Observational Study Design Challenges—The Case of Fluoroquinolones and Aortic Disease

DeGette, Raphaela Lipinsky; Grant, Richard W.

doi:10.1001/jamainternmed.2020.4191

Cited by 7 publications

(7 citation statements)

References 4 publications

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“…Baseline characteristics were well balanced after PS matching between treatment groups. Our results reflect the importance of selecting appropriate comparison groups when examining safety issues of antibiotics in real‐world settings 13 . Our results also provide further safety information for individual fluoroquinolones in different follow‐up windows.…”

Section: Discussionsupporting

confidence: 59%

“…Several epidemiological studies suggested that use of fluoroquinolones may precipitate potentially fatal aortic aneurysm or aortic dissection (AA/AD) events, possibly through a collagen degradation pathway 6–10 . However, whether the harmful effect observed is in line with biological mechanisms or due to methodological flaws (e.g., confounding by infection and surveillance bias) remains debated 11–13 …”

mentioning

confidence: 99%

“…[6][7][8][9][10] However, whether the harmful effect observed is in line with biological mechanisms or due to methodological flaws (e.g., confounding by infection and surveillance bias) remains debated. [11][12][13] One recent in vitro study further suggested that fluoroquinolones might damage the integrity of collagen in the heart valves. 14 However, the few real-world studies that have examined the association between fluoroquinolones and heart valvular diseases have produced inconsistent findings.…”

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confidence: 99%

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Association Between Use of Fluoroquinolones and Risk of Mitral or Aortic Valve Regurgitation: A Nationwide Cohort Study

Dong,

Wang,

Chang

et al. 2023

Clin Pharma and Therapeutics

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Biological plausibility suggests that fluoroquinolones may lead to mitral valve regurgitation or aortic valve regurgitation (MR/AR) through a collagen degradation pathway. However, available real‐world studies were limited and yielded inconsistent findings. We estimated the risk of MR/AR associated with fluoroquinolones compared with other antibiotics with similar indications in a population‐based cohort study. We identified adult patients who initiated fluoroquinolones or comparison antibiotics from the nationwide Taiwanese claims database. Patients were followed for up to 60 days after cohort entry. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of MR/AR comparing fluoroquinolones to comparison antibiotics after 1:1 propensity score (PS) matching. All analyses were conducted by type of fluoroquinolone (fluoroquinolones as a class, respiratory fluoroquinolones, and non‐respiratory fluoroquinolones) and comparison antibiotic (amoxicillin/clavulanate or ampicillin/sulbactam, extended‐spectrum cephalosporins). Among 6,649,284 eligible patients, the crude incidence rates of MR/AR ranged from 1.44 to 4.99 per 1,000 person‐years across different types of fluoroquinolones and comparison antibiotics. However, fluoroquinolone use was not associated with an increased risk in each pairwise PS‐matched comparison. HRs were 1.00 (95% CI, 0.89–1.11) for fluoroquinolones as a class, 0.96 (95% CI, 0.83–1.12) for respiratory fluoroquinolones, and 0.87 (95% CI, 0.75–1.01) for non‐respiratory fluoroquinolones, compared with amoxicillin/clavulanate or ampicillin/sulbactam. Results were similar when fluoroquinolones were compared with extended‐spectrum cephalosporins (HRs of 0.96, 95% CI, 0.82–1.12, HR, 1.05, 95% CI, 0.86–1.28, and HR, 0.88, 95% CI, 0.75–1.03, respectively). This large‐scale cohort study did not find a higher risk of MR/AR with different types of fluoroquinolones in the adult population.

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Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 99%

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confidence: 99%

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Association Between Use of Fluoroquinolones and Risk of Mitral or Aortic Valve Regurgitation: A Nationwide Cohort Study

Dong,

Wang,

Chang

et al. 2023

Clin Pharma and Therapeutics

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“…Consistently, without aortic disease history, short-term ciprofloxacin prophylaxis after prostate biopsy did not increase the overall risk of aortic aneurysm or rupture, however, a significantly increased risk of aortic aneurysm was noted in patients with high-risk prostate cancer most likely due to detection bias by more frequent imaging in these patients [ 186 , 187 ]. These studies raised critical concerns about confounding or surveillance bias in previous studies, and consequently, whether FQ triggers de novo aortopathy remains unclear, leaving the uncertainty to physicians for prescribing FQ to patients [ 188 ].…”

