Dataset Information

Risk of aortic aneurysm and aortic dissection with the use of fluoroquinolones in Korea: a nested case-control study.

ABSTRACT:

Background

Recent studies have raised concern about the association of fluoroquinolones with an increased risk of aortic aneurysm and aortic dissection. We aimed to evaluate such risk in a Korean population.

Methods

We conducted a nested case-control study using data from the National Health Insurance Service collected from 2013 to 2017 in Korea. The study cohort included patients older than 40 years and excluded patients who had used fluoroquinolones or been diagnosed with aortic aneurysm, aortic dissection, or related diseases 1 year prior to the cohort entry date. We randomly matched four controls in the risk set with each case of aortic aneurysm and aortic dissection (same sex, age, and cohort entry date). We assessed the risk of aortic aneurysm and aortic dissection from fluoroquinolones and adjusted for potential confounders using a conditional logistic regression model.

Results

A total of 29,638 aortic aneurysm and aortic dissection patients were identified between 2014 and 2017. The use of fluoroquinolones within a year was associated with a 10% increased risk of aortic aneurysm and aortic dissection (adjusted odds ratio: 1.10, 95% CI 1.07-1.14, p < 0.05) compared with nonusers. The risk was higher in patients who had used fluoroquinolones within 60 days (adjusted odds ratio: 1.53, 95% CI 1.46-1.62, p < 0.05). The risk of aortic aneurysm and aortic dissection positively correlated with the cumulative dose and duration of fluoroquinolone therapy (p < 0.001).

Conclusions

Our study provides real-world evidence of the risk of aortic aneurysm and aortic dissection from fluoroquinolones in Korea. Patients and medical professionals should be aware that fluoroquinolones can increase the risk of aortic aneurysm and aortic dissection, which may be acerbated by high dosage and duration of use.

SUBMITTER: Son N

PROVIDER: S-EPMC8842902 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Publications

Risk of aortic aneurysm and aortic dissection with the use of fluoroquinolones in Korea: a nested case-control study.

Son Nayeong N Choi Eunmi E Chung Soo Youn SY Han Soon Young SY Kim Bonggi B

BMC cardiovascular disorders 20220213 1

<h4>Background</h4>Recent studies have raised concern about the association of fluoroquinolones with an increased risk of aortic aneurysm and aortic dissection. We aimed to evaluate such risk in a Korean population.<h4>Methods</h4>We conducted a nested case-control study using data from the National Health Insurance Service collected from 2013 to 2017 in Korea. The study cohort included patients older than 40 years and excluded patients who had used fluoroquinolones or been diagnosed with aortic ...[more]

PMID: 35152888

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Project description:ImportancePrior observational studies have suggested that fluoroquinolone use may be associated with more than 2-fold increased risk of aortic aneurysm or aortic dissection (AA/AD). These studies, however, did not fully consider the role of coexisting infections and the risk of fluoroquinolones relative to other antibiotics.ObjectiveTo estimate the risk of AA/AD associated with infections and to assess the comparative risk of AA/AD associated with fluoroquinolones vs other antibiotics with similar indication profiles among patients with the same types of infections.Designs, settings, and participantsThis nested case-control study identified 21 651 176 adult patients from a nationwide population-based health insurance claims database from January 1, 2009, to November 30, 2015. Each incident case of AA/AD was matched with 10 control individuals by age, sex, and follow-up duration in the database using risk-set sampling. Analysis of the data was conducted from April 2019 to March 2020.ExposuresInfections and antibiotic use within a 60-day risk window before the occurrence of AA/AD.Main outcomes and measuresConditional logistic regression was used to estimate the odds ratios (ORs) and 95% CIs comparing infections for which fluoroquinolones are commonly used with no infection within a 60-day risk window before outcome occurrence, adjusting for baseline confounders and concomitant antibiotic use. The adjusted ORs comparing fluoroquinolones with antibiotics with similar indication profiles within patients with indicated infections were also estimated.ResultsA total of 28 948 cases and 289 480 matched controls were included (71.37% male; mean [SD] age, 67.41 [15.03] years). Among these, the adjusted OR of AA/AD for any indicated infections was 1.73 (95% CI, 1.66-1.81). Septicemia (OR, 3.16; 95% CI, 2.63-3.78) and intra-abdominal infection (OR, 2.99; 95% CI, 2.45-3.65) had the highest increased risk. Fluoroquinolones were not associated with an increased AA/AD risk when compared with combined amoxicillin-clavulanate or combined ampicillin-sulbactam (OR, 1.01; 95% CI, 0.82-1.24) or with extended-spectrum cephalosporins (OR, 0.88; 95% CI, 0.70-1.11) among patients with indicated infections. The null findings for fluoroquinolone use remained robust in different subgroup and sensitivity analyses.Conclusions and relevanceThese results highlight the importance of accounting for coexisting infections while examining the safety of antibiotics using real-world data; the findings suggest that concerns about AA/AD risk should not deter fluoroquinolone use for patients with indicated infections.

