Impact of Azithromycin on the Predisposition to Cardiac Arrhythmias in Adult Patients: A Systematic Review

Azithromycin is a macrolide antibiotic that can lead to QT interval prolongation, which may trigger ventricular tachycardia, also known as torsades de pointes (TdP), the most common cardiac arrhythmia associated with these drugs. All macrolides are linked to QTc interval prolongation, with apparently higher risk with erythromycin and clarithromycin compared to azithromycin. Macrolides can extend QT and QTc intervals and cause cardiac arrhythmias, including TdP, ventricular tachycardia, and ventricular fibrillation, through their affinity for binding to the delayed rectifier potassium channel, IKr, inducing QT prolongation and risk of TdP. However, it is crucial to assess the risk-benefit ratio of prescribing azithromycin, especially in patients with preexisting cardiovascular disease or taking concomitant medications that prolong the QT interval. The aim of this study is to determine whether azithromycin is genuinely associated with the occurrence of ventricular arrhythmias in adult patients. This systematic review is based on meticulous searching across Medline and Google Scholar databases, analysis of publications, and synthesis of available evidence regarding the risk of arrhythmias with the use of azithromycin. We reviewed 6 articles that met the criteria, including 20.510.653 patients and 66 articles. While some studies suggest an increased risk of ventricular arrhythmias in certain subgroups of patients, others have not found a significant association between azithromycin and these arrhythmias. These discrepancies could be attributed to differences in the definition of arrhythmias, the duration of follow-up, or the characteristics of the groups of patients evaluated. The results point toward the need for a more thorough risk assessment before initiating this antibiotic in adult patients, especially those with known cardiovascular risk factors or those with a history of heart disease. Several risk factors, such as hypokalemia, pre-existing heart conditions, and concomitant use of other QT-prolonging medications, have been identified as increasing vulnerability to macrolide-induced arrhythmias. The results of the systematic review and cohort studies analyzed consistently suggest an association between the use of azithromycin and an increased risk of developing ventricular arrhythmias. This risk appears to be most evident in the elderly, with different studies showing variations in the magnitude of the risk. It is crucial to evaluate the risks and benefits of these antibiotics in each clinical situation, considering the information provided by observational studies and systematic reviews