Association of oral ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin with the risk of serious ventricular arrhythmia: a nationwide cohort study in Korea

Abstract

ObjectiveTo evaluate whether oral ciprofloxacin, levofloxacin, ofloxacin and moxifloxacin increase the risk of ventricular arrhythmia in Korea’s general population.DesignPopulation-based cohort study using administrative claims data on a national scale in Korea.SettingAll primary, secondary and tertiary care settings from 1 January 2015 to 31 December 2015.ParticipantsPatients who were prescribed the relevant study medications at outpatient visits.Primary outcome measuresEach patient group that was prescribed ciprofloxacin, levofloxacin, ofloxacin or moxifloxacin was compared with the group that was prescribed cefixime to assess the risk of serious ventricular arrhythmia (ventricular tachycardia, fibrillation, flutter and cardiac arrest). Using logistic regression analysis with inverse probability of treatment weighting using the propensity score, OR and 95% CI for serious ventricular arrhythmia were calculated for days 1–7 and 8–14 after the patients commenced antibiotic use.ResultsDuring the study period, 4 888 890 patients were prescribed the study medications. They included 1 466 133 ciprofloxacin users, 1 141 961 levofloxacin users, 1 830 786 ofloxacin users, 47 080 moxifloxacin users and 402 930 cefixime users. Between 1 and 7 days after index date, there was no evidence of increased serious ventricular arrhythmia related to the prescription of ciprofloxacin (OR 0.72; 95% CI 0.49 to 1.06) and levofloxacin (OR 0.92; 95% CI 0.66 to 1.29). Ofloxacin had a 59% reduced risk of serious ventricular arrhythmia compared with cefixime during 1–7 days after prescription. Whereas the OR of serious ventricular arrhythmia after the prescription of moxifloxacin was 1.87 (95% CI 1.15 to 3.11) compared with cefixime during 1–7 days after prescription.ConclusionsDuring 1–7 days after prescription, ciprofloxacin and levofloxacin were not associated with increased risk and ofloxacin showed reduced risk of serious ventricular arrhythmia. Moxifloxacin increased the risk of serious ventricular arrhythmia.

Effects of the Fluoroquinolones Moxifloxacin and Levofloxacin on the QT Subintervals: Sex Differences in Ventricular Repolarization

“…The literature indicates that of all the available fluoroquinolones, moxifloxacin carries the greatest risk of QT prolongation. As a result, it is advised that it should be used in caution in patients with predisposing factors for TdP …”

Serious cardiovascular adverse events with fluoroquinolones versus other antibiotics: A self‐controlled case series analysis

“…Chou and colleagues conducted a similar study using the Taiwan National Health Insurance database and found increased odds of VenA with FQs as a group vs amoxicillin‐clavulanate (aOR 2.07; 95%CI 1.56‐2.76); however, when they evaluated the FQs individually, only moxifloxacin was associated with increased odds of VenA compared with amoxicillin‐clavulanate (aOR 3.3; 95%CI 2.07‐5.25) 8 . In another study of national data from Korea, similar findings were observed; namely, only moxifloxacin was associated with increased odds of VenA compared with cefixime (aOR 1.87; 95%CI 1.15‐3.11) 18 . Conversely, Inghammar et al used propensity score matching with many variables and found no increased incidence of serious arrhythmias with FQs vs penicillin VK (RR 0.85; 95%CI 0.61‐1.18) 19 .…”

“…In another study of national data from Korea, similar findings were observed; namely, only moxifloxacin was associated with increased odds of VenA compared with cefixime (aOR 1.87; 95%CI 1.15-3.11) 18. Conversely, Inghammar et al used propensity score matching with many variables and found no increased incidence of serious arrhythmias with FQs vs penicillin VK (RR 0.85; 95%CI 0.61-1.18) 19.…”

“…However, a large study of Medicare beneficiaries, that was not part of the meta‐analysis, did not find an association between levofloxacin and AMI after adjusting for a wide range of potential confounders 10 . For the outcome of VenA, results published in the literature comparing FQs with other antibiotics have also been mixed 8,9,18,19 . In the previously mentioned cohort study in Veterans by Rao et al, the authors found an increased hazard of serious VenA with levofloxacin vs amoxicillin at treatment days 1‐5 (HR 2.43; 95%CI 1.56‐3.79) and 6‐10 (HR 1.75; 95%CI 1.09‐2.82) 9 .…”

“…10 For the outcome of VenA, results published in the literature comparing FQs with other antibiotics have also been mixed. 8,9,18,19 In the previously mentioned cohort study in Veterans Despite the strengths of our design, limitations remain that are inherent with observational studies. Although fixed confounders are controlled for in an SCCSA, and we included important time-varying covariates, residual time-varying confounding is still possible.…”