Association of Fluoroquinolones With the Risk of Aortic Aneurysm or Aortic Dissection

Gopalakrishnan, Chandrasekar; Bykov, Katsiaryna; Fischer, Michael; Connolly, John G.; Gagne, Joshua J.; Fralick, Michael

doi:10.1001/jamainternmed.2020.4199

Cited by 57 publications

(60 citation statements)

References 28 publications

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“…In a previous study, the use of fluoroquinolone was associated with a two-to three-fold higher risk of aortic dissection, with the risk increasing 10 days after fluoroquinolone exposure (1). Recent studies have reported data that support that it is not fluoroquinolone exposure, but other factors that are associated with aortic dissection in patients who receive fluoroquinolone to treat infections (3, 4), however, even those studies could not fully rule out a causal relationship between fluoroquinolones and aortic dissection in certain patients (3,4).…”

Section: Discussionmentioning

confidence: 99%

Vertebral Artery Dissection after Exposure to Levofloxacin: A Report of Two Cases

Harada

Shimizu

2021

Intern. Med.

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Exposure to quinolones is known to be an independent risk factor for aortic dissection; however, the association with vertebral artery dissection remains unclear. We report two cases of vertebral artery dissection that occurred 4 and 8 days after exposure to levofloxacin, respectively. Both patients had risk factors for vertebral artery dissection, and quinolone use could have been avoided. These two cases indicate that quinolone exposure can be a risk factor for vertebral artery dissection. Considering the possible mechanism, it is better to avoid the prescription of quinolones to patients who have insufficient connective tissues to avoid vertebral artery dissection.

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Section: Discussionmentioning

confidence: 99%

Vertebral Artery Dissection after Exposure to Levofloxacin: A Report of Two Cases

Harada

Shimizu

2021

Intern. Med.

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“…По данным популяционного продольного когортного исследования, проведенного в Канаде [12], общий относительный риск развития аневризмы аорты при терапии ФХ у пациентов старше 65 лет составил 2,72 (95% ДИ 2,53-2,93). Существенную роль в более частом развитии нежелательных реакций у лиц старшей возрастной группы играет полиморбидность [7,17].…”

Section: клинико-морфологические формы и факторы риска поражения аорты при терапии фторхинолонамиunclassified

“…Аневризма аорты наиболее часто развивается на фоне атеросклеротического поражения [7,9,[25][26][27], риски которого максимальны у пациентов пожилого и старческого возраста, курящих, пациентов с дислипидемией, генетической предрасположенностью, нарушениями липидного обмена и сердечно-сосудистыми катастрофами в семейном анамнезе [7,21,25,28]. Риск развития аневризмы брюшной аорты значительно выше у курящих пациентов, чем у некурящих [29].…”

Section: клинико-морфологические формы и факторы риска поражения аорты при терапии фторхинолонамиunclassified

“…Например, степень стимуляции экспрессии ММП-2 препаратами группы ФХ ослабляется в ряду: ципрофлоксацин > спарфлоксацин > моксифлоксацин > ломефлоксацин = гатифлоксацин > норфлоксацин. Аналогичный ряд для ММП-9: ципрофлоксацин > норфлоксацин > гатифлоксацин > ломефлоксацин > моксифлоксацин > спарфлоксацин [7].…”

Section: молекулярные механизмы повреждающего влияния фторхинолонов на ткани аортыunclassified

“…Разрыв аневризмы аорты вызывает массивную кровопотерю и в 50-80% случаев приводит к летальному исходу [4]. Частота развития аневризмы и диссекции аорты на фоне терапии ФХ не превышает 0,3% [5][6][7], тем не менее риск их возникновения выше, чем при использовании других антибактериальных средств [8], что обусловливает необходимость детального изучения взаимосвязи между применением препаратов этой группы и развитием поражений аорты.…”

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Fluoroquinolone-Induced Aortic Injury

