and Rasmussen, {Jeppe N} and Abildstrom, {Steen Z} and Schramm, {Tina K} and Hansen, {Morten L} and Fosb{\o}l, {Emil L} and Rikke S{\o}rensen and Fredrik Folke and Pernille Buch and Niels Gadsb{\o}ll and Rasmussen, {S{\o}ren Poul Lind} and Poulsen, {Henrik E} and Lars K{\o}ber and Mette Madsen and Christian Torp-Pedersen",

note = "Keywords: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Risk Factors; Treatment Outcome",

year = "2009",

doi = "10.1001/archinternmed.2008.525",

language = "English",

volume = "169",

pages = "141--9",

journal = "Archives of Internal Medicine",

issn = "0003-9926",

publisher = "The JAMA Network",

number = "2",

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TY - JOUR

T1 - Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure

AU - Gislason, Gunnar H

AU - Rasmussen, Jeppe Nørgaard

AU - Abildstrøm, Steen Zabell

AU - Schramm, Tina K

AU - Hansen, Morten L

AU - Fosbøl, Emil L

AU - Sørensen, Rikke

AU - Folke, Fredrik

AU - Buch, Pernille

AU - Gadsbøll, Niels

AU - Rasmussen, Søren

AU - Poulsen, Henrik E

AU - Køber, Lars

AU - Madsen, Mette

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H

AU - Rasmussen, Jeppe N

AU - Abildstrom, Steen Z

AU - Schramm, Tina K

AU - Hansen, Morten L

AU - Fosbøl, Emil L

AU - Sørensen, Rikke

AU - Folke, Fredrik

AU - Buch, Pernille

AU - Gadsbøll, Niels

AU - Rasmussen, Søren Poul Lind

AU - Poulsen, Henrik E

AU - Køber, Lars

AU - Madsen, Mette

AU - Torp-Pedersen, Christian

N1 - Keywords: Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Female; Heart Failure; Humans; Male; Middle Aged; Myocardial Infarction; Risk Factors; Treatment Outcome

PY - 2009

Y1 - 2009

N2 - BACKGROUND: Accumulating evidence indicates increased cardiovascular risk associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in patients with established cardiovascular disease. We studied the risk of death and hospitalization because of acute myocardial infarction and heart failure (HF) associated with use of NSAIDs in an unselected cohort of patients with HF. METHODS: We identified 107,092 patients surviving their first hospitalization because of HF between January 1, 1995, and December 31, 2004, and their subsequent use of NSAIDs from individual-level linkage of nationwide registries of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis was performed using Cox proportional hazard models adjusted for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, and propensity-based risk-stratified models and case-crossover models. RESULTS: A total of 36,354 patients (33.9%) claimed at least 1 prescription of an NSAID after discharge; 60,974 (56.9%) died, and 8970 (8.4%) and 39,984 (37.5%) were hospitalized with myocardial infarction or HF, respectively. The hazard ratio (95% confidence interval) for death was 1.70 (1.58-1.82), 1.75 (1.63-1.88), 1.31 (1.25-1.37), 2.08 (1.95-2.21), 1.22 (1.07-1.39), and 1.28 (1.21-1.35) for rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs, respectively. Furthermore, there was a dose-dependent increase in risk of death and increased risk of hospitalization because of myocardial infarction and HF. Propensity-based risk-stratified analysis and case-crossover models yielded similar results. CONCLUSIONS: NSAIDs are frequently used in patients with HF and are associated with increased risk of death and cardiovascular morbidity. Inasmuch as even commonly used NSAIDs exerted increased risk, the balance between risk and benefit requires careful consideration when any NSAID is given to patients with HF.

AB - BACKGROUND: Accumulating evidence indicates increased cardiovascular risk associated with nonsteroidal anti-inflammatory drug (NSAID) use, in particular in patients with established cardiovascular disease. We studied the risk of death and hospitalization because of acute myocardial infarction and heart failure (HF) associated with use of NSAIDs in an unselected cohort of patients with HF. METHODS: We identified 107,092 patients surviving their first hospitalization because of HF between January 1, 1995, and December 31, 2004, and their subsequent use of NSAIDs from individual-level linkage of nationwide registries of hospitalization and drug dispensing by pharmacies in Denmark. Data analysis was performed using Cox proportional hazard models adjusted for age, sex, calendar year, comorbidity, medical treatment, and severity of disease, and propensity-based risk-stratified models and case-crossover models. RESULTS: A total of 36,354 patients (33.9%) claimed at least 1 prescription of an NSAID after discharge; 60,974 (56.9%) died, and 8970 (8.4%) and 39,984 (37.5%) were hospitalized with myocardial infarction or HF, respectively. The hazard ratio (95% confidence interval) for death was 1.70 (1.58-1.82), 1.75 (1.63-1.88), 1.31 (1.25-1.37), 2.08 (1.95-2.21), 1.22 (1.07-1.39), and 1.28 (1.21-1.35) for rofecoxib, celecoxib, ibuprofen, diclofenac, naproxen, and other NSAIDs, respectively. Furthermore, there was a dose-dependent increase in risk of death and increased risk of hospitalization because of myocardial infarction and HF. Propensity-based risk-stratified analysis and case-crossover models yielded similar results. CONCLUSIONS: NSAIDs are frequently used in patients with HF and are associated with increased risk of death and cardiovascular morbidity. Inasmuch as even commonly used NSAIDs exerted increased risk, the balance between risk and benefit requires careful consideration when any NSAID is given to patients with HF.

U2 - 10.1001/archinternmed.2008.525

DO - 10.1001/archinternmed.2008.525

M3 - Journal article

C2 - 19171810

SN - 0003-9926

VL - 169

SP - 141

EP - 149

JO - Archives of Internal Medicine

JF - Archives of Internal Medicine

IS - 2

ER -

Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure

Abstract

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