Risk Evaluation of Azithromycin-Induced QT Prolongation in Real-World Practice

Abstract

Background Azithromycin exposure has been reported to increase the risk of QT prolongation and cardiovascular death. However, findings on the association between azithromycin and cardiovascular death are controversial, and azithromycin is still used in actual practice. Additionally, quantitative assessments of risk have not been performed, including the risk of QT prolongation when patients are exposed to azithromycin in a real-world clinical setting. Therefore, in this study, we aimed to evaluate the risk of exposure to azithromycin on QT prolongation in a real-world clinical setting using a 21-year medical history database of a tertiary medical institution. Methods We analyzed the electrocardiogram results and relevant electronic health records of 402,607 subjects in a tertiary teaching hospital in Korea from 1996 to 2015. To evaluate the risk of QT prolongation of azithromycin, we conducted a case-control analysis using amoxicillin for comparison. Multiple logistic regression analysis was performed to correct for age, sex, accompanying drugs, and disease. Results The odds ratio (OR) for QT prolongation (QTc>450 ms in male and >460 ms in female) on azithromycin exposure was 1.40 (95% confidence interval [CI], 1.23-1.59), and the OR for severe QT prolongation (QTc>500 ms) was 1.43 (95% CI, 1.13-1.82). On the other hand, the ORs on exposure to amoxicillin were 1.06 (95% CI, 0.97-1.15) and 0.88 (95% CI, 0.70-1.09). In a subgroup analysis, the risk of QT prolongation in patients aged between 60 and 80 years was significantly higher when they are exposed to azithromycin. Conclusions The risk of QT prolongation was increased when patients, particularly the elderly aged 60-79 years, were exposed to azithromycin. Therefore, clinicians should pay exercise caution using azithromycin or consider using other antibiotics, such as amoxicillin, instead of azithromycin.

American College of Rheumatology Guidance for the Management of Rheumatic Disease in Adult Patients During the COVID‐19 Pandemic: Version 1

“…The panel acknowledged, however, the need for surveillance accompanying HCQ/ CQ administration in hospitalized patients, based on rare reports of cardiotoxicity. Cardiotoxicity risk may be heightened in the context of myocardial injury (reported with COVID-19 [64]) and/ or coadministration of other drugs, such as azithromycin, that are known to prolong the QT interval (65,66).…”

Recommendations for the measurement of the QT interval during the use of drugs for COVID-19 infection treatment. Updatable in accordance with the availability of new evidence

“…LAHRS in collaboration with the Colombian College of Electrophysiology and the Argentine, Brazilian, and Mexican Societies of Cardiac Electrophysiology (SADEC, SOBRAC, SOMEEC) wish to contribute to the mitigation of the risk of occurrence of this type of arrhythmias by the elaboration of this practical document on how to measure the QT interval, their normal values and ranges in which there is true risk associated with QT prolongation [2][3][4] in order to help identify not only patients with long QT at baseline but also those at risk of further abnormal prolongation in response to the initiation of therapy for COVID-19 [5][6][7] (Table 1). In addition, the algorithm recently proposed by the Mayo Clinic [8] for decision-making during the use of hydroxychloroquine and azithromycin has been adapted in patients with COVID-19, with respect to QTc ( Table 2).…”

COVID-19: Present and Future Challenges for Dental Practice

“…However, a number of side effects have been identified especially with intravenous administration, which may be associated with gastrointestinal disturbances, ototoxicity, and pain and inflammation of the injection site [14] The development of resistant bacteria, [15] and its association with proarrhythmic events [16] have also been reported. The latter risk has been attributed to QT prolongation (summation of action potential of ventricular myocytes), which can lead to a life-threatening arrhythmia; however, susceptible patients usually have other co-factors such as old age, heart disease, and exposure to other QT prolonging drugs [17].…”