Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study.
Fluoroquinolones and collagen associated severe adverse events: a longitudinal cohort study.
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DOI：
10.1136/bmjopen-2015-010077
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发表时间：
2015-11-18
期刊：
影响因子：
2.9
通讯作者：
Redelmeier DA
中科院分区：
文献类型：
--
作者：
Daneman N;Lu H;Redelmeier DA
氟喹诺酮相关的肌腱断裂是公认的并发症，但其他严重的胶原相关的不良事件也可能。我们的目的是确认氟喹诺酮类药物与肌腱断裂的相关性，阐明氟喹诺酮类药物与视网膜脱离的潜在相关性，并检测氟喹诺酮类药物与主动脉瘤之间的潜在致命相关性。加拿大安大略基于人群的纵向队列研究。随访1997年4月1日至2012年3月31日期间年满65岁的老年人，直至主要结局、死亡或随访结束（2014年3月31日）。氟喹诺酮类药物处方作为随时间变化的协变量进行测量，患者在治疗过程中和治疗后30天内被认为存在风险。 在医院和急诊室诊断的严重胶原相关不良事件，定义为肌腱断裂、视网膜脱离和主动脉瘤。在1 744 360例合格患者中，657 950例（38%）在随访期间接受了至少一种氟喹诺酮类药物，治疗天数为22 380 515天。 患者发生了37338例（2.1%）肌腱断裂、3246例（0.2%）视网膜脱离和18391例（1.1%）主动脉瘤。 与对照组相比，氟喹诺酮治疗期间严重的胶原相关不良事件更常见，包括肌腱断裂（0.82 vs 0.26/100人年，p<0.001），视网膜脱离（0.03 vs 0.02/100人年，p=0.003）和主动脉瘤（0.35 vs 0.13/100人年，p<0.001）。目前使用的氟喹诺酮类药物与肌腱断裂风险增加有关（HR 3.13，95% CI 2.98 - 3.28;调整后HR 2.40，95% CI 2.24 - 2.57）和主动脉瘤风险增加（HR 2.72，95% CI 2.53 - 2.93;校正HR 2.24，95% CI 2.02 - 2.49），其幅度显著大于这些结局与阿莫西林的相关性。视网膜脱离的风险是轻微的（HR 1.28，95% CI 0.99 - 1.65;调整后的HR 1.47，95% CI 1.08 - 2.00），其程度不大于阿莫西林。氟喹诺酮类药物与随后的肌腱断裂有关，也可能导致主动脉瘤。
Fluoroquinolone-associated tendon ruptures are a recognised complication, but other severe collagen-associated adverse events may also be possible. Our objectives were to confirm the association of fluoroquinolones and tendon rupture, to clarify the potential association of fluoroquinolones and retinal detachment, and to test for a potentially lethal association between fluoroquinolones and aortic aneurysms. Population-based longitudinal cohort study in Ontario, Canada. Older adults turning 65 years between April 1 1997 and March 31 2012 were followed until primary outcome, death, or end of follow-up (March 31 2014). Fluoroquinolone prescriptions were measured as a time-varying covariate, with patients considered at risk during and for 30 days following a treatment course. Severe collagen-associated adverse events defined as tendon ruptures, retinal detachments and aortic aneurysms diagnosed in hospital and emergency departments. Among the 1 744 360 eligible patients, 657 950 (38%) received at least one fluoroquinolone during follow-up, amounting to 22 380 515 days of treatment. The patients experienced 37 338 (2.1%) tendon ruptures, 3246 (0.2%) retinal detachments, and 18 391 (1.1%) aortic aneurysms. Severe collagen-associated adverse events were more common during fluoroquinolone treatment than control periods, including tendon ruptures (0.82 vs 0.26/100-person years, p<0.001), retinal detachments (0.03 vs 0.02/100-person-years, p=0.003) and aortic aneurysms (0.35 vs 0.13/100-person-years, p<0.001). Current fluoroquinolones were associated with an increased hazard of tendon rupture (HR 3.13, 95% CI 2.98 to 3.28; adjusted HR 2.40, 95% CI 2.24 to 2.57) and an increased hazard of aortic aneurysms (HR 2.72, 95% CI 2.53 to 2.93; adjusted HR2.24, 95% CI 2.02 to 2.49) that were substantially greater in magnitude than the association of these outcomes with amoxicillin. The hazard of retinal detachment was marginal (HR 1.28, 95% CI 0.99 to 1.65; adjusted HR 1.47, 95% CI 1.08 to 2.00) and not greater in magnitude than that observed with amoxicillin. Fluoroquinolones are associated with subsequent tendon ruptures and may also contribute to aortic aneurysms.