Изможерова

Попов

Bakhtin

et al. 2021

Bezopasnost' i risk farmakoterapii

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According to clinical studies, the use of ﬂuoroquinolone antibacterial agents is associated with such rare, but serious adverse reactions as aortic injuries. The aim of the study was to analyse scientiﬁc literature data on the risk of aortic injury during ﬂuoroquinolone treatment. The analytical review showed that the risk factors for ﬂuoroquinolone-induced aortic injury are male gender, age over 45 years, underlying aortic disease, as well as smoking and associated atherosclerosis. Clinical and morphological forms of ﬂuoroquinolone-associated aortic injuries include dilatation (aneurysm development), dissection, and rupture. The analysis of data on the association between aortic injuries and the use of most common ﬂuoroquinolones (ciproﬂoxacin, levoﬂoxacin, and moxiﬂoxacin) showed that development of aneurysm and dissection was most often observed for levoﬂoxacin, and least often for ciproﬂoxacin. The mechanism of aortic injury is due to ﬂuoroquinolone-mediated activation of matrix metalloproteinases which damage elastic components of vascular walls, as well as reduction in lysyl oxidase expression and collagen synthesis. The ability of ﬂuoroquinolones to form complexes with magnesium ions reduces the availability of magnesium to the cell enzyme systems, which delays synthesis of extracellular matrix structural proteins, leads to metalloproteinase activation and calciﬁcation of the vascular walls. Prevention, early detection, and timely management of the above-mentioned issues depend on the awareness of diﬀerent medical specialists about the risks of aortic injury associated with the use of ﬂuoroquinolone antibiotics.

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Association Between Fluoroquinolone Use and Hospitalization With Aortic Aneurysm or Aortic Dissection

et al. 2023

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ImportanceFluoroquinolone use has been associated with increased hospitalization with aortic aneurysm or dissection in noninterventional studies, but the reason for this observed association is unclear.ObjectiveTo determine the association between fluoroquinolone use and aortic aneurysm or dissection using multiple study designs and multiple databases to increase the robustness of findings.Design, Setting, and ParticipantsCohort and case-crossover studies were conducted separately in 2 databases of UK primary care records. Clinical Practice Research Datalink Aurum and GOLD primary care records were linked to hospital admissions data. Adults with a systemic fluoroquinolone or cephalosporin prescription between April 1997 and December 2019 were included in the cohort study. Adults hospitalized with aortic aneurysm or dissection within the eligibility period were included in the case-crossover study. Individuals meeting inclusion criteria in the case-crossover study were matched 1:3 to control individuals on age, sex, index date, and clinical practice to adjust for calendar trends in prescribing. Data were analyzed from January to July 2022.ExposuresSystemic fluoroquinolone or comparator antibiotic.Main Outcomes and MeasuresHazard ratios (HRs) were estimated in the cohort study for the association between prescription of fluoroquinolones and hospitalization with aortic aneurysm or dissection using stabilized inverse probability of treatment-weighted Cox regression. Odds ratios (OR) were estimated in the case-crossover study for the association between systemic fluoroquinolone use and hospitalization with aortic aneurysm or dissection using a conditional logistic regression model. Estimates were pooled across databases using fixed-effects meta-analysis.ResultsIn the cohort study, we identified 3 134 121 adults in Aurum (mean [SD] age, 52.5 [20.3] years; 1 969 257 [62.8%] female) and 452 086 in GOLD (mean [SD] age, 53.9 [20.2] years; 286 502 [63.4%] female) who were prescribed fluoroquinolones or cephalosporins. In crude analyses, fluoroquinolone relative to cephalosporin use was associated with increased hospitalization with aortic aneurysm or dissection (pooled HR, 1.28; 95% CI, 1.13-1.44; P &lt; .001) but after adjustment for potential confounders, this association disappeared (pooled adjusted HR, 1.03; 95% CI, 0.91-1.17; P = .65). In the case-crossover study, we identified 84 841 individuals hospitalized with aortic aneurysm or dissection in Aurum (mean [SD] age, 75.5 [10.9]; 23 551 [27.8%] female) and 10 357 in GOLD (mean [SD] age, 75.6 [10.5]; 2809 [27.1%] female). Relative to nonuse, fluoroquinolone use was associated with an increase in hospitalization with aortic aneurysm or dissection, but no association was found relative to other antibiotics (vs cephalosporin pooled OR, 1.05; 95% CI, 0.87-1.27; vs trimethoprim, 0.89; 95% CI, 0.75-1.06; vs co-amoxiclav, 0.98; 95% CI, 0.82-1.18).Conclusions and RelevanceThe results in this study suggest that estimates of association of fluoroquinolones with aortic aneurysm or dissection may be affected by confounding. When such confounding is accounted for, no association was evident, providing reassurance on the safety of fluoroquinolones with respect to aortic aneurysm or dissection.

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Association of Fluoroquinolones With the Risk of Aortic Aneurysm or Aortic Dissection

Cited by 57 publications

References 28 publications

Vertebral Artery Dissection after Exposure to Levofloxacin: A Report of Two Cases

Vertebral Artery Dissection after Exposure to Levofloxacin: A Report of Two Cases

Fluoroquinolone-Induced Aortic Injury

Association Between Fluoroquinolone Use and Hospitalization With Aortic Aneurysm or Aortic Dissection

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