Association of Tramadol vs Codeine Prescription Dispensation with Mortality and Other Adverse Clinical Outcomes
(2021) In JAMA - Journal of the American Medical Association 326(15). p.1504-1515- Abstract
Importance: Although tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids. Objective: To assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings. Design, Setting, and Participants: Retrospective, population-based, propensity score-matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31,... (More)
Importance: Although tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids. Objective: To assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings. Design, Setting, and Participants: Retrospective, population-based, propensity score-matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31, 2017. Exposures: New prescription dispensation of tramadol or codeine (no dispensation in the previous year). Main Outcomes and Measures: Outcomes studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse/dependence, and sleep disorders within 1 year after the first dispensation. Absolute rate differences (ARDs) and hazard ratios (HRs) with 95% confidence intervals were calculated using cause-specific Cox models. Results: Of the 1093064 patients with a tramadol or codeine dispensation during the study period (326921 for tramadol, 762492 for codeine, 3651 for both drugs concomitantly), a total of 368960 patients (184480 propensity score-matched pairs) were included after study exclusions and propensity score matching (mean age, 53.1 [SD, 16.1] years; 57.3% women). Compared with codeine, tramadol dispensation was significantly associated with a higher risk of all-cause mortality (incidence, 13.00 vs 5.61 per 1000 person-years; HR, 2.31 [95% CI, 2.08-2.56]; ARD, 7.37 [95% CI, 6.09-8.78] per 1000 person-years), cardiovascular events (incidence, 10.03 vs 8.67 per 1000 person-years; HR, 1.15 [95% CI, 1.05-1.27]; ARD, 1.36 [95% CI, 0.45-2.36] per 1000 person-years), and fractures (incidence, 12.26 vs 8.13 per 1000 person-years; HR, 1.50 [95% CI, 1.37-1.65]; ARD, 4.10 [95% CI, 3.02-5.29] per 1000 person-years). No significant difference was observed for the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders. Conclusions and Relevance: In this population-based cohort study, a new prescription dispensation of tramadol, compared with codeine, was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders. The findings should be interpreted cautiously, given the potential for residual confounding..
(Less)
- author
- Xie, Junqing
; Strauss, Victoria Y.
; Martinez-Laguna, Daniel
; Carbonell-Abella, Cristina
; Diez-Perez, Adolfo
; Nogues, Xavier
; Collins, Gary S.
; Khalid, Sara
; Delmestri, Antonella
; Turkiewicz, Aleksandra
LU
; Englund, Martin
LU
; Tadrous, Mina
; Reyes, Carlen
and Prieto-Alhambra, Daniel
(Less) - organization
- publishing date
- 2021-10-19
- type
- Contribution to journal
- publication status
- published
- subject
- in
- JAMA - Journal of the American Medical Association
- volume
- 326
- issue
- 15
- pages
- 12 pages
- publisher
- American Medical Association
- external identifiers
-
- pmid:34665205
- scopus:85117856385
- ISSN
- 0098-7484
- DOI
- 10.1001/jama.2021.15255
- language
- English
- LU publication?
- yes
- additional info
- Publisher Copyright: © 2021 American Medical Association. All rights reserved.
- id
- 125a30e5-841f-4df4-a60f-2b815dc9cbbf
- date added to LUP
- 2021-11-23 13:49:52
- date last changed
- 2025-03-09 22:46:10
@article{125a30e5-841f-4df4-a60f-2b815dc9cbbf,
abstract = {{<p>Importance: Although tramadol is increasingly used to manage chronic noncancer pain, few safety studies have compared it with other opioids. Objective: To assess the associations of tramadol, compared with codeine, with mortality and other adverse clinical outcomes as used in outpatient settings. Design, Setting, and Participants: Retrospective, population-based, propensity score-matched cohort study using a primary care database with routinely collected medical records and pharmacy dispensations covering more than 80% of the population of Catalonia, Spain (≈6 million people). Patients 18 years or older with 1 or more year of available data and dispensation of tramadol or codeine (2007-2017) were included and followed up to December 31, 2017. Exposures: New prescription dispensation of tramadol or codeine (no dispensation in the previous year). Main Outcomes and Measures: Outcomes studied were all-cause mortality, cardiovascular events, fractures, constipation, delirium, falls, opioid abuse/dependence, and sleep disorders within 1 year after the first dispensation. Absolute rate differences (ARDs) and hazard ratios (HRs) with 95% confidence intervals were calculated using cause-specific Cox models. Results: Of the 1093064 patients with a tramadol or codeine dispensation during the study period (326921 for tramadol, 762492 for codeine, 3651 for both drugs concomitantly), a total of 368960 patients (184480 propensity score-matched pairs) were included after study exclusions and propensity score matching (mean age, 53.1 [SD, 16.1] years; 57.3% women). Compared with codeine, tramadol dispensation was significantly associated with a higher risk of all-cause mortality (incidence, 13.00 vs 5.61 per 1000 person-years; HR, 2.31 [95% CI, 2.08-2.56]; ARD, 7.37 [95% CI, 6.09-8.78] per 1000 person-years), cardiovascular events (incidence, 10.03 vs 8.67 per 1000 person-years; HR, 1.15 [95% CI, 1.05-1.27]; ARD, 1.36 [95% CI, 0.45-2.36] per 1000 person-years), and fractures (incidence, 12.26 vs 8.13 per 1000 person-years; HR, 1.50 [95% CI, 1.37-1.65]; ARD, 4.10 [95% CI, 3.02-5.29] per 1000 person-years). No significant difference was observed for the risk of falls, delirium, constipation, opioid abuse/dependence, or sleep disorders. Conclusions and Relevance: In this population-based cohort study, a new prescription dispensation of tramadol, compared with codeine, was significantly associated with a higher risk of subsequent all-cause mortality, cardiovascular events, and fractures, but there was no significant difference in the risk of constipation, delirium, falls, opioid abuse/dependence, or sleep disorders. The findings should be interpreted cautiously, given the potential for residual confounding..</p>}},
author = {{Xie, Junqing and Strauss, Victoria Y. and Martinez-Laguna, Daniel and Carbonell-Abella, Cristina and Diez-Perez, Adolfo and Nogues, Xavier and Collins, Gary S. and Khalid, Sara and Delmestri, Antonella and Turkiewicz, Aleksandra and Englund, Martin and Tadrous, Mina and Reyes, Carlen and Prieto-Alhambra, Daniel}},
issn = {{0098-7484}},
language = {{eng}},
month = {{10}},
number = {{15}},
pages = {{1504--1515}},
publisher = {{American Medical Association}},
series = {{JAMA - Journal of the American Medical Association}},
title = {{Association of Tramadol vs Codeine Prescription Dispensation with Mortality and Other Adverse Clinical Outcomes}},
url = {{http://dx.doi.org/10.1001/jama.2021.15255}},
doi = {{10.1001/jama.2021.15255}},
volume = {{326}},
year = {{2021}},
}