Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study

Morten Lamberts; Gregory Y H Lip; Morten Lock Hansen; Jesper Lindhardsen; Jonas Bjerring Olesen; Jakob Raunsø; Anne-Marie Schjerning Olsen; Per Kragh Andersen; Thomas Alexander Gerds; Emil L Fosbøl; Christian Torp-Pedersen; Gunnar H Gislason

doi:10.7326/M13-1581

Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study

Morten Lamberts, Gregory Y H Lip, Morten Lock Hansen, Jesper Lindhardsen, Jonas Bjerring Olesen, Jakob Raunsø, Anne-Marie Schjerning Olsen, Per Kragh Andersen, Thomas Alexander Gerds, Emil L Fosbøl, Christian Torp-Pedersen, Gunnar H Gislason

Cardiovascular Sciences

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

68 Citations (Scopus)

Abstract

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown.

OBJECTIVE: To investigate the risk for serious bleeding and thromboembolism associated with ongoing NSAID and antithrombotic therapy.

DESIGN: Observational cohort study.

SETTING: Nationwide registries.

PATIENTS: Danish patients with AF hospitalized between 1997 and 2011.

MEASUREMENTS: Absolute risk for serious bleeding and thromboembolism with ongoing NSAID and antithrombotic therapy, assessed by using Cox models.

RESULTS: Of 150 900 patients with AF (median age, 75 years [interquartile range, 65 to 83 years]; 47% female), 53 732 (35.6%) were prescribed an NSAID during a median follow-up of 6.2 years (interquartile range, 2.1 to 14.0 years). There were 17 187 (11.4%) and 19 561 (13.0%) occurrences of serious bleeding and thromboembolism, respectively. At 3 months, the absolute risk for serious bleeding within 14 days of NSAID exposure was 3.5 events per 1000 patients compared with 1.5 events per 1000 patients without NSAID exposure. The risk difference was 1.9 events per 1000 patients. In patients selected for oral anticoagulant therapy, the absolute risk difference was 2.5 events per 1000 patients. Use of NSAIDs was associated with increased absolute risks for serious bleeding and thromboembolism across all antithrombotic regimens and NSAID types. An NSAID dosage above the recommended minimum was associated with a substantially increased hazard ratio for bleeding.

LIMITATION: Observational design and unmeasured confounders.

CONCLUSION: Use of NSAIDs was associated with an independent risk for serious bleeding and thromboembolism in patients with AF. Short-term NSAID exposure was associated with increased bleeding risk. Physicians should exercise caution with NSAIDs in patients with AF.

PRIMARY FUNDING SOURCE: None.

Original language	English
Pages (from-to)	690-8
Number of pages	9
Journal	Annals of internal medicine
Volume	161
Issue number	10
DOIs	https://doi.org/10.7326/M13-1581
Publication status	Published - 18 Nov 2014

Keywords

Adult
Aged
Aged, 80 and over
Anti-Inflammatory Agents, Non-Steroidal
Atrial Fibrillation
Cohort Studies
Denmark
Drug Interactions
Female
Fibrinolytic Agents
Hemorrhage
Hospitalization
Humans
Male
Middle Aged
Registries
Thromboembolism

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10.7326/M13-1581

Cite this

Lamberts, M., Lip, G. Y. H., Hansen, M. L., Lindhardsen, J., Olesen, J. B., Raunsø, J., Olsen, A-M. S., Andersen, P. K., Gerds, T. A., Fosbøl, E. L., Torp-Pedersen, C., & Gislason, G. H. (2014). Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. Annals of internal medicine, 161(10), 690-8. https://doi.org/10.7326/M13-1581

