Author + information
- Received June 19, 2018
- Accepted June 25, 2018
- Published online September 10, 2018.
- Chien-Chang Lee, MD, ScDa,∗ (, )@q_nationaltaiwa@EinsteinHealth,
- Meng-tse Gabriel Lee, PhDa,
- Ronan Hsieh, MDb,
- Lorenzo Porta, MDc,
- Wan-Chien Lee, MSa,
- Si-Huei Lee, MDd,e and
- Shy-Shin Chang, MD, PhDf
- aDepartment of Emergency Medicine, National Taiwan University Hospital, Taipei, Taiwan
- bDepartment of Medicine, Albert Einstein Medical Center, Philadelphia, Pennsylvania
- cDipartimento di Scienze Biomediche e Cliniche, Ospedale “L. Sacco,” Università degli Studi di Milano, Milan, Italy
- dDepartment of Rehabilitation and Physical Medicine, Taipei Veteran General Hospital, Taipei, Taiwan
- eDepartment of Medicine, College of Medicine, National Yang Ming University, Taipei, Taiwan
- fDepartment of Family Medicine, Taipei Medical University Hospital and School of Medicine, Taipei Medical University, Taipei, Taiwan
- ↵∗Address for correspondence:
Dr. Chien-Chang Lee, Department of Emergency Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 100, Taiwan.
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.
This study was partially supported by the Taiwan National Ministry of Science and Technology Grants MOST 104-2314-B-002 -039 -MY3; MOST 106-2811-B-002-048 and MOST 107-2314-B-002-196 and National Taiwan University Hospital Grant NTUH.106-P04; NTUH.107-P03 and NTUH107-S3892. The sponsors had no influence on the submitted work. The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received June 19, 2018.
- Accepted June 25, 2018.
- 2018 American College of Cardiology Foundation
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