Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals

Emil Loldrup Fosbøl; Fredrik Folke; Søren Jacobsen; Jeppe N Rasmussen; Rikke Sørensen; Tina Ken Schramm; Søren S Andersen; Søren Rasmussen; Henrik Enghusen Poulsen; Lars Køber; Christian Torp-Pedersen; Gunnar H Gislason; Søren Rasmussen

doi:10.1161/circoutcomes.109.861104

Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals

Emil Loldrup Fosbøl, Fredrik Folke, Søren Jacobsen, Jeppe N Rasmussen, Rikke Sørensen, Tina Ken Schramm, Søren S Andersen, Søren Rasmussen, Henrik Enghusen Poulsen, Lars Køber, Christian Torp-Pedersen, Gunnar H Gislason, Søren Rasmussen

126 Citations (Scopus)

Abstract

Background-Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals. Methods and Results-With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously. The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses. The entire Danish population age 10 years or more consisted of 4 614 807 individuals on January 1, 1997, of which 2 663 706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005. Of these; 1 028 437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy. Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63), but naproxen was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42). Conclusions-Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals, whereas our results suggest that naproxen has a safer cardiovascular risk-profile.

Original language	English
Journal	Circulation. Cardiovascular Quality and Outcomes
Volume	3
Issue number	4
Pages (from-to)	395-405
Number of pages	11
DOIs	https://doi.org/10.1161/circoutcomes.109.861104
Publication status	Published - 1 Jul 2010

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10.1161/circoutcomes.109.861104

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Fosbøl, E. L., Folke, F., Jacobsen, S., Rasmussen, J. N., Sørensen, R., Schramm, T. K., Andersen, S. S., Rasmussen, S., Poulsen, H. E., Køber, L., Torp-Pedersen, C., Gislason, G. H., & Rasmussen, S. (2010). Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals. Circulation. Cardiovascular Quality and Outcomes, 3(4), 395-405. https://doi.org/10.1161/circoutcomes.109.861104

Fosbøl, EL, Folke, F , Jacobsen, S, Rasmussen, JN, Sørensen, R, Schramm, TK, Andersen, SS, Rasmussen, S, Poulsen, HE , Køber, L , Torp-Pedersen, C , Gislason, GH & Rasmussen, S 2010, 'Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals', Circulation. Cardiovascular Quality and Outcomes, vol. 3, no. 4, pp. 395-405. https://doi.org/10.1161/circoutcomes.109.861104

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title = "Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals",

abstract = "Background-Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals. Methods and Results-With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously. The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses. The entire Danish population age 10 years or more consisted of 4 614 807 individuals on January 1, 1997, of which 2 663 706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005. Of these; 1 028 437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy. Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63), but naproxen was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42). Conclusions-Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals, whereas our results suggest that naproxen has a safer cardiovascular risk-profile.",

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doi = "10.1161/circoutcomes.109.861104",

language = "English",

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pages = "395--405",

journal = "Circulation. Cardiovascular Quality and Outcomes",

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TY - JOUR

T1 - Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals

AU - Fosbøl, Emil Loldrup

AU - Folke, Fredrik

AU - Jacobsen, Søren

AU - Rasmussen, Jeppe N

AU - Sørensen, Rikke

AU - Schramm, Tina Ken

AU - Andersen, Søren S

AU - Rasmussen, Søren

AU - Poulsen, Henrik Enghusen

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H

AU - Rasmussen, Søren

PY - 2010/7/1

Y1 - 2010/7/1

N2 - Background-Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals. Methods and Results-With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously. The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses. The entire Danish population age 10 years or more consisted of 4 614 807 individuals on January 1, 1997, of which 2 663 706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005. Of these; 1 028 437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy. Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63), but naproxen was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42). Conclusions-Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals, whereas our results suggest that naproxen has a safer cardiovascular risk-profile.

AB - Background-Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals. Methods and Results-With the use of individual-level linkage of nationwide administrative registers, we identified a cohort of individuals without hospitalizations 5 years before first prescription claim of NSAIDs and without claimed drug prescriptions for selected concomitant medication 2 years previously. The risk of cardiovascular death, a composite of coronary death or nonfatal myocardial infarction, and fatal or nonfatal stroke associated with the use of NSAIDs was estimated by case-crossover and Cox proportional hazard analyses. The entire Danish population age 10 years or more consisted of 4 614 807 individuals on January 1, 1997, of which 2 663 706 (57.8%) claimed at least 1 prescription for NSAIDs during 1997 to 2005. Of these; 1 028 437 individuals were included in the study after applying selection criteria regarding comorbidity and concomitant pharmacotherapy. Use of the nonselective NSAID diclofenac and the selective cyclooxygenase-2 inhibitor rofecoxib was associated with an increased risk of cardiovascular death (odds ratio, 1.91; 95% confidence interval, 1.62 to 2.42; and odds ratio, 1.66; 95% confidence interval, 1.06 to 2.59, respectively), with a dose-dependent increase in risk. There was a trend for increased risk of fatal or nonfatal stroke associated with ibuprofen treatment (odds ratio, 1.29; 95% confidence interval, 1.02 to 1.63), but naproxen was not associated with increased cardiovascular risk (odds ratio for cardiovascular death, 0.84; 95% confidence interval, 0.50 to 1.42). Conclusions-Individual NSAIDs have different degrees of cardiovascular safety, which must be considered when choosing appropriate treatment. In particular, rofecoxib and diclofenac were associated with increased cardiovascular mortality and morbidity and should be used with caution in most individuals, whereas our results suggest that naproxen has a safer cardiovascular risk-profile.

U2 - 10.1161/circoutcomes.109.861104

DO - 10.1161/circoutcomes.109.861104

M3 - Journal article

SN - 1941-7705

VL - 3

SP - 395

EP - 405

JO - Circulation. Cardiovascular Quality and Outcomes

JF - Circulation. Cardiovascular Quality and Outcomes

IS - 4

ER -

Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals

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