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Macrolide antibiotics and the risk of ventricular arrhythmia in older adults
Mai H Trac1, Eric McArthur1, Racquel Jandoc1
1Department of Epidemiology and Biostatistics (Trac, Garg), Western University; Lawson Health Research Institute (Trac), London Health Sciences Centre; Institute for Clinical Evaluative Sciences (ICES) Western (McArthur, Jandoc, Dixon, Nash, Garg); Divisions of Clinical Pharmacology (Hackam) and Nephrology (Garg), Department of Medicine, Western University, London, Ont.
Background:
Many respiratory tract infections are treated with macrolide antibiotics. Regulatory agencies warn that these antibiotics increase the risk of ventricular arrhythmia. We examined the 30-day risk of ventricular arrhythmia and all-cause mortality associated with macrolide antibiotics relative to nonmacrolide antibiotics.
Methods:
We conducted a population-based retrospective cohort study involving older adults (age > 65 yr) with a new prescription for an oral macrolide antibiotic (azithromycin, clarithromycin or erythromycin) in Ontario from 2002 to 2013. Our primary outcome was a hospital encounter with ventricular arrhythmia within 30 days after a new prescription. Our secondary outcome was 30-day all-cause mortality. We matched patients 1:1 using propensity scores to patients prescribed nonmacrolide antibiotics (amoxicillin, cefuroxime or levofloxacin). We used conditional logistic regression to measure the association between macrolide exposure and outcomes, and repeated the analysis in 4 subgroups defined by the presence or absence of chronic kidney disease, congestive heart failure, coronary artery disease and concurrent use of a drug known to prolong the QT interval.
Results:
Compared with nonmacrolide antibiotics, macrolide antibiotics were not associated with a higher risk of ventricular arrhythmia (0.03% v. 0.03%; relative risk [RR] 1.06, 95% confidence interval [CI] 0.83-1.36) and were associated with a lower risk of all-cause mortality (0.62% v. 0.76%; RR 0.82, 95% CI 0.78-0.86). These associations were similar in all subgroups.
Interpretation:
Among older adults, macrolide antibiotics were not associated with a higher 30-day risk of ventricular arrhythmia than nonmacrolide antibiotics. These findings suggest that current warnings from the US Food and Drug Administration may be overstated.
Insights
Macrolide antibiotics, used for respiratory infections, were not linked to increased ventricular arrhythmia risk in older adults. These antibiotics were also associated with lower all-cause mortality, challenging current safety warnings.
Area of Science:
- Cardiology
- Infectious Diseases
- Pharmacology
Background:
- Macrolide antibiotics are commonly prescribed for respiratory tract infections.
- Regulatory agencies have issued warnings regarding macrolide use and increased risk of ventricular arrhythmia.
- This study investigated the association between macrolide antibiotics and adverse cardiac events.
Purpose of the Study:
- To evaluate the 30-day risk of ventricular arrhythmia associated with macrolide antibiotics compared to nonmacrolide antibiotics in older adults.
- To assess the 30-day risk of all-cause mortality in patients prescribed macrolide antibiotics versus nonmacrolide antibiotics.
- To examine these risks across subgroups with specific comorbidities.
Main Methods:
- Population-based retrospective cohort study of adults aged over 65 years in Ontario (2002-2013).
- Patients received new oral prescriptions for macrolide (azithromycin, clarithromycin, erythromycin) or nonmacrolide (amoxicillin, cefuroxime, levofloxacin) antibiotics.
- Propensity score matching (1:1) and conditional logistic regression were used to analyze outcomes: 30-day ventricular arrhythmia and all-cause mortality.
Main Results:
- Macrolide antibiotics were not associated with a higher risk of ventricular arrhythmia compared to nonmacrolide antibiotics (RR 1.06, 95% CI 0.83-1.36).
- Macrolide use was associated with a lower risk of all-cause mortality (RR 0.82, 95% CI 0.78-0.86).
- These findings remained consistent across subgroups with chronic kidney disease, congestive heart failure, coronary artery disease, or concurrent QT-prolonging drug use.
Conclusions:
- In older adults, macrolide antibiotics do not appear to increase the 30-day risk of ventricular arrhythmia compared to nonmacrolide alternatives.
- The observed association with lower all-cause mortality warrants further investigation.
- Current regulatory warnings regarding macrolide-associated ventricular arrhythmia risk may be overstated for this population.
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