Oral Fluoroquinolone and the Risk of Aortic Dissection

Chien Chang Lee, Meng tse Gabriel Lee, Ronan Hsieh, Lorenzo Porta, Wan Chien Lee, Si Huei Lee, Shy Shin Chang

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Previous studies raised safety concerns on the association between fluoroquinolone treatment and serious collagen disorders, aortic aneurysm and dissection (AA/AD). Objectives: This study sought to evaluate this association via a case-crossover analysis in a large national administrative database. Methods: A case-crossover design was used to compare the distributions of fluoroquinolone exposure for the same patient across a 60-day period before the AA/AD event (hazard period) and 1 randomly selected 60-day period (referent period) between 60 to 180 days before the AA/AD events. In the sensitivity analysis, the authors repeated the main analysis using a 1:5 ratio of hazard period to referent period, to adjust for the effect of time-variant confounders. A disease-risk score–matched time control analysis was performed to investigate the potential time-trend bias. The risks were calculated by a conditional logistic regression model. Results: A total of 1,213 hospitalized AA/AD patients were identified between 2001 and 2011. In the main case-crossover analysis, exposure to fluoroquinolone was more frequent during the hazard periods than during the referent periods (1.6% vs. 0.6%; odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.14 to 6.46). In the sensitivity analysis, after adjustment for infections and co-medications, the risk remains significant (OR: 2.05; 95% CI: 1.13 to 3.71). An increased risk of AA/AD was observed for prolonged exposure to fluoroquinolones (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day exposure). Susceptible period analysis revealed that the use of fluoroquinolone within 60 days was associated with the highest risk of AA/AD. In the case-time-control analysis, there was no evidence that the observed association is due to temporal changes in fluoroquinolone exposure. Conclusions: Exposure to fluoroquinolone was substantially associated with AA/AD. This risk was modified by the duration of fluoroquinolone use and the length of the hazard period.

Original languageEnglish
Pages (from-to)1369-1378
Number of pages10
JournalJournal of the American College of Cardiology
Volume72
Issue number12
DOIs
Publication statusPublished - Sep 18 2018

Fingerprint

Fluoroquinolones
Aortic Aneurysm
Dissection
Odds Ratio
Logistic Models
Confidence Intervals
Cross-Over Studies
Collagen
Demography
Databases
Safety
Infection

Keywords

  • aortic and arterial diseases
  • aortic aneurysm
  • aortic dissection
  • fluoroquinolones

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Oral Fluoroquinolone and the Risk of Aortic Dissection. / Lee, Chien Chang; Lee, Meng tse Gabriel; Hsieh, Ronan; Porta, Lorenzo; Lee, Wan Chien; Lee, Si Huei; Chang, Shy Shin.

In: Journal of the American College of Cardiology, Vol. 72, No. 12, 18.09.2018, p. 1369-1378.

Research output: Contribution to journalArticle

Lee, Chien Chang ; Lee, Meng tse Gabriel ; Hsieh, Ronan ; Porta, Lorenzo ; Lee, Wan Chien ; Lee, Si Huei ; Chang, Shy Shin. / Oral Fluoroquinolone and the Risk of Aortic Dissection. In: Journal of the American College of Cardiology. 2018 ; Vol. 72, No. 12. pp. 1369-1378.
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abstract = "Background: Previous studies raised safety concerns on the association between fluoroquinolone treatment and serious collagen disorders, aortic aneurysm and dissection (AA/AD). Objectives: This study sought to evaluate this association via a case-crossover analysis in a large national administrative database. Methods: A case-crossover design was used to compare the distributions of fluoroquinolone exposure for the same patient across a 60-day period before the AA/AD event (hazard period) and 1 randomly selected 60-day period (referent period) between 60 to 180 days before the AA/AD events. In the sensitivity analysis, the authors repeated the main analysis using a 1:5 ratio of hazard period to referent period, to adjust for the effect of time-variant confounders. A disease-risk score–matched time control analysis was performed to investigate the potential time-trend bias. The risks were calculated by a conditional logistic regression model. Results: A total of 1,213 hospitalized AA/AD patients were identified between 2001 and 2011. In the main case-crossover analysis, exposure to fluoroquinolone was more frequent during the hazard periods than during the referent periods (1.6{\%} vs. 0.6{\%}; odds ratio [OR]: 2.71; 95{\%} confidence interval [CI]: 1.14 to 6.46). In the sensitivity analysis, after adjustment for infections and co-medications, the risk remains significant (OR: 2.05; 95{\%} CI: 1.13 to 3.71). An increased risk of AA/AD was observed for prolonged exposure to fluoroquinolones (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day exposure). Susceptible period analysis revealed that the use of fluoroquinolone within 60 days was associated with the highest risk of AA/AD. In the case-time-control analysis, there was no evidence that the observed association is due to temporal changes in fluoroquinolone exposure. Conclusions: Exposure to fluoroquinolone was substantially associated with AA/AD. This risk was modified by the duration of fluoroquinolone use and the length of the hazard period.",
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AU - Hsieh, Ronan

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AU - Lee, Wan Chien

AU - Lee, Si Huei

AU - Chang, Shy Shin

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N2 - Background: Previous studies raised safety concerns on the association between fluoroquinolone treatment and serious collagen disorders, aortic aneurysm and dissection (AA/AD). Objectives: This study sought to evaluate this association via a case-crossover analysis in a large national administrative database. Methods: A case-crossover design was used to compare the distributions of fluoroquinolone exposure for the same patient across a 60-day period before the AA/AD event (hazard period) and 1 randomly selected 60-day period (referent period) between 60 to 180 days before the AA/AD events. In the sensitivity analysis, the authors repeated the main analysis using a 1:5 ratio of hazard period to referent period, to adjust for the effect of time-variant confounders. A disease-risk score–matched time control analysis was performed to investigate the potential time-trend bias. The risks were calculated by a conditional logistic regression model. Results: A total of 1,213 hospitalized AA/AD patients were identified between 2001 and 2011. In the main case-crossover analysis, exposure to fluoroquinolone was more frequent during the hazard periods than during the referent periods (1.6% vs. 0.6%; odds ratio [OR]: 2.71; 95% confidence interval [CI]: 1.14 to 6.46). In the sensitivity analysis, after adjustment for infections and co-medications, the risk remains significant (OR: 2.05; 95% CI: 1.13 to 3.71). An increased risk of AA/AD was observed for prolonged exposure to fluoroquinolones (OR: 2.41 for 3- to 14-day exposure; OR: 2.83 for >14-day exposure). Susceptible period analysis revealed that the use of fluoroquinolone within 60 days was associated with the highest risk of AA/AD. In the case-time-control analysis, there was no evidence that the observed association is due to temporal changes in fluoroquinolone exposure. Conclusions: Exposure to fluoroquinolone was substantially associated with AA/AD. This risk was modified by the duration of fluoroquinolone use and the length of the hazard period.

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