Oral fluoroquinolone therapy to treat a respiratory infection is associated with an increased risk of sudden cardiac death (SCD) in patients on hemodialysis, particularly those taking other QT-prolonging medications, a large observational study suggests.
However, in many cases, the absolute risk is relatively small, and the antimicrobial benefits of a fluoroquinolone may outweigh the potential cardiac risks, the researchers say.
“Pathogen-directed treatment of respiratory infections is of the utmost importance. Respiratory fluoroquinolones should be prescribed whenever an amoxicillin-based antibiotic offers suboptimal antimicrobial coverage and clinicians should consider electrocardiographic monitoring,” first author Magdalene M. Assimon, PharmD, PhD, University of North Carolina School of Medicine, Chapel Hill, told theheart.org | Medscape Cardiology.
The study was published online October 20 in JAMA Cardiology.
Nearly Twofold Increased Risk
The QT interval-prolonging potential of fluoroquinolone antibiotics are well known. However, evidence linking respiratory fluoroquinolones to adverse cardiac outcomes in the hemodialysis population is limited.
These new observational findings are based on a total of 626,322 antibiotic treatment episodes among 264,968 adults (mean age, 61 years; 51% men) receiving in-center hemodialysis — with respiratory fluoroquinolone making up 40.2% of treatment episodes and amoxicillin-based antibiotic treatment episodes making up 59.8%.
The rate of SCD within 5 days of outpatient initiation of a study antibiotic was 105.7 per 100,000 people prescribed a respiratory fluoroquinolone (levofloxacin or moxifloxacin) versus with 40.0 per 100,000 prescribed amoxicillin or amoxicillin with clavulanic acid (weighted hazard ratio [HR]: 1.95; 95% CI, 1.57 – 2.41).
The authors estimate that one additional SCD would occur during a 5-day follow-up period for every 2273 respiratory fluoroquinolone treatment episodes. Consistent associations were seen when follow-up was extended to 7, 10, and 14 days.
“Our data suggest that curtailing respiratory fluoroquinolone prescribing may be one actionable strategy to mitigate SCD risk in the hemodialysis population. However, the associated absolute risk reduction would be relatively small,” write the authors.
They note that the rate of SCD in the hemodialysis population exceeds that of the general population by more than 20-fold. Most patients undergoing hemodialysis have a least one risk factor for drug-induced QT interval prolongation.
In the current study, nearly 20% of hemodialysis patients prescribed a respiratory fluoroquinolone were taking other medications with known risk for torsades de pointes.
“Our results emphasize the importance of performing a thorough medication review and considering pharmacodynamic drug interactions before prescribing new drug therapies for any condition,” Assimon and colleagues advise.
They suggest clinicians consider electrocardiographic monitoring before and during fluoroquinolone therapy in hemodialysis patients, especially in high-risk individuals.
Reached for comment, Ankur Shah, MD, Division of Kidney Diseases and Hypertension, Warren Alpert Medical School of Brown University, Providence, Rhode Island, called the analysis “valuable” and said the results are “consistent with the known association of cardiac arrhythmias with respiratory fluoroquinolone use in the general population, postulated to be due to increased risk of torsades de pointes from QTc prolongation. This abnormal heart rhythm can lead to sudden cardiac death.”
“Notably, the population receiving respiratory fluoroquinolones had a higher incidence of cardiac disease at baseline, but the risk persisted after adjustment for this increased burden of comorbidity,” Shah told theheart.org | Medscape Cardiology. He was not involved in the current research.
Shah cautioned that observational data such as these should be considered more “hypothesis-generating than practice-changing, as there may be unrecognized confounders or differences in the population that received the respiratory fluoroquinolones.
“A prospective randomized trial would provide a definitive answer, but in the interim, caution should be taken in using respiratory fluoroquinolones when local bacterial resistance patterns or patient-specific data offer another option,” Shah concluded.
Assimon reported receiving grants from the Renal Research Institute (a subsidiary of Fresenius Medical Care), honoraria from the International Society of Nephrology for serving as a statistical reviewer for Kidney International Reports, and honoraria from the American Society of Nephrology for serving as an editorial fellow for the Journal of the American Society of Nephrology. Shah has disclosed no relevant financial relationships.
JAMA Cardiology. Published online October 20, 2021. Abstract