The University of Southampton
University of Southampton Institutional Repository

Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records

Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records
Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records

Background: macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use.

Methodology: observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia. 

Results: analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed. No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular. 

Conclusions: although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks.

0300-0729
252-260
Williamson, E.
074d92d7-64ed-4666-abef-f07ebd0eb66c
Denaxas, S.
65af3da2-30fd-4d09-bdb2-81abfd3f430c
Morris, S.
f04d0062-0e4d-418c-8640-737d722832a3
Clarke, C. S.
ecc070e4-31d9-42f4-8104-77be07561b58
Thomas, M.
997c78e0-3849-4ce8-b1bc-86ebbdee3953
Evans, H.
3c15a1cd-e3db-49de-b2b8-89f5af180efb
Direk, K.
d89b2f7d-04c1-4568-b50c-b6151d9650e3
Gonzalez-Izquierdo, A.
95657cc9-9f19-44a2-9562-760a67650abb
Little, P.
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Lund, V.
19b0121c-1518-4cd8-8c2b-be8557320b0f
Blackshaw, H.
89f97306-9bba-42b3-a09f-4574d08bd711
Schilder, A.
4efe172e-cbc9-4d1b-b089-f293f5c626ef
Philpott, C.
3b9f988c-a61e-4736-9b69-6697fb2cdc5b
Hopkins, C.
2f212158-65e9-4d25-abfb-b81e4314021c
Carpenter, J.
f711dd60-8725-4ce8-8d27-04ad03fc6850
Programme Team, On Behalf Of The Macro
d13c93cd-29cd-4f21-b0af-c0280e1c7a2d
Williamson, E.
074d92d7-64ed-4666-abef-f07ebd0eb66c
Denaxas, S.
65af3da2-30fd-4d09-bdb2-81abfd3f430c
Morris, S.
f04d0062-0e4d-418c-8640-737d722832a3
Clarke, C. S.
ecc070e4-31d9-42f4-8104-77be07561b58
Thomas, M.
997c78e0-3849-4ce8-b1bc-86ebbdee3953
Evans, H.
3c15a1cd-e3db-49de-b2b8-89f5af180efb
Direk, K.
d89b2f7d-04c1-4568-b50c-b6151d9650e3
Gonzalez-Izquierdo, A.
95657cc9-9f19-44a2-9562-760a67650abb
Little, P.
1bf2d1f7-200c-47a5-ab16-fe5a8756a777
Lund, V.
19b0121c-1518-4cd8-8c2b-be8557320b0f
Blackshaw, H.
89f97306-9bba-42b3-a09f-4574d08bd711
Schilder, A.
4efe172e-cbc9-4d1b-b089-f293f5c626ef
Philpott, C.
3b9f988c-a61e-4736-9b69-6697fb2cdc5b
Hopkins, C.
2f212158-65e9-4d25-abfb-b81e4314021c
Carpenter, J.
f711dd60-8725-4ce8-8d27-04ad03fc6850
Programme Team, On Behalf Of The Macro
d13c93cd-29cd-4f21-b0af-c0280e1c7a2d

Williamson, E., Denaxas, S., Morris, S., Clarke, C. S., Thomas, M., Evans, H., Direk, K., Gonzalez-Izquierdo, A., Little, P., Lund, V., Blackshaw, H., Schilder, A., Philpott, C., Hopkins, C., Carpenter, J. and Programme Team, On Behalf Of The Macro (2019) Risk of mortality and cardiovascular events following macrolide prescription in chronic rhinosinusitis patients: a cohort study using linked primary care electronic health records. Rhinology, 57 (4), 252-260. (doi:10.4193/Rhin18.237).

Record type: Article

Abstract

Background: macrolide antibiotics have demonstrated important anti-inflammatory and immunomodulatory properties in chronic rhinosinusitis (CRS) patients. However, reports of increased risks of cardiovascular events have led to safety concerns. We investigated the risk of all-cause and cardiac death, and cardiovascular outcomes, associated with macrolide use.

Methodology: observational cohort (1997-2016) using linked data from the Clinical Practice Research Datalink, Hospital Episodes Statistics, and the Office for National Statistics. Patients aged 16-80 years with CRS prescribed a macrolide antibiotic or penicillin were included, comparing prescriptions for macrolide antibiotics to penicillin. Outcomes were all-cause mortality, cardiac death, myocardial infarction, stroke, diagnosis of peripheral vascular disease, and cardiac arrhythmia. 

Results: analysis included 320,798 prescriptions received by 66,331 patients. There were 3,251 deaths, 815 due to cardiovascular causes, 925 incident myocardial infarctions, 859 strokes, 637 diagnoses of peripheral vascular disease, and 1,436 cardiac arrhythmias. A non-statistically significant trend towards increased risk of myocardial infarction during the first 30 days following macrolide prescription was observed. No statistically significant short- or long-term risks were observed for macrolide prescription. No significant risks were identified for clarithromycin in particular. 

Conclusions: although not statistically significant, our best estimates suggest an increased short-term risk of myocardial infarction in patients with CRS following macrolide prescription, supporting previous observational evidence. However, confounding by indication remains a possible explanation for this apparent increased risk. We found no evidence of longer term increased risks.

Text
MACRO macrolide safety paper - Accepted Manuscript
Download (204kB)

More information

e-pub ahead of print date: 1 August 2019

Identifiers

Local EPrints ID: 435756
URI: http://eprints.soton.ac.uk/id/eprint/435756
ISSN: 0300-0729
PURE UUID: 6ed1c0d4-c518-44f0-977e-d694f53721ea

Catalogue record

Date deposited: 19 Nov 2019 17:30
Last modified: 19 Nov 2019 17:30

Export record

Altmetrics

Contributors

Author: E. Williamson
Author: S. Denaxas
Author: S. Morris
Author: C. S. Clarke
Author: M. Thomas
Author: H. Evans
Author: K. Direk
Author: A. Gonzalez-Izquierdo
Author: P. Little
Author: V. Lund
Author: H. Blackshaw
Author: A. Schilder
Author: C. Philpott
Author: C. Hopkins
Author: J. Carpenter
Author: On Behalf Of The Macro Programme Team

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×