Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality

Shishir  Rao; Milad Nazarzadeh; Dexter Canoy; Yikuan  Li; Jing  Huang; Mohammad  Mamouei; Gholamreza Salimi-Khorshidi; Aletta E.  Schutte; Bruce Neal; George Davey Smith; Kazem Rahimi

doi:10.1093/eurheartj/ehad535

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality

Shishir Rao^*, Milad Nazarzadeh, Dexter Canoy, Yikuan Li, Jing Huang, Mohammad Mamouei, Gholamreza Salimi-Khorshidi, Aletta E. Schutte, Bruce Neal, George Davey Smith, Kazem Rahimi

^*Corresponding author for this work

Research output: Contribution to journal › Article (Academic Journal) › peer-review

3 Citations (Scopus)

Abstract

Background and Aims
Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined.

Methods
Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non–sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated.

Results
A total of 460 980 and 14 462 patients were identified for the non–sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference −0.04 mmHg (95% confidence interval −0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association.

Conclusions
This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice.

Original language	English
Article number	ehad535
Pages (from-to)	4448-4457
Number of pages	10
Journal	European Heart Journal
Volume	44
Issue number	42
Early online date	23 Aug 2023
DOIs	https://doi.org/10.1093/eurheartj/ehad535
Publication status	Published - 7 Nov 2023

Bibliographical note

Funding Information:
This work was supported by grants by the Global Challenges Research Fund (GCRF: ES/P011055/1), National Institute for Health and Care Research (NIHR) (NIHR: NIHR203982), National Health and Medical Research Council of Australia (NHMRC), Medical Research Future Fund of Australia (MRFF), Medical Research Council (MRC: MC_UU_00011/1), British Heart Foundation (BHF: FS/PhD/21/29110; FS/19/36/34346/BHF), Novo Nordisk, the Oxford Martin School (OMS), University of Oxford, NIHR Bristol Biomedical Research Centre hosted by University Hospitals Bristol and Weston NHS Foundation Trust, and the University of Bristol. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and not necessarily those of BHF, GCRF, NIHR, NHMRC, MRFF, MRC, Novo Nordisk, University of Bristol, Weston NHS Foundation Trust, or the OMS.

Publisher Copyright:
© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

Research Groups and Themes

Bristol Population Health Science Institute

Access to Document

10.1093/eurheartj/ehad535Licence: CC BY

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Persistent link

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal
Gaunt, L. F. (Principal Investigator) & Davey Smith, G. (Principal Investigator)
1/04/18 → 31/03/23
Project: Research

Cite this

@article{33e0597021f3428ea55b0a87778febaa,

title = "Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality",

abstract = "Background and Aims Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. Methods Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non–sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. Results A total of 460 980 and 14 462 patients were identified for the non–sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64\% women). Analysis revealed no difference in SBP [mean difference −0.04 mmHg (95\% confidence interval −0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. Conclusions This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice.",

author = "Shishir Rao and Milad Nazarzadeh and Dexter Canoy and Yikuan Li and Jing Huang and Mohammad Mamouei and Gholamreza Salimi-Khorshidi and Schutte, \{Aletta E.\} and Bruce Neal and \{Davey Smith\}, George and Kazem Rahimi",

note = "Funding Information: This work was supported by grants by the Global Challenges Research Fund (GCRF: ES/P011055/1), National Institute for Health and Care Research (NIHR) (NIHR: NIHR203982), National Health and Medical Research Council of Australia (NHMRC), Medical Research Future Fund of Australia (MRFF), Medical Research Council (MRC: MC\_UU\_00011/1), British Heart Foundation (BHF: FS/PhD/21/29110; FS/19/36/34346/BHF), Novo Nordisk, the Oxford Martin School (OMS), University of Oxford, NIHR Bristol Biomedical Research Centre hosted by University Hospitals Bristol and Weston NHS Foundation Trust, and the University of Bristol. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and not necessarily those of BHF, GCRF, NIHR, NHMRC, MRFF, MRC, Novo Nordisk, University of Bristol, Weston NHS Foundation Trust, or the OMS. Publisher Copyright: {\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.",