@article{22028063529c4bd4a61a46d9a78c3279,

title = "Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study",

abstract = "BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown.OBJECTIVE: To investigate the risk for serious bleeding and thromboembolism associated with ongoing NSAID and antithrombotic therapy.DESIGN: Observational cohort study.SETTING: Nationwide registries.PATIENTS: Danish patients with AF hospitalized between 1997 and 2011.MEASUREMENTS: Absolute risk for serious bleeding and thromboembolism with ongoing NSAID and antithrombotic therapy, assessed by using Cox models.RESULTS: Of 150 900 patients with AF (median age, 75 years [interquartile range, 65 to 83 years]; 47% female), 53 732 (35.6%) were prescribed an NSAID during a median follow-up of 6.2 years (interquartile range, 2.1 to 14.0 years). There were 17 187 (11.4%) and 19 561 (13.0%) occurrences of serious bleeding and thromboembolism, respectively. At 3 months, the absolute risk for serious bleeding within 14 days of NSAID exposure was 3.5 events per 1000 patients compared with 1.5 events per 1000 patients without NSAID exposure. The risk difference was 1.9 events per 1000 patients. In patients selected for oral anticoagulant therapy, the absolute risk difference was 2.5 events per 1000 patients. Use of NSAIDs was associated with increased absolute risks for serious bleeding and thromboembolism across all antithrombotic regimens and NSAID types. An NSAID dosage above the recommended minimum was associated with a substantially increased hazard ratio for bleeding.LIMITATION: Observational design and unmeasured confounders.CONCLUSION: Use of NSAIDs was associated with an independent risk for serious bleeding and thromboembolism in patients with AF. Short-term NSAID exposure was associated with increased bleeding risk. Physicians should exercise caution with NSAIDs in patients with AF.PRIMARY FUNDING SOURCE: None.",

keywords = "Adult, Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal, Atrial Fibrillation, Cohort Studies, Denmark, Drug Interactions, Female, Fibrinolytic Agents, Hemorrhage, Hospitalization, Humans, Male, Middle Aged, Registries, Thromboembolism",

author = "Morten Lamberts and Lip, {Gregory Y H} and Hansen, {Morten Lock} and Jesper Lindhardsen and Olesen, {Jonas Bjerring} and Jakob Rauns{\o} and Olsen, {Anne-Marie Schjerning} and Andersen, {Per Kragh} and Gerds, {Thomas Alexander} and Fosb{\o}l, {Emil L} and Christian Torp-Pedersen and Gislason, {Gunnar H}",

year = "2014",

month = nov,

day = "18",

doi = "10.7326/M13-1581",

language = "English",

volume = "161",

pages = "690--8",

journal = "Annals of internal medicine",

issn = "0003-4819",

publisher = "American College of Physicians",

number = "10",

}

Lamberts, M, Lip, GYH, Hansen, ML, Lindhardsen, J, Olesen, JB, Raunsø, J, Olsen, A-MS, Andersen, PK, Gerds, TA, Fosbøl, EL, Torp-Pedersen, C & Gislason, GH 2014, 'Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study', Annals of internal medicine, vol. 161, no. 10, pp. 690-8. https://doi.org/10.7326/M13-1581

Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study. / Lamberts, Morten; Lip, Gregory Y H; Hansen, Morten Lock et al.
In: Annals of internal medicine, Vol. 161, No. 10, 18.11.2014, p. 690-8.