Section: Introductionmentioning

confidence: 99%

Risk Factors for Thoracic Aortic Dissection

Zhou

Cecchi

Prakash

et al. 2022

Genes

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Thoracic aortic aneurysms involving the root and/or the ascending aorta enlarge over time until an acute tear in the intimal layer leads to a highly fatal condition, an acute aortic dissection (AAD). These Stanford type A AADs, in which the tear occurs above the sinotubular junction, leading to the formation of a false lumen in the aortic wall that may extend to the arch and thoracoabdominal aorta. Type B AADs originate in the descending thoracic aorta just distal to the left subclavian artery. Genetic variants and various environmental conditions that disrupt the aortic wall integrity have been identified that increase the risk for thoracic aortic aneurysms and dissections (TAD). In this review, we discuss the predominant TAD-associated risk factors, focusing primarily on the non-genetic factors, and discuss the underlying mechanisms leading to TAD.

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“…Several studies ( 12 – 17 ) using large administrative datasets found that recent FQs exposure was strongly associated with an increased risk of AAD, but after adjusting for the comparator antibiotics, two recent studies ( 18 , 19 ) did not support this finding. Although a consensus on whether FQ causes de novo aortic disease has not yet been reached ( 20 , 21 ), this potential association has raised several other important clinical questions, particularly regarding whether FQs can precipitate aortic complications in patients with existing aortic disease. It has been shown that FQ exposure could increase the risk of acute aortic dissection or rupture for patients with underlying aortopathy ( 10 , 11 , 22 ).…”

Section: Introductionmentioning

confidence: 99%

Do fluoroquinolones increase aortic aneurysm or dissection incidence and mortality? A systematic review and meta-analysis

Chen

Patterson

Simpson

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveThe aim of this study was to determine the association between fluoroquinolones (FQs) use, the risk of de novo aortic aneurysm or dissection (AAD), and the prognosis of patients with pre-existing AAD.Materials and methodsWe searched PubMed, EMBASE, CENTRAL, Scopus, and Web of Science on 31 March 2022. Observational studies that evaluated the association of FQs with AAD risk in the general population or FQs with the prognosis of patients with preexisting AAD and presented adjusted effect estimates were included. Two reviewers assessed study eligibility, extracted data, and assessed the risk of bias and certainty of evidence using GRADE.ResultsOf the 13 included studies, 11 focused on the association of FQs with de novo AAD incidence, and only one study investigated the association of FQs with the patient with AAD prognosis. FQ use was associated with an increased risk of de novo AAD within 30 days (RR: 1.42; 95% CI: 1.11–1.81; very low certainty) and 60 days (RR: 1.44; 95% CI: 1.26–1.64; low certainty). Specifically, the association was significant when compared with amoxicillin, azithromycin, doxycycline, or no antibiotic use. Furthermore, patients with preexisting AAD exposure to FQ had an increased risk of all-cause mortality (RR: 1.61; 95% CI: 1.50–1.73; moderate certainty) and aortic-specific mortality (RR: 1.80; 95% CI: 1.50–2.15; moderate certainty), compared to the non-exposed FQ group within a 60-day risk period.ConclusionFQs were associated with an increased incidence of AAD in the general population and a higher risk of adverse outcomes in patients with preexisting AAD. Nevertheless, the results may be affected by unmeasured confounding factors. This should be considered by physicians contemplating using FQs in patients with aortic dilation and those at high risk of AAD.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/], identifier [CRD42021230171].

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Observational Study Design Challenges—The Case of Fluoroquinolones and Aortic Disease

Cited by 7 publications

References 4 publications

Association Between Use of Fluoroquinolones and Risk of Mitral or Aortic Valve Regurgitation: A Nationwide Cohort Study

Association Between Use of Fluoroquinolones and Risk of Mitral or Aortic Valve Regurgitation: A Nationwide Cohort Study

Risk Factors for Thoracic Aortic Dissection

Do fluoroquinolones increase aortic aneurysm or dissection incidence and mortality? A systematic review and meta-analysis

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