Project description:ImportancePrevious observational studies have suggested that fluoroquinolones are associated with aortic aneurysm or dissection, but these studies may be subject to confounding by indication or surveillance bias.ObjectiveTo assess the association of fluoroquinolones with risk of aortic aneurysm or aortic dissection (AA/AD) while accounting for potential confounding by fluoroquinolone indication and bias owing to differential surveillance.Design, setting, and participantsIn an observational cohort study using a US commercial claims database, 2 pairwise 1:1 propensity score-matched cohorts were identified: patients aged 50 years or older with a diagnosis of pneumonia 3 days or less before initiating treatment with a fluoroquinolone or azithromycin and patients aged 50 years or older with a urinary tract infection (UTI) diagnosis 3 days or less before initiating a fluoroquinolone or combined trimethoprim and sulfamethoxazole. Hazard ratios (HRs) and 95% CIs were estimated controlling for 85 baseline confounders. In a secondary analysis, patients receiving fluoroquinolones were compared with those receiving amoxicillin, both with and without considering baseline aortic imaging, to address differences in detection of AA/AD before antibiotic use. Data on patients within the database from January 1, 2003, through September 30, 2015, were analyzed. Data analysis was conducted from July 23, 2019, to July 6, 2020.Main outcomes and measuresHospitalization for AA/AD occurring within 60 days following treatment initiation.ResultsAfter propensity score matching, patient characteristics were well balanced, with 279 554 patients (mean [SD] age, 63.66 [10.93] years; 149 976 women [53.6%]) in the pneumonia cohort and 948 364 patients (mean [SD] age, 62.06 [10.33] years; 823 667 women [86.9%]) in the UTI cohort. Initiators of fluoroquinolones (n = 139 772 pairs in the pneumonia cohort and n = 474 182 pairs in the UTI cohort) had an increased rate of AA/AD compared with initiators of azithromycin (HR, 2.57; 95% CI, 1.36-4.86; incidence, 0.03% for fluoroquinolones vs 0.01% for azithromycin) but no increased rate compared with initiators of combined trimethoprim and sulfamethoxazole (HR, 0.99; 95% CI, 0.62-1.57; incidence, <0.01% in both UTI groups). Secondary analysis using amoxicillin as a comparator (n = 3 976 162 pairs) produced results consistent with those from earlier studies (HR, 1.54; 95% CI, 1.33-1.79; incidence, <0.01% in both groups). Requiring baseline imaging in this cohort (n = 542 649 pairs) to address surveillance bias attenuated the increased rate (HR, 1.13; 95% CI, 0.96-1.33; incidence, 0.06% for fluoroquinolones vs 0.05% for amoxicillin).Conclusions and relevanceThe findings of this nationwide cohort study of adults with pneumonia or UTI suggest an increased relative rate of AA/AD associated with fluoroquinolones within the pneumonia cohort but not within the UTI cohort. In both cohorts, the absolute rate of AA/AD appeared to be low (<0.1%). The increased relative rate observed in the pneumonia cohort may be due to residual confounding or surveillance bias.