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

TY - JOUR

T1 - Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy

T2 - a nationwide cohort study

AU - Lamberts, Morten

AU - Lip, Gregory Y H

AU - Hansen, Morten Lock

AU - Lindhardsen, Jesper

AU - Olesen, Jonas Bjerring

AU - Raunsø, Jakob

AU - Olsen, Anne-Marie Schjerning

AU - Andersen, Per Kragh

AU - Gerds, Thomas Alexander

AU - Fosbøl, Emil L

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar H

PY - 2014/11/18

Y1 - 2014/11/18

N2 - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown.OBJECTIVE: To investigate the risk for serious bleeding and thromboembolism associated with ongoing NSAID and antithrombotic therapy.DESIGN: Observational cohort study.SETTING: Nationwide registries.PATIENTS: Danish patients with AF hospitalized between 1997 and 2011.MEASUREMENTS: Absolute risk for serious bleeding and thromboembolism with ongoing NSAID and antithrombotic therapy, assessed by using Cox models.RESULTS: Of 150 900 patients with AF (median age, 75 years [interquartile range, 65 to 83 years]; 47% female), 53 732 (35.6%) were prescribed an NSAID during a median follow-up of 6.2 years (interquartile range, 2.1 to 14.0 years). There were 17 187 (11.4%) and 19 561 (13.0%) occurrences of serious bleeding and thromboembolism, respectively. At 3 months, the absolute risk for serious bleeding within 14 days of NSAID exposure was 3.5 events per 1000 patients compared with 1.5 events per 1000 patients without NSAID exposure. The risk difference was 1.9 events per 1000 patients. In patients selected for oral anticoagulant therapy, the absolute risk difference was 2.5 events per 1000 patients. Use of NSAIDs was associated with increased absolute risks for serious bleeding and thromboembolism across all antithrombotic regimens and NSAID types. An NSAID dosage above the recommended minimum was associated with a substantially increased hazard ratio for bleeding.LIMITATION: Observational design and unmeasured confounders.CONCLUSION: Use of NSAIDs was associated with an independent risk for serious bleeding and thromboembolism in patients with AF. Short-term NSAID exposure was associated with increased bleeding risk. Physicians should exercise caution with NSAIDs in patients with AF.PRIMARY FUNDING SOURCE: None.

AB - BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are assumed to increase bleeding risk, but their actual relation to serious bleeding in patients with atrial fibrillation (AF) who are receiving antithrombotic medication is unknown.OBJECTIVE: To investigate the risk for serious bleeding and thromboembolism associated with ongoing NSAID and antithrombotic therapy.DESIGN: Observational cohort study.SETTING: Nationwide registries.PATIENTS: Danish patients with AF hospitalized between 1997 and 2011.MEASUREMENTS: Absolute risk for serious bleeding and thromboembolism with ongoing NSAID and antithrombotic therapy, assessed by using Cox models.RESULTS: Of 150 900 patients with AF (median age, 75 years [interquartile range, 65 to 83 years]; 47% female), 53 732 (35.6%) were prescribed an NSAID during a median follow-up of 6.2 years (interquartile range, 2.1 to 14.0 years). There were 17 187 (11.4%) and 19 561 (13.0%) occurrences of serious bleeding and thromboembolism, respectively. At 3 months, the absolute risk for serious bleeding within 14 days of NSAID exposure was 3.5 events per 1000 patients compared with 1.5 events per 1000 patients without NSAID exposure. The risk difference was 1.9 events per 1000 patients. In patients selected for oral anticoagulant therapy, the absolute risk difference was 2.5 events per 1000 patients. Use of NSAIDs was associated with increased absolute risks for serious bleeding and thromboembolism across all antithrombotic regimens and NSAID types. An NSAID dosage above the recommended minimum was associated with a substantially increased hazard ratio for bleeding.LIMITATION: Observational design and unmeasured confounders.CONCLUSION: Use of NSAIDs was associated with an independent risk for serious bleeding and thromboembolism in patients with AF. Short-term NSAID exposure was associated with increased bleeding risk. Physicians should exercise caution with NSAIDs in patients with AF.PRIMARY FUNDING SOURCE: None.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Atrial Fibrillation

KW - Cohort Studies

KW - Denmark

KW - Drug Interactions

KW - Female

KW - Fibrinolytic Agents

KW - Hemorrhage

KW - Hospitalization

KW - Humans

KW - Male

KW - Middle Aged

KW - Registries

KW - Thromboembolism

U2 - 10.7326/M13-1581

DO - 10.7326/M13-1581

M3 - Article

C2 - 25402512

SN - 0003-4819

VL - 161

SP - 690

EP - 698

JO - Annals of internal medicine

JF - Annals of internal medicine

IS - 10

ER -

Relation of nonsteroidal anti-inflammatory drugs to serious bleeding and thromboembolism risk in patients with atrial fibrillation receiving antithrombotic therapy: a nationwide cohort study

Abstract

Keywords

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