Abstract
Aim
Fluoroquinolones have been associated with life-threatening ventricular arrhythmias
and even sudden cardiac death. We aimed to assess the temporal relationship of fluoroquinolone
use and serious arrhythmias via a case-crossover analysis of a large cohort of serious
arrhythmias patients.
Methods
In a national administrative database, we compare the distributions of fluoroquinolone
exposure for the same patient across a 30-day period before the serious arrhythmia
event and 5 randomly selected 30-day periods before the serious arrhythmia event.
Odds ratios (ORs) and 95% Confidence Intervals (CIs) were estimated using conditional
logistic regression analysis.
Results
From a total of 2 million participants, 7657 patients with serious arrhythmias were
identified. Use of fluoroquinolones within the 30-day period before the event was
significantly associated with increased risk for serious arrhythmia (OR:3.03, 95%
CI:2.48, 3.71). The risk association was attenuated, but remained significant after
adjustment for time-varying confounders (OR:1.48, 95% CI:1.18, 1.86). A consistent
increase in risk of serious arrhythmia was observed for all time windows investigated
(7 days, 14 days, 30 days, 60 days and 90 days).
Conclusions
Exposure to fluoroquinolones was substantially associated with serious arrhythmic
events, independent of the temporal proximity of fluoroquinolone prescription.
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to ResuscitationAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Global antibiotic consumption 2000 to 2010: an analysis of national pharmaceutical sales data.Lancet Infect Dis. 2014; 14: 742-750
- The quinolones: past, present, and future.Clin Infect Dis. 2005; 41: S113-S119
- Rates of torsades de pointes associated with ciprofloxacin, ofloxacin, levofloxacin, gatifloxacin, and moxifloxacin.Pharmacother: J Hum Pharmacol Drug Ther. 2001; 21: 1468-1472
- Torsades de pointes associated with fluoroquinolones.Pharmacother: J Hum Pharmacol Drug Ther. 2002; 22: 663-672
- Mechanism of hERG K+ channel blockade by the fluoroquinolone antibiotic moxifloxacin.Br J Pharmacol. 2006; 147: 905-916
- Potassium current antagonist properties and proarrhythmic consequences of quinolone antibiotics.J Pharmacol Exp Ther. 2001; 296: 806-810
- Oral fluoroquinolone use and serious arrhythmia: bi-national cohort study.bmj. 2016; 352: i843
- Effect of macrolide and fluoroquinolone antibacterials on the risk of ventricular arrhythmia and cardiac arrest.Drug Safety. 2009; 32: 159-167
- Fluoroquinolones and the risk of serious arrhythmia: a population-based study.Clin Infect Dis. 2012; 55: 1457-1465
- Risks of cardiac arrhythmia and mortality among patients using new-generation macrolides, fluoroquinolones, and β-Lactam/β-Lactamase Inhibitors: a Taiwanese Nationwide Study.Clin Infect Dis. 2015; 60: 566-577
- Azithromycin and the risk of cardiovascular death.N Engl J Med. 2012; 366: 1881-1890
- Should we use a case-crossover design?.Ann Rev Public Health. 2000; 21: 193-221
- Taiwan’s healthcare report 2010.EPMA J. 2010; 1: 563
- The case-crossover design: a method for studying transient effects on the risk of acute events.Am J Epidemiol. 1991; 133: 144-153
- A new method of classifying prognostic comorbidity in longitudinal studies: development and validation.J Chron Dis. 1987; 40: 373-383
- Exchangeability in the case-crossover design.Int J Epidemiol. 2014; 43: 1645-1655
- The influence of sex and age on ventricular arrhythmia in a population-based registry.Int J Cardiol. 2017; 244: 169-174
- Aging is a primary risk factor for cardiac arrhythmias: disruption of intracellular Ca2+ regulation as a key suspect.Exp Rev Cardiovasc Ther. 2011; 9: 1059-1067
- Sudden cardiac death: epidemiology and risk factors.Nat Rev Cardiol. 2010; 7: 216-225
- Cardiovascular and metabolic safety profiles of the fluoroquinolones.Expert Opin Drug Saf. 2012; 11: 53-69
- Effect of a single oral dose of moxifloxacin (400 mg and 800 mg) on ventricular repolarization in healthy subjects.Clin Pharmacol Ther. 2000; 68: 658-666
- Measuring the effects of supratherapeutic doses of levofloxacin on healthy volunteers using four methods of QT correction and periodic and continuous ECG recordings.J Clin Pharmacol. 2004; 44: 464-473
- Effects of three fluoroquinolones on QT interval in healthy adults after single doses.Clin Pharmacol Ther. 2003; 73: 292-303
- Antimicrobials and the risk of torsades de pointes: the contribution from data mining of the US FDA adverse event reporting system.Drug Saf. 2010; 33: 303-314
- Primer: administrative health databases in observational studies of drug effects—advantages and disadvantages.Nat Clin Pract Rheumatol. 2007; 3: 725-732
- Electrophysiologic features of torsades de pointes: insights from a new isolated rabbit heart model.J Cardiovasc Electrophysiol. 1997; 8: 1148-1158
- Interactions of a series of fluoroquinolone antibacterial drugs with the human cardiac K+ channel HERG.Mol Pharmacol. 2001; 59: 122-126
- Cellular basis and mechanism underlying normal and abnormal myocardial repolarization and arrhythmogenesis.Ann Med. 2004; 36: 5-14
- Fluoroquinolones increase the risk of serious arrhythmias: a systematic review and meta-analysis.Med (Baltimore). 2017; 96: e8273
- Risk of myocardial infarction and stroke after acute infection or vaccination.N Engl J Med. 2004; 351: 2611-2618
- Risk for myocardial infarction and stroke after community-acquired bacteremia: a 20-year population-based cohort study.Circulation. 2014; 129: 1387-1396
- Long-term mortality and major adverse cardiovascular events in sepsis survivors. A Nationwide population-based study.Am J Respir Crit Care Med. 2016; 194: 209-217
- Use of azithromycin and death from cardiovascular causes.N Engl J Med. 2013; 368: 1704-1712
- Air pollution and ST-elevation myocardial infarction: a case-crossover study of the Belgian STEMI registry 2009-2013.Int J Cardiol. 2016; 223: 300-305
Article info
Publication history
Published online: April 25, 2019
Accepted:
April 23,
2019
Received in revised form:
April 10,
2019
Received:
August 12,
2018
Identification
Copyright
© 2019 Elsevier B.V. All rights reserved.
