[Researcher Comment] Fluoroquinolones significantly increase risk of serious arrhythmias

Image: PD

Study author, Dr. Samy Suissa, PhD, talks to 2 Minute Medicine: Centre for Clinical Epidemiology, Jewish General Hospital, Montreal Quebec.

“Before our study, no study evaluated whether different fluoroquinolones carry different risks of cardiac rhythm disorders. Our large population-based study of over 600,000 patients found that the risk of serious arrhythmia is elevated with the use of all fluoroquinolones and that the risk is somewhat higher when a new treatment is started. This risk increase was particularly high with gatifloxacin”

Key study points:

1.  Fluoroquinolone use was associated with significantly increased risk of ventricular arrhythmias and death.

2.  The risk of arrhythmia varied between drugs and was greatest with gatifloxacin.

Primer: Fluoroquinolones are a class of antibiotics popular for their broad spectrum of activity and high oral bioavailability.  They are commonly used in both the outpatient and inpatient settings for respiratory, intra-abdominal and urinary tract infections.  Prior clinical trials and drug surveys have suggested the quinolone use is associated with a prolongation of the QTc interval and arrhythmias including torsades de pointes.  The phenomenon of quinolone-associated QT prolongation has been attributed to disruption of potassium channels that regulate the action potential of cardiac myocytes.  This study is the first population-based study assessing the risk of arrhythmia from quinolones that accounts for multiple confounders and examines each individual drug within the class.

Background reading:

1. Clinical use of the fluoroquinolones.

2. Cardiovascular and metabolic safety profiles of the fluoroquinolones.

3. Antimicrobial Safety: Focus on Fluoroquinolones.

This [nested case control] study: drew from medical record databases of all 7 million residents of Quebec.  Cases of ‘serious arrhythmia’ (defined as ventricular arrhythmia or sudden death) were selected from a cohort of 605,127 patients who had received a prescription for respiratory drugs and had no history of arrhythmias.  Up to 20 controls were selected for each case from the same cohort.  Adjusting for confounders and risk factors associated with arrhythmias, the authors calculated rate ratios (RR) using the incidence of serious arrhythmias within each group.  Analysis revealed that all quinolones were associated with a significantly increased risk of serious arrhythmia.  Gatifloxacin showed the highest increased risk with RR of 7.31 (95% CI 2.35 – 23.70).

In sum: This study reinforces prior evidence suggesting an association between quinolone use and serious arrhythmia and also identifies variations of this effect between the different drugs.  The limitations of this study include the inability to clinically validate the diagnosis of the arrhythmia, and the fact that case control studies are always subject to bias and confounding.  Given the increased use of quinolones, the results from this study might provide guidance in drug selection for a patient with significant risk factors for arrhythmias.

Click to read the study in CID

By [AS] and [MS]

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