Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study

Mette Charlot; Ole Ahlehoff; Mette Lykke Norgaard; Casper H Jørgensen; Rikke Sørensen; Steen Z Abildstrøm; Peter Riis Hansen; Jan Kyst Madsen; Lars Køber; Christian Torp-Pedersen; Gunnar Gislason; Mette Lykke Norgaard; Rikke Sørensen

doi:http://dx.doi.org/10.1059/0003-4819-153-6-201009210-00005

Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study

Mette Charlot, Ole Ahlehoff, Mette Lykke Norgaard, Casper H Jørgensen, Rikke Sørensen, Steen Z Abildstrøm, Peter Riis Hansen, Jan Kyst Madsen, Lars Køber, Christian Torp-Pedersen, Gunnar Gislason, Mette Lykke Norgaard, Rikke Sørensen

212 Citationer (Scopus)

Abstract

Background: Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. Objective: To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction. Design: A nationwide cohort study based on linked administrative registry data. Setting: All hospitals in Denmark. Patients: All patients discharged after first-time myocardial infarction from 2000 to 2006. Measurements: The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year. Results: Of 56 406 included patients, 9137 (16.2%) were rehospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72). Limitations: Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. Conclusion: Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone. Primary Funding Source: The Danish Medical Research Council and the Danish Heart Foundation.

Originalsprog	Engelsk
Tidsskrift	Annals of Internal Medicine
Vol/bind	153
Udgave nummer	6
Sider (fra-til)	378-86
Antal sider	9
ISSN	0003-4819
DOI	https://doi.org/10.1059/0003-4819-153-6-201009210-00005
Status	Udgivet - 21 sep. 2010

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http://dx.doi.org/10.1059/0003-4819-153-6-201009210-00005

Citationsformater

Charlot, M., Ahlehoff, O., Norgaard, M. L., Jørgensen, C. H., Sørensen, R., Abildstrøm, S. Z., Hansen, P. R., Madsen, J. K., Køber, L., Torp-Pedersen, C., Gislason, G., Norgaard, M. L., & Sørensen, R. (2010). Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study. Annals of Internal Medicine, 153(6), 378-86. https://doi.org/10.1059/0003-4819-153-6-201009210-00005

Charlot, M, Ahlehoff, O, Norgaard, ML, Jørgensen, CH, Sørensen, R, Abildstrøm, SZ, Hansen, PR, Madsen, JK, Køber, L , Torp-Pedersen, C , Gislason, G, Norgaard, ML & Sørensen, R 2010, 'Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study', Annals of Internal Medicine, bind 153, nr. 6, s. 378-86. https://doi.org/10.1059/0003-4819-153-6-201009210-00005

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title = "Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study",

abstract = "Background: Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. Objective: To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction. Design: A nationwide cohort study based on linked administrative registry data. Setting: All hospitals in Denmark. Patients: All patients discharged after first-time myocardial infarction from 2000 to 2006. Measurements: The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year. Results: Of 56 406 included patients, 9137 (16.2%) were rehospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72). Limitations: Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. Conclusion: Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone. Primary Funding Source: The Danish Medical Research Council and the Danish Heart Foundation.",

author = "Mette Charlot and Ole Ahlehoff and Norgaard, {Mette Lykke} and J{\o}rgensen, {Casper H} and Rikke S{\o}rensen and Abildstr{\o}m, {Steen Z} and Hansen, {Peter Riis} and Madsen, {Jan Kyst} and Lars K{\o}ber and Christian Torp-Pedersen and Gunnar Gislason and Norgaard, {Mette Lykke} and Rikke S{\o}rensen",

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doi = "http://dx.doi.org/10.1059/0003-4819-153-6-201009210-00005",

language = "English",

volume = "153",

pages = "378--86",

journal = "Annals of Internal Medicine",

issn = "0003-4819",

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TY - JOUR

T1 - Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study

AU - Charlot, Mette

AU - Ahlehoff, Ole

AU - Norgaard, Mette Lykke

AU - Jørgensen, Casper H

AU - Sørensen, Rikke

AU - Abildstrøm, Steen Z

AU - Hansen, Peter Riis

AU - Madsen, Jan Kyst

AU - Køber, Lars

AU - Torp-Pedersen, Christian

AU - Gislason, Gunnar

AU - Norgaard, Mette Lykke

AU - Sørensen, Rikke

PY - 2010/9/21

Y1 - 2010/9/21

N2 - Background: Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. Objective: To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction. Design: A nationwide cohort study based on linked administrative registry data. Setting: All hospitals in Denmark. Patients: All patients discharged after first-time myocardial infarction from 2000 to 2006. Measurements: The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year. Results: Of 56 406 included patients, 9137 (16.2%) were rehospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72). Limitations: Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. Conclusion: Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone. Primary Funding Source: The Danish Medical Research Council and the Danish Heart Foundation.

AB - Background: Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. Objective: To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction. Design: A nationwide cohort study based on linked administrative registry data. Setting: All hospitals in Denmark. Patients: All patients discharged after first-time myocardial infarction from 2000 to 2006. Measurements: The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year. Results: Of 56 406 included patients, 9137 (16.2%) were rehospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72). Limitations: Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. Conclusion: Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone. Primary Funding Source: The Danish Medical Research Council and the Danish Heart Foundation.

U2 - http://dx.doi.org/10.1059/0003-4819-153-6-201009210-00005

DO - http://dx.doi.org/10.1059/0003-4819-153-6-201009210-00005

M3 - Journal article

SN - 0003-4819

VL - 153

SP - 378

EP - 386

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

IS - 6

ER -

Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study

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