Project description:BackgroundFluoroquinolones (FQs) are commonly used to treat urinary tract infections (UTIs), but some studies have suggested they may increase the risk of aortic aneurysm or dissection (AA/AD). However, no large-scale international study has thoroughly assessed this risk.MethodsA retrospective cohort study was conducted using a large, distributed network analysis across 14 databases from 5 countries (United States, South Korea, Japan, Taiwan, and Australia). The study included 13,588,837 patients aged 35 or older who initiated systemic fluoroquinolones (FQs) or comparable antibiotics (trimethoprim with or without sulfamethoxazole [TMP] or cephalosporins [CPHs]) for UTI treatment in the outpatient setting between JAN 01, 2010 and DEC 31, 2019. Patients were included if at the index date they had at least 365 days of prior observation and were not hospitalised for any reason on or within 7 days prior to the index date. The primary outcome was AA/AD occurrence within 60 days of exposure, with secondary outcomes examining AA and AD separately. Cox proportional hazards models with 1:1 propensity score (PS) matching were used to estimate the risk, with results calibrated using negative control outcomes. Analyses were subjected to pre-defined study diagnostics, and only those passing all diagnostics were reported. Hazard ratios (HRs) were pooled using Bayesian random-effects meta-analysis.FindingsAmong analyses that passed diagnostics there were 1,954,798 and 1,195,962 propensity-matched pairs for the FQ versus TMP and FQ versus CPH comparisons respectively. For the 60-day follow-up there was no difference in risk of AA/AD between FQ and TMP (absolute rate difference [ARD], 0.21 per 1000 person-year; calibrated HR, 0.91 [95% CI 0.73-1.10]). There was no significant difference in risk for FQ versus CPH (ARD, 0.11 per 1000 person-year; calibrated HR, 1.01 [95% CI 0.82-1.25]).InterpretationThis large-scale study used a rigorous design with objective diagnostics to address bias and confounding. There was no increased risk of AA/AD associated with FQ compared to TMP or CPH in patients treated for UTI in the outpatient setting. As we only examined FQ used to treat UTIs in the outpatient setting, the results may not be generalisable to other indications with different severity.FundingYonsei University College of Medicine, Government-wide R&D Fund project for infectious disease research (GFID), Republic of Korea, National Health and Medical Research Council (NHMRC) Australian Government. Department of Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI), Department of Veterans Affairs, the United States Government.

Project description: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 < .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.

Project description:ImportanceVascular endothelial growth factor pathway inhibitors (VPIs) pose a concern for aortic aneurysm (AA) and aortic dissection (AD), signaling potential vascular disease development.ObjectiveTo investigate VPI-associated AA and AD.Design, setting, and participantsThis case-control study with a nested design used full population data from a national claims database in Taiwan between 2011 and 2019. Eligible participants were aged 20 years or older with kidney, hepatic, gastrointestinal, or pancreatic cancer diagnosed between January 1, 2012, and December 31, 2019. The first cancer diagnosis date was defined as the cohort entry date. Cases were patients who received a diagnosis of AA or AD in hospitalizations or emergency visits between the cohort entry date and December 31, 2019. Controls were matched by ratio (up to 1:5) based on age, sex, cancer type, cohort entry date, and the index date (ie, the first AA or AD event date). Data analysis was performed between January 2022 and December 2023.ExposuresUse of the oral VPIs sorafenib, sunitinib, and pazopanib between cohort entry date and index date.Main outcomes and measuresIn the primary analysis, AA and AD were evaluated compositely, while in the secondary analyses, they were evaluated separately. Adjusted odds ratios (aORs) were calculated using conditional logistic regression to assess the association with VPI use (sorafenib, sunitinib, and pazopanib) considering various VPI exposure windows and cumulative use.ResultsA total of 1461 cases were included (mean [SD] age, 73.0 [12.3] years; 1118 male patients [76.5%]), matched to 7198 controls. AA or AD risk increased with a VPI exposure of 100 days or less before the index date (aOR, 2.10; 95% CI, 1.40-3.15), mainly from VPI-associated AD (aOR, 3.09; 95% CI, 1.77-5.39). Longer VPI duration (68 days or more: aOR, 2.64; 95% CI, 1.66-4.19) and higher cumulative dose (61 or more defined daily doses: aOR, 2.65; 95% CI, 1.66-4.23) increased the risk.Conclusions and relevanceThe use of the 3 study VPIs (sorafenib, sunitinib, and pazopanib) was associated with an increased risk of AA and AD in patients with cancer, essentially all of the risk from VPI-associated AD. Future studies are needed to determine the risk factors of VPI-associated AA and AD, as well as to establish a class effect.

Dataset Information

Risk of aortic aneurysm and aortic dissection with the use of fluoroquinolones in Korea: a nested case-control study.

Background

Methods

Results

Conclusions

Publications

Risk of aortic aneurysm and aortic dissection with the use of fluoroquinolones in Korea: a nested case-control study.

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