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Long-Term Risk of Cardiovascular Death with Use of Clarithromycin and Roxithromycin : A Nationwide Cohort Study

Inghammar, Malin LU ; Nibell, Olof LU ; Pasternak, Björn LU ; Melbye, Mads ; Svanström, Henrik and Hviid, Anders (2018) In American Journal of Epidemiology 187(4). p.777-785
Abstract

Recent studies have raised concern that macrolide antibiotics may be associated with an increased long-term risk of cardiovascular death. We examined the 1-year risk associated with treatment with clarithromycin (n = 187,887) or roxithromycin (n = 698,899) compared with penicillin V (n = 3,473,081) matched 1:4 on propensity score, in a nationwide, registry-based cohort study in Danish outpatients, 1997-2011. Among clarithromycin courses, the rate ratio for cardiovascular death was 1.24 (95% confidence interval (CI): 0.96, 1.59). Among roxithromycin courses, the rate ratio was 0.99 (95% CI: 0.86, 1.16). In analyses by time after treatment start, the rate ratio associated with clarithromycin was 1.66 (95% CI: 0.98, 2.79) during days 0-7.... (More)

Recent studies have raised concern that macrolide antibiotics may be associated with an increased long-term risk of cardiovascular death. We examined the 1-year risk associated with treatment with clarithromycin (n = 187,887) or roxithromycin (n = 698,899) compared with penicillin V (n = 3,473,081) matched 1:4 on propensity score, in a nationwide, registry-based cohort study in Danish outpatients, 1997-2011. Among clarithromycin courses, the rate ratio for cardiovascular death was 1.24 (95% confidence interval (CI): 0.96, 1.59). Among roxithromycin courses, the rate ratio was 0.99 (95% CI: 0.86, 1.16). In analyses by time after treatment start, the rate ratio associated with clarithromycin was 1.66 (95% CI: 0.98, 2.79) during days 0-7. This was attenuated in later time periods (days 8-89, rate ratio = 1.30, 95% CI: 0.88, 1.94; and days 90-364, rate ratio = 0.96, 95% CI: 0.63, 1.47). For roxithromycin, the rate ratios were 0.88 (95% CI: 0.59, 1.32) during days 0-7, 1.17 (95% CI: 0.92, 1.48) during days 8-89, and 0.88 (95% CI: 0.70, 1.10) during days 90-364. We found no increased risk of cardiovascular death in a general outpatient population. With clarithromycin, we observed a transient increased risk during days 0-7 after treatment start, which corresponds to the period of active treatment. This association was absent in later time periods, which is consistent with no long-term toxicity resulting in cardiovascular death.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cardiovascular death, clarithromycin, epidemiology, macrolides, roxithromycin
in
American Journal of Epidemiology
volume
187
issue
4
pages
9 pages
publisher
Oxford University Press
external identifiers
  • pmid:29155931
  • scopus:85044758663
ISSN
0002-9262
DOI
10.1093/aje/kwx359
project
Drug-induced liver injuries caused by antimicrobials: Incidence and etiology based on Swedish population data
language
English
LU publication?
yes
id
c27238c3-0e72-4834-824b-4c68facd4d66
date added to LUP
2018-05-23 10:57:00
date last changed
2021-10-06 05:22:10
@article{c27238c3-0e72-4834-824b-4c68facd4d66,
  abstract     = {<p>Recent studies have raised concern that macrolide antibiotics may be associated with an increased long-term risk of cardiovascular death. We examined the 1-year risk associated with treatment with clarithromycin (n = 187,887) or roxithromycin (n = 698,899) compared with penicillin V (n = 3,473,081) matched 1:4 on propensity score, in a nationwide, registry-based cohort study in Danish outpatients, 1997-2011. Among clarithromycin courses, the rate ratio for cardiovascular death was 1.24 (95% confidence interval (CI): 0.96, 1.59). Among roxithromycin courses, the rate ratio was 0.99 (95% CI: 0.86, 1.16). In analyses by time after treatment start, the rate ratio associated with clarithromycin was 1.66 (95% CI: 0.98, 2.79) during days 0-7. This was attenuated in later time periods (days 8-89, rate ratio = 1.30, 95% CI: 0.88, 1.94; and days 90-364, rate ratio = 0.96, 95% CI: 0.63, 1.47). For roxithromycin, the rate ratios were 0.88 (95% CI: 0.59, 1.32) during days 0-7, 1.17 (95% CI: 0.92, 1.48) during days 8-89, and 0.88 (95% CI: 0.70, 1.10) during days 90-364. We found no increased risk of cardiovascular death in a general outpatient population. With clarithromycin, we observed a transient increased risk during days 0-7 after treatment start, which corresponds to the period of active treatment. This association was absent in later time periods, which is consistent with no long-term toxicity resulting in cardiovascular death.</p>},
  author       = {Inghammar, Malin and Nibell, Olof and Pasternak, Björn and Melbye, Mads and Svanström, Henrik and Hviid, Anders},
  issn         = {0002-9262},
  language     = {eng},
  month        = {04},
  number       = {4},
  pages        = {777--785},
  publisher    = {Oxford University Press},
  series       = {American Journal of Epidemiology},
  title        = {Long-Term Risk of Cardiovascular Death with Use of Clarithromycin and Roxithromycin : A Nationwide Cohort Study},
  url          = {http://dx.doi.org/10.1093/aje/kwx359},
  doi          = {10.1093/aje/kwx359},
  volume       = {187},
  year         = {2018},
}