Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study

Anne-Marie Schjerning Olsen; Jesper Lindhardsen; Gunnar H Gislason; Patricia McGettigan; Mark A Hlatky; Emil Fosbøl; Lars Køber; Christian Torp-Pedersen; Morten Lamberts

doi:10.1136/bmj.h5096

Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study

Anne-Marie Schjerning Olsen, Jesper Lindhardsen, Gunnar H Gislason, Patricia McGettigan, Mark A Hlatky, Emil Fosbøl, Lars Køber, Christian Torp-Pedersen, Morten Lamberts

16 Citations (Scopus)

Abstract

STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)?

METHODS: This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models.

STUDY ANSWER AND LIMITATIONS: The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82,955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53,070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35,233) filled at least one prescription for NSAIDs and 45.5% (n=37,771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding.

WHAT THIS STUDY ADDS: In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used.

FUNDING, COMPETING INTERESTS, DATA SHARING: AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation.

Original language	English
Article number	h5096
Journal	B M J
Volume	351
Pages (from-to)	1-6
Number of pages	6
ISSN	0959-8146
DOIs	https://doi.org/10.1136/bmj.h5096
Publication status	Published - 19 Oct 2015

Keywords

Aged
Aged, 80 and over
Anti-Inflammatory Agents, Non-Steroidal
Chemoprevention
Denmark
Drug Therapy, Combination
Female
Fibrinolytic Agents
Gastrointestinal Hemorrhage
Humans
Incidence
Male
Middle Aged
Myocardial Infarction
Outcome Assessment (Health Care)
Proportional Hazards Models
Proton Pump Inhibitors
Registries
Risk Factors

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Schjerning Olsen, A-M., Lindhardsen, J., Gislason, G. H., McGettigan, P., Hlatky, M. A., Fosbøl, E., Køber, L., Torp-Pedersen, C., & Lamberts, M. (2015). Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study. B M J, 351, 1-6. [h5096]. https://doi.org/10.1136/bmj.h5096

Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics : nationwide study. / Schjerning Olsen, Anne-Marie; Lindhardsen, Jesper ; Gislason, Gunnar H et al.

In: B M J, Vol. 351, h5096, 19.10.2015, p. 1-6.

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

Schjerning Olsen, A-M, Lindhardsen, J , Gislason, GH, McGettigan, P, Hlatky, MA, Fosbøl, E, Køber, L, Torp-Pedersen, C & Lamberts, M 2015, 'Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study', B M J, vol. 351, h5096, pp. 1-6. https://doi.org/10.1136/bmj.h5096

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title = "Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study",

abstract = "STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)?METHODS: This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models.STUDY ANSWER AND LIMITATIONS: The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82,955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53,070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35,233) filled at least one prescription for NSAIDs and 45.5% (n=37,771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding.WHAT THIS STUDY ADDS: In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used.FUNDING, COMPETING INTERESTS, DATA SHARING: AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation.",

keywords = "Aged, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal, Chemoprevention, Denmark, Drug Therapy, Combination, Female, Fibrinolytic Agents, Gastrointestinal Hemorrhage, Humans, Incidence, Male, Middle Aged, Myocardial Infarction, Outcome Assessment (Health Care), Proportional Hazards Models, Proton Pump Inhibitors, Registries, Risk Factors",

author = "{Schjerning Olsen}, Anne-Marie and Jesper Lindhardsen and Gislason, {Gunnar H} and Patricia McGettigan and Hlatky, {Mark A} and Emil Fosb{\o}l and Lars K{\o}ber and Christian Torp-Pedersen and Morten Lamberts",

note = "{\textcopyright} Schjerning Olsen et al 2015.",

year = "2015",

month = oct,

day = "19",

doi = "10.1136/bmj.h5096",

language = "English",

volume = "351",

pages = "1--6",

journal = "The BMJ",

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TY - JOUR

T1 - Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics

T2 - nationwide study

AU - Schjerning Olsen, Anne-Marie

AU - Lindhardsen, Jesper

AU - Gislason, Gunnar H

AU - McGettigan, Patricia

AU - Hlatky, Mark A

AU - Fosbøl, Emil

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Lamberts, Morten

N1 - © Schjerning Olsen et al 2015.

PY - 2015/10/19

Y1 - 2015/10/19

N2 - STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)?METHODS: This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models.STUDY ANSWER AND LIMITATIONS: The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82,955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53,070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35,233) filled at least one prescription for NSAIDs and 45.5% (n=37,771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding.WHAT THIS STUDY ADDS: In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used.FUNDING, COMPETING INTERESTS, DATA SHARING: AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation.

AB - STUDY QUESTION: What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)?METHODS: This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models.STUDY ANSWER AND LIMITATIONS: The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82,955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53,070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35,233) filled at least one prescription for NSAIDs and 45.5% (n=37,771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding.WHAT THIS STUDY ADDS: In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used.FUNDING, COMPETING INTERESTS, DATA SHARING: AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation.

KW - Aged

KW - Aged, 80 and over

KW - Anti-Inflammatory Agents, Non-Steroidal

KW - Chemoprevention

KW - Denmark

KW - Drug Therapy, Combination

KW - Female

KW - Fibrinolytic Agents

KW - Gastrointestinal Hemorrhage

KW - Humans

KW - Incidence

KW - Male

KW - Middle Aged

KW - Myocardial Infarction

KW - Outcome Assessment (Health Care)

KW - Proportional Hazards Models

KW - Proton Pump Inhibitors

KW - Registries

KW - Risk Factors

U2 - 10.1136/bmj.h5096

DO - 10.1136/bmj.h5096

M3 - Journal article

C2 - 26481405

SN - 0959-8146

VL - 351

SP - 1

EP - 6

JO - The BMJ

JF - The BMJ

M1 - h5096

ER -