Key result
Azithromycin significantly prolonged the QTc interval and decreased left ventricular ejection fraction, and adding it to hydroxychloroquine increased the risk of cardiac dysfunction compared to hydroxychloroquine alone.
Why the study?
Controversial cardiac toxicity results from clinical trials and epidemic studies of hydroxychloroquine and azithromycin suggested their cardiotoxicity needed re-evaluation.
Does short-course treatment with azithromycin or hydroxychloroquine plus azithromycin affect cardiac conduction and function in healthy guinea pigs?
Does short-course treatment with azithromycin or hydroxychloroquine plus azithromycin affect cardiac conduction and function in healthy guinea pigs?
p-value: p=<0.05
In a healthy guinea pig model, azithromycin alone or combined with hydroxychloroquine significantly prolongs the QTc interval and impairs left ventricular systolic function, highlighting potential cardiotoxicity risks.
Azithromycin may carry cardiotoxicity risk; human relevance remains untested.
Background In the early stages of the coronavirus disease pandemic, the anti-malarial drug hydroxychloroquine (HCQ) and the antibiotic drug azithromycin (AZM) were widely used as emerging treatments. However, controversial cardiac toxicity results obtained from clinical trials and epidemic studies suggest that the cardiotoxicity of these two drugs should be re-evaluated. In the present study, we aimed to assess the impact of a short course of AZM or HCQ + AZM combination treatment on ECG and cardiac function in healthy guinea pigs. Methods Thirty-two male guinea pigs were randomly divided into four groups: control; AZM; HCQ; and HCQ + AZM groups. At 3, 6, and 9 days after treatment, electrocardiograms (ECGs) and echocardiographic techniques were used to determine important ECG parameters and cardiac functional parameters of the left ventricle (including posterior wall thickness, end systolic/end diastolic volume, ejection fraction, and fractional shortening). Results Although AZM decreased the heart rates of guinea pigs on day 9 (under anesthetized conditions), HCQ + AZM decreased heart rates on days 3, 6, and 9. The corrected QT intervals of guinea pigs after AZM and HCQ + AZM treatments were significantly increased, compared with CON and HCQ treatment respectively, on days 3, 6, and 9. However, QRS complex durations were not significantly different between the groups. AZM significantly decreased left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) on days 3, 6, and 9, whereas HCQ + AZM only decreased LVEF and LVFS on day 9. Posterior wall thickness and of the left ventricle in the diastolic and systolic states were not significantly different between these groups. In addition, compared with CON, AZM and HCQ decreased the EDV. And, in comparison with HCQ treatment, HCQ + AZM treatment increased ESV on day 9. Conclusions According to our study, AZM significantly prolongs the QT interval and damages cardiac function. Moreover, HCQ + AZM treatment increased the risk of cardiac dysfunction compared with HCQ treatment.
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Li et al. (2020) studied Healthy (cardiotoxicity evaluation) (n=32). Azithromycin or Hydroxychloroquine plus Azithromycin vs. Normal saline or Hydroxychloroquine alone was evaluated on QTc interval and left ventricular ejection fraction (p=<0.05). Azithromycin significantly prolonged the QTc interval and decreased left ventricular ejection fraction, and adding it to hydroxychloroquine increased the risk of cardiac dysfunction compared to hydroxychloroquine alone.
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