year = "2023",

month = nov,

day = "7",

doi = "10.1093/eurheartj/ehad535",

language = "English",

volume = "44",

pages = "4448--4457",

journal = "European Heart Journal",

issn = "0195-668X",

publisher = "Oxford University Press",

number = "42",

}

TY - JOUR

T1 - Sodium-based paracetamol

T2 - impact on blood pressure, cardiovascular events, and all-cause mortality

AU - Rao, Shishir

AU - Nazarzadeh, Milad

AU - Canoy, Dexter

AU - Li, Yikuan

AU - Huang, Jing

AU - Mamouei, Mohammad

AU - Salimi-Khorshidi, Gholamreza

AU - Schutte, Aletta E.

AU - Neal, Bruce

AU - Davey Smith, George

AU - Rahimi, Kazem

N1 - Funding Information: This work was supported by grants by the Global Challenges Research Fund (GCRF: ES/P011055/1), National Institute for Health and Care Research (NIHR) (NIHR: NIHR203982), National Health and Medical Research Council of Australia (NHMRC), Medical Research Future Fund of Australia (MRFF), Medical Research Council (MRC: MC_UU_00011/1), British Heart Foundation (BHF: FS/PhD/21/29110; FS/19/36/34346/BHF), Novo Nordisk, the Oxford Martin School (OMS), University of Oxford, NIHR Bristol Biomedical Research Centre hosted by University Hospitals Bristol and Weston NHS Foundation Trust, and the University of Bristol. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views expressed are those of the authors and not necessarily those of BHF, GCRF, NIHR, NHMRC, MRFF, MRC, Novo Nordisk, University of Bristol, Weston NHS Foundation Trust, or the OMS. Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.

PY - 2023/11/7

Y1 - 2023/11/7

N2 - Background and Aims Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. Methods Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non–sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. Results A total of 460 980 and 14 462 patients were identified for the non–sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference −0.04 mmHg (95% confidence interval −0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. Conclusions This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice.

AB - Background and Aims Effervescent formulations of paracetamol containing sodium bicarbonate have been reported to associate with increased blood pressure and a higher risk of cardiovascular diseases and all-cause mortality. Given the major implications of these findings, the reported associations were re-examined. Methods Using linked electronic health records data, a cohort of 475 442 UK individuals with at least one prescription of paracetamol, aged between 60 and 90 years, was identified. Outcomes in patients taking sodium-based paracetamol were compared with those taking non–sodium-based formulations of the same. Using a deep learning approach, associations with systolic blood pressure (SBP), major cardiovascular events (myocardial infarction, heart failure, and stroke), and all-cause mortality within 1 year after baseline were investigated. Results A total of 460 980 and 14 462 patients were identified for the non–sodium-based and sodium-based paracetamol exposure groups, respectively (mean age: 74 years; 64% women). Analysis revealed no difference in SBP [mean difference −0.04 mmHg (95% confidence interval −0.51, 0.43)] and no association with major cardiovascular events [relative risk (RR) 1.03 (0.91, 1.16)]. Sodium-based paracetamol showed a positive association with all-cause mortality [RR 1.46 (1.40, 1.52)]. However, after further accounting of other sources of residual confounding, the observed association attenuated towards the null [RR 1.08 (1.01, 1.16)]. Exploratory analyses revealed dysphagia and related conditions as major sources of uncontrolled confounding by indication for this association. Conclusions This study does not support previous suggestions of increased SBP and an elevated risk of cardiovascular events from short-term use of sodium bicarbonate paracetamol in routine clinical practice.

U2 - 10.1093/eurheartj/ehad535

DO - 10.1093/eurheartj/ehad535

M3 - Article (Academic Journal)

C2 - 37611115

SN - 0195-668X

VL - 44

SP - 4448

EP - 4457

JO - European Heart Journal

JF - European Heart Journal

IS - 42

M1 - ehad535

ER -

Sodium-based paracetamol: impact on blood pressure, cardiovascular events, and all-cause mortality

Abstract

Bibliographical note

Research Groups and Themes

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Projects

IEU: MRC Integrative Epidemiology Unit Quinquennial renewal

